Methods and compositions for treating metabolic disorders

FIELD OF THE INVENTION

The present invention provides methods and compositions for treating and preventing metabolic disorders and neurodegenerative disorders, including glucose intolerance and diabetes.

INTRODUCTION

Mitochondria are cellular structures that represent the center-state for energy homeostasis, programmed cell death, and intermediary metabolism. Inherited or acquired defects in mitochondria can give rise to disease pathogenesis. For example, mutations in genes encoding mitochondrial proteins collectively constitute the largest class of inborn errors of metabolism. We have previously shown that dysfunction in this organelle can give rise to degenerative diseases, such as type 2 diabetes. Dysfunction in this organelle can accompany neurodegeneration and the aging process itself.

A variety of different pathologic phenotypes can emerge out of a particular point mutation in mitochondrial DNA. Clinical symptoms in congenital mitochondrial diseases often manifest in postmitotic tissues with high energy demands like brain, muscle, optic nerve, and myocardium, but other tissues including endocrine glands, liver, gastrointestinal tract, kidney, and hematopoietic tissue are also involved, again depending in part on the segregation of mitochondria during development, and on the dynamics of mitochondrial turnover over time.

In addition to congenital disorders involving inherited defective mitochondria, acquired mitochondrial dysfunction contributes to diseases, particularly neurodegenerative disorders associated with aging like Parkinson's, Alzheimer's, Huntington's Diseases. The incidence of somatic mutations in mitochondrial DNA rises exponentially with age; diminished respiratory chain activity is found universally in aging people. Mitochondrial dysfunction is also implicated in excitotoxic neuronal injury, such as that associated with seizures or ischemia.

Treatment of diseases involving mitochondrial dysfunction has involved administration of vitamins and cofactors used by particular elements of the mitochondrial respiratory chain. Coenzyme Q (ubiquinone), nicotinamide, riboflavin, carnitine, biotin, and lipoic acid are used in patients with mitochondrial disease, with occasional benefit, especially in disorders directly stemming from primary deficiencies of one of these cofactors. However, while useful in isolated cases, no such metabolic cofactors or vitamins have been shown to have general utility in clinical practice in treating mitochondrial diseases. Similarly, dichloracetic acid (DCA) has been used to treat mitochondrial cytopathies such as MELAS; DCA inhibits lactate formation and is primarily useful in cases of mitochondrial diseases where excessive lactate accumulation itself is contributing to symptoms. However, DCA does not address symptoms related to mitochondrial insufficiency per se and can be toxic to some patients, depending on the underlying molecular defects.

A need remains for compositions and methods for treating disorders or pathophysiology associated with mitochondrial dysfunction or mitochondrial respiratory chain dysfunction in a mammal, including humans. The invention provides such methods and compositions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-B show C2C12 myotubes in a 384-well format. FIG. 1A: myotubes were differentiated in 384-well format with 4 day starvation (2% horse serum). Tube-like structures are shown using anti-myosin heavy-chain and multinucleus with Hoechst stain. FIG. 1B: Distribution of nuclei for myotubules in a single 384-well. Automated cell counting shows consistent seeding density of 5313+/−384 nuclei per well.

FIG. 2 illustrates the schematic overview of gene expression-based high-throughput screening (GE-HTS) technology. mRNA from cell lysates is captured by 384-well plates coated with oligo-dT, and reverse transcribed to synthesize cDNA. Each target gene is assayed by primer pairs, with gene-specific target sequences that bind adjacently on the corresponding cDNA. Primer pairs are ligated only if they are bound to cDNA, such that the number of ligated products is equal to the copy number of the corresponding cDNA. The ligated products are PCR-amplified using universal primer pairs, and captured with an anti-tag sequence selected for each gene. Each anti-tag sequence is attached to colored beads, and the PCR products are stained with streptavidin-phycoerythrin (SAPE). Dual-color flow cytometry detects bead color in order to identify each gene, and quantifies the amount of SAPE fluorescence to quantify transcript levels.

FIG. 3 shows a schematic used for complementary profiles of viability, mitochondrial physiology and gene expression across 2,490 chemical perturbations. The calcein assay (1) measures cell viability and filters out overtly toxic compounds, such as staurosporine. The MTT assay (2) measures cellular dehydrogenase activity, which is inhibited by the complex I inhibitor rotenone. The JC-1 assay (3) measures the mitochondrial membrane potential (ΔΨm) and drops acutely after the addition of the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP). A luciferase-based assay measures ATP (4), which is reduced by staurosporine. CM-H2DCFDA is a fluorescent probe of cellular ROS (5), which can be stimulated by the addition of H2O2. The expression of both nuOXPHOS and mtOXPHOS transcripts is measured by a multiplex PCR technique, GE-HTS (6). Each column of the heat map represents one sample replicate; expression levels for each gene are row-normalized. Treatment with PGC-1α, an inducer of OXPHOS gene expression, is used as a positive control. All assays were performed in biological duplicate in 384-well format after 48 h of treatment in differentiated murine C2C12 myotubes. Data from 2,490 distinct compounds are incorporated into the screening compendium.

FIG. 4 shows two complementary strategies to identify small molecules that boost OXPHOS gene expression and decrease ROS levels. (a) Mining the compendium for sets of structurally related compounds that achieve the desired activity. All compounds were organized into 624 clusters based on the chemical descriptors molecular weight, log P, number of hydrogen bond donors and acceptors, and number of rotatable bonds. The Mann-Whitney rank-sum statistic for each cluster and each assay was then calculated. The significance of each cluster in each assay is shown, with points above zero indicating positive composite scores and points below zero showing negative composite scores. A nominal P=0.01 is delimited by the dashed lines. The black data points spotlight a single cluster that is significant for the desired activity, with the shared chemical scaffold shown. (b) Mining the compendium for individual compounds that achieve the desired activity. The distributions of ROS scores are shown for all compounds (gray) and for compounds associated with the highest OXPHOS gene expression (black). The latter follow a bimodal distribution, and the smaller mode (bracketed) contains six compounds that elevate OXPHOS expression and decrease ROS levels, with chemical structures shown.

FIG. 5 shows how cell-based assays provide complementary information. a, Pairwise correlation coefficients between assays using composite Z-scores for all 2490 compounds tested. b, Pairwise correlation coefficients between all assays using composite Z-scores after filtering for low-signal outliers (p<0.05) in the viability assay.

FIG. 6 shows the secondary analyses of the effects of microtubule inhibitors on OXPHOS gene expression and physiology. (a) Compounds indicated in FIG. 4 were retested at 20 nM, 200 nM, 2 μM and 20 μM. Gene expression levels are represented as a row-normalized heat map, with negative controls (DMSO treatment) and positive controls (PGC-1α treatment) shown. Dose-response curves for ROS levels and viability are also provided, where the y-axis is the composite Z-score. Shaded area indicates the noise envelope (P<0.05). Data shown are the results of four biological replicates per concentration. (b) Analysis of mtDNA/nuDNA copy number ratio after treatment with four of the compounds (deo, deoxysappanone B; meb, mebendazole; noc, nocodazole; pac, paclitaxel), using three biological replicates, normalized to DMSO treatment alone. (c) Quantitative PCR measurement of Ppargc1a gene expression, in response to either DMSO alone (Con), 5 μM deoxysappanone B (deo) or 1 μM mebendazole (meb). (d) Quantitative PCR measurement of the nuclear OXPHOS gene Atp5a1. Cells were either treated with compound alone (black bars) or in combination with 5 mM of the ERRa inverse agonist XCT790 (gray bars). (e) Quantitative PCR measurement of Sod2, which encodes the ROS scavenger MnSOD, as in (d). Means and s.d. of expression data are the result of four biological replicates.

FIG. 7 shows tubulin immunofluorescence after treatment with deoxysappanone B and paclitaxel. C2C12 myotubes were treated with compounds for 48 hours and stained for microtubules using an anti-α-tubulin antibody (green) and nuclei using Hoechst 33342 (blue). Deoxysappanone B treatments: a, none, b, 10 nM, c, 100 nM, d, 1 μM, e, 10 μM. Paclitaxel treatments: f, none, g, 10 nM, h, 100 nM, i, 1 μM, j, 10 μM. Scale bar=50 μm.

FIG. 8 show measurements of the coupling between nuclear and mitochondrial OXPHOS gene expression. (a) A two-dimensional plot of the composite Z-scores for nuOXPHOS and mtOXPHOS expression is shown. (b) Row-normalized heat map displaying the top 15 compounds in each quadrant (I-IV). Heat map of nuOXPHOS and mtOXPHOS expression is shown along with ATP levels. (c) Real-time PCR validation of select compounds at the indicated doses, using Atp5a1 (nuOXPHOS) and mt-Co1 (mtOXPHOS) normalized to Hprt1 (internal control). Values indicate average fold change from mock-treated (DMSO) wells ±s.d. in four biological replicates.

FIG. 9 shows statin-induced mitochondrial toxicity. (a) Six of the HMG-CoA reductase inhibitors (statins) in clinical use are in the chemical screening collection. Composite Z-scores for cell viability, ATP generation, MTT activity, ΔΨm, ROS levels and gene expression are shown, where negative scores indicate a decrease in signal compared to mock-treated (DMSO) wells. The gray shading indicates scores that fall within the noise envelope. (b) A centroid statin score was generated by calculating the arithmetic means of the composite Z-scores for fluvastatin, lovastatin and simvastatin. The ten nearest neighbor clinically used drugs (amoxapine, cyclobenzaprine, propranolol, griseofulvin, pentamidine, paclitaxel, propafenone, ethaverine, trimeprazine and amitriptyline) were identified by calculating the root-mean-square distance of each performance vector to the profile of interest. (c) All six statins were tested in combination with three clinically used b-adrenergic blockers (propranolol, atenolol and metoprolol) for their effects on cellular ATP levels. Compound concentrations are indicated on each axis, and the grayscale intensity indicates the change in ATP levels (ranging from black, for no change, to medium gray, for a 50% decrease). Data represent the average of six independent replicates; coefficients of variation were all below 15%.

FIG. 10 shows the dose-response curves for statins and beta blockers for cellular ATP levels. a, The six statins in our collection were tested in doses as high as 40 μM for 48 hours before ATP levels were measured. The three mitochondrially active statins in the screening compendium are in gray (top to bottom: simvastatin, lovastatin, fluvastatin), while the other three are in black (pravastatin, rosuvastatin, atorvastatin). b, Three beta adrenergic antagonists (one nonselective and two beta₁-selective) were tested in doses as high as 40 μM for 48 hours and then ATP levels were measured. Black line, atenolol; light gray line, metoprolol, both selective antagonists; dark gray line, propranolol, a nonselective antagonist.

SUMMARY OF THE INVENTION

The invention has been comtemplated such that all embodiments described herein, including those embodiments described under different aspects of the invention, can be combined with one another, where appropriate.

One aspect of the invention provides a method of treating or preventing a disorder characterized by mitochondrial dysfunction in a subject, the method comprising administering to the subject a therapeutically effective amount of a cytoskeleton modulator. In some embodiments, the cytoskeleton modulator is a microtubule modulator. In some embodiments, the microtubule modulator is a microtubule inhibitor. In some embodiments, the cytoskeleton modulator is a compound of Formula (I):

wherein R is selected from (C₁-C₄)alkyl, cycloalkyl having 3 to 6 carbon atoms, phenyl, halo-substituted phenyl in which halo in each occurrence is selected from Br, Cl, or F, (lower alkyl)-substituted phenyl, ((C₁-C₄)alkoxy)-substituted phenyl, and 2-thienyl; R¹is selected from methyl and ethyl, X is selected from —S—, —C(O)—, —O—, —CH₂— and —S(O)— and the R—X— substituent is located at the 5(6)-position, or a salt thereof.

In some embodiments, the compound is mebendazole, a derivative, metabolite, or analog thereof. In some embodiments, the compound is mebendazole or a metabolite or analog thereof. In some embodiments, the subject is not afflicted with a worm infection. In some embodiments, the worm infection is a hookworm infection, a roundworm infection, a pinworm infection or a whipworm infection. In some embodiments, wherein the subject is not afflicted with diabetes. In some embodiments, the compound is nocodazole, a derivative, metabolite, or analog thereof.

In some embodiments, the compound is one of the following: albendazole, fenbendazole, oxfendazole, oxibendazole, methiazole, parbendazole, and any derivatives, metabolites, or analogs of the compounds listed.

In some embodiments, the cytoskeleton modulator is cytochalasin, a derivative, metabolite, or analog thereof. In some embodiments, the cytochalasin is selected from cytochalasin A, cytochalasin B, cytochalasin C, cytochalasin D, cytochalasin E, cytochalasin F, cytochalasin H, cytochalasin J, cytochalasin K, cytochalasin Q, cytochalasin R, epoxycytochalasin H and epoxycytochalasin J. In some embodiments, the cytochalasin is selected from cytochalasin E.

In some embodiments, the cytoskeleton modulator is a compound of Formula (II):

wherein R¹is selected from H or methyl and R²is selected from H or hydroxy. In some embodiments, the cytoskeleton modulator is a compound selected from Formulas (III)-(VI):

In some embodiments, the compound is deoxysappanone B, or a metabolite, or an analog thereof.

In some embodiments, the cytoskeleton modulator is a compound of Formula (VII):

wherein, R is nitrogen or acetyl and one of R¹and R²is hydroxy and the other is selected from t-butylcarbonylamino or benzoylamino.

In some embodiments, the compound is paclitaxel or a metabolite or analog thereof. In some embodiments, the compound is podofilox, a metabolite, analog, or salt thereof. In some embodiments, the compound is podophyllotoxin acetate.

In some embodiments, the cytoskeleton modulator is a compound of Formula (VIII):

wherein R¹, R², R³and R⁴are independently selected from H, lower alkyl group, lower alkoxy group, halogen, lower perfluoroalkyl group, lower alkylthio group, hydroxy group, amino group, mono- or di-alkyl or acylamino group, lower alkyl or arylsulfonyloxy group, R⁵is H, or a lower alkyl group or a substituted or non-substituted aryl group, R⁶is an alkyl group of carbon number 4 or less, R¹⁴, R¹⁵and R¹⁶are an alkyl group of carbon number 4 or less, R¹⁷is H or an alkyl group of carbon number 4 or less, and in between carbon 14 and carbon 15 is an unsaturated double bond or saturated bond.

In some embodiments, the compound is vinblastine or a metabolite or analog thereof.

In some embodiments, the compounds described herein can be used to increase glucose uptake in a cell.

In some embodiments, the mitochondrial dysfunction is characterized by reduced oxidative phosphorylation or increased generation of reactive oxygen species or both. In some embodiments, the disorder is diabetes or glucose intolerance. In some embodiments, the disorder is, obesity, cardiac myopathy, premature aging, coronary atherosclerotic heart disease, diabetes mellitus, Alzheimer's Disease, Parkinson's Disease, Huntington's disease, dystonia, Leber's hereditary optic neuropathy (LHON), schizophrenia, myodegenerative disorders such as “mitochondrial encephalopathy, lactic acidosis, and stroke” (MELAS). and “myoclonic epilepsy ragged red fiber syndrome” (MERRF), NARP (Neuropathy; Ataxia; Retinitis Pigmentosa), MNGIE (Myopathy and external opthalmoplegia, neuropathy; gastro-intestinal encephalopathy, Kearns-Sayre disease, Pearson's Syndrome, PEO (Progressive External Opthalmoplegia), congenital muscular dystrophy with mitochondrial structural abnormalities, Wolfram syndrome, Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy Deafness, Leigh's Syndrome, fatal infantile myopathy with severe mitochondrial DNA (mtDNA) depletion, benign “later-onset” myopathy with moderate reduction in mtDNA, dystonia, medium chain acyl-CoA dehydrogenase deficiency, arthritis, and mitochondrial diabetes and deafness (MIDD), mitochondrial DNA depletion syndrome.

In some embodiments, the subject is not afflicted with cancer.

In some embodiments, the disorder is obesity. In some embodiments, the disorder is diabetes. In some embodiments, the diabetes is type 2 diabetes mellitus. In some embodiments, the disorder is glucose intolerance. In some embodiments, the subject has elevated gluconeogenesis. In some embodiments, the disorder is premature aging. In some embodiments, the disorder is a neurodegenerative disorder. In some embodiments, the neurodegenerative disorder is characterized by neuronal cell death. In some embodiments, the neurodegenerative disorder is Parkinson disease, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Huntington's disease or Freidreich's ataxia.

In some embodiments, the disorder is selected from Familial British Dimentia, Finnish-type Familial Amyloidoses, Frontotemporal Dementia, Senile Systemic Amyloidosis, Familial Amyloid Polyneuropathy, Transmissible Spongiform Encephalopathie, Gertsmann-Strausseler-Scheinker Syndrome, Fatal Familial Insomnia, Huntington's Chorea, Kuru, Familial amyloid polyneuropathy, Creutzfeldt Jakob, Scrapie, and Bovine Spongiform Encephalopathy.

In some embodiments, the disorder is an mtDNA-associated disease. In some embodiments, the mt-DNA associated disease is MERRF, MELAS, LHON, MILASA, MILS, PEO or KSS.

In some embodiments, the disorder is a mitochondrial encephalomyopathy due to nuclear gene mutations. In some embodiments, the encephalomyopathy is Leigh syndrome French Canadian variety, mtDNA depletion syndromes, Barth syndrome and Wilson's disease. In some embodiments, the disorder is a congenital mitochondrial disorder.

In some embodiments, the compound is cytochalasin E or a metabolite or analog thereof. In some embodiments, the compound is deoxysappanone or a metabolite, analog or derivative thereof.

In some embodiments, the deoxysappanone is selected from deoxysappanone (B) 7,3′-dimethyl ether, sappanone (A) trimethyl ether, or 3-deshydroxysappanol trimethyl ether. In some embodiments, the subject is not afflicted with diabetes. In some embodiments, the compound is nocodazole or a metabolite or analog thereof. In some embodiments, the compound is paclitaxel or a metabolite or analog thereof. In some embodiments, the compound is podofilox or a metabolite or analog thereof. In some embodiments, the compound is podophyllotoxin acetate or a metabolite or analog thereof. In some embodiments, the compound is vinblastine or a metabolite or analog thereof.

In some embodiments, the disorder is cardiovascular disease. In some embodiments, the disorder is cardiomyopathy.

In some embodiments, the method of treating or preventing a disorder characterized by mitochondrial dysfunction in a subject further comprises administering to the subject one or more agents selected from sulfonylureas, non-sulfonylurea secretagogues, insulin, insulin analogs, glucagon-like peptides, exendin-4 polypeptides, beta 3 adrenoceptor agonists, PPAR agonists, dipeptidyl peptidase IV inhibitors, biguanides, alpha-glucosidase inhibitors, immunomodulators, statins and statin-containing combinations, angiotensin converting enzyme inhibitors, adeno sine A1 receptor agonists, adenosine A2 receptor agonists, aldosterone antagonists, alpha 1 adrenoceptor antagonists, alpha 2 adrenoceptor agonists, alpha 2 adrenoceptor agonists, angiotensin receptor antagonists, antioxidants, ATPase inhibitors, atrial peptide agonists, beta adrenoceptor antagonists, calcium channel agonists, calcium channel antagonists, diuretics, dopamine D1 receptor agonists, endopeptidase inhibitors, endothelin receptor antagonists, guanylate cyclase stimulants, phosphodiesterase V inhibitors, protein kinase inhibitors, Cdc2 kinase inhibitors, renin inhibitors, thromboxane synthase inhibitors, vasopeptidase inhibitors, vasopressin I antagonists, vasopressin 2 antagonists, angiogenesis inhibitors, advanced glycation end product inhibitors, bile acid binding agents, bile acid transport inhibitors, bone formation stimulants, apolipoprotein A1 agonists, DNA topoisomerase inhibitors, cholesterol absorption inhibitors, cholesterol antagonists, cholesteryl ester transfer protein antagonists, cytokine synthesis inhibitors, DNA polymerase inhibitors, dopamine D2 receptor agonists, endothelin receptor antagonists, growth hormone antagonists, insulin sensitizers, lipase inhibitors, lipid peroxidation inhibitors, lipoprotein A antagonists, microsomal transport protein inhibitors, microsomal triglyceride transfer protein inhibitors, nitric oxide synthase inhibitors, oxidizing agents, phospholipase A2 inhibitors, radical formation agonists, platelet aggregation antagonists, prostaglandin synthase stimulants, reverse cholesterol transport activators, rho kinase inhibitors, selective estrogen receptor modulators, squalene epoxidase inhibitors, squalene synthase inhibitors, thromboxane A2 antagonists, amylin agonists, cannabinoid receptor antagonists, cholecystokinin A agonists, corticotropin-releasing factor agonists, dopamine uptake inhibitors, G protein-coupled receptor modulators, glutamate antagonists, glucagon-like peptide-1 agonists, insulin sensitizers, lipase inhibitors, melanin-concentrating hormone receptor antagonists, nerve growth factor agonists, neuropeptide Y agonists, neuropeptide Y antagonists, SNRIs, protein tyrosine phosphatase inhibitors, serotonin 2C receptor agonists, bezafibrate, diflunisal, or cinnamic acid.

In some embodiments, said sulfonylurea is selected from the group consisting of acetohexamide, chlorpropamide, tolazamide, tolbutamide, glimepiride, glipizide, and glyburide. In some embodiments, said non-sulfonylurea secretagogue is nateglinide or repaglinide. In some embodiments, said insulin analog is selected from the group consisting of insulin lispro, insulin aspart, insulin glarginine, NPH, lente insulin, ultralente insulin, humulin, and novolin. In some embodiments, said PPAR agonist is selected from the group consisting of balaglitazone, troglitazone, pioglitazone, ciglitazone, englitazone, rosiglitazone, darglitazone, englitazone, netoglitazone, KRP-297, JTT-501, NC-2100, NIP-223, MCC-555, L-764486, CS-011, G1262570, GW347845, and FK614. In some embodiments, said biguanide is metformin or metformin/glyburide. In some embodiments, said alpha-glucosidase inhibitor is acarbose or miglitol. In some embodiments, said immunomodulator is a corticosteroid, cyclophosphamide, or NsIDI. In some embodiments, said angiotensin converting enzyme (ACE) inhibitor is selected from the group consisting of benazepril, captopril, cilazapril, enalapril, enalaprilat, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril. In some embodiments, said angiotensin II receptor blocker is selected from the group consisting of candesartan, eprosartan, irbesarten, losartin, telmisartan, and valsartan. In some embodiments, said antioxidant is selected from the group consisting of nicotinamide, vitamin E, probucol, MDL29311, and U78518F. In some embodiments, said exendin 4 is AC2993. In some embodiments, said glucagon-like peptide is GLP-1.

In another aspect of the invention, methods are provided for identifying compounds that enhance mitochondrial function, comprising (i) assaying for the effect of one or more compounds on (a) OXPHOS gene expression and (b) mitochondrial function; and (ii) correlating the effect with a compound's enhancement of mitochondrial function, wherein an increase in OXPHOS gene expression and an increase in mitochondrial function is indicative of a compound that enhances mitochondrial function. In some embodiments, the assay is performed on murine myotubes. In some embodiments, mitochondrial function is assayed by measuring reactive oxygen species (ROS). In some embodiments, an increase in OXPHOS gene expression and a decrease in ROS is indicative of a compound that enhances mitochondrial function. In some embodiments, the method further comprises assaying for the effect of one or more compounds on (c) cell viability, and wherein the lack of a decrease on cell viability is indicative of a compound that enhances mitochondrial function. In some embodiments, cell viability is measured using calcein dye. In some embodiments, comprises assaying for the effect of one or more compounds on one or more of the following: cellular dehydrogenase activity; mitochondrial membrane potential; cellular ATP; and cytochrome c protein.

In some embodiments, OXPHOS gene expression is measured using a gene expression-based high-throughput screening (GE-HTS) assay. In some embodiments, OXPHOS gene expression comprises the expression of the following genes: (a) Mt-Atp6 (Entrez GeneID numbers 17705 or 4508), (b) Mt-Atp8 (Entrez GeneID numbers 17706 or 4509), (c) Mt-Co1 (Entrez GeneID numbers 17708 or 4512), (d) Mt-Co2 (Entrez GeneID numbers 17709 or 4513), (e) Mt-Co3 (Entrez GeneID numbers 17710 or 4514), (f) Mt-Cytb (Entrez GeneID number 17711 or 4519), (g) Mt-Nd1 (Entrez GeneID numbers 17716 or 4535), (h) Mt-Nd2 (Entrez GeneID numbers 17717 or 4536), (i) Mt-Nd3 (Entrez GeneID numbers 17718 or 4537), (j) Mt-Nd4 (Entrez GeneID numbers 17719 or 4538), (k) Mt-Nd41 (Entrez GeneID numbers 17720 or 4539), (l) Mt-Nd5 (Entrez GeneID numbers 17721 or 4540), (m) Mt-Nd6 (Entrez GeneID numbers 17722 or 4541), (n) Atp5a1 (Entrez GeneID numbers 11946 or 498), (o) Atp5c1 (Entrez GeneID numbers 11949 or 509), (p) Atp5o (Entrez GeneID numbers 28080 or 539), (q) Cox5b (Entrez GeneID numbers 12859 or 1329), (r) Cox7a2 (Entrez GeneID numbers 12866 or 1347), (s) Cyc1 (Entrez GeneID numbers 66445 or 1537), (t) Hspc051 (Entrez GeneID number 66152 or 29796), (u) Ndufa5 (Entrez GeneID numbers 68202 or 4698), (v) Ndufb5 (Entrez GeneID numbers 66046 or 4711), (w) Sdhd (Entrez GeneID numbers 66925 or 6392), (x) Uqcrb (Entrez GeneID numbers 67530 or 7381), and (y) Uqcrc1 (Entrez GeneID numbers 22273 or 7384)

In some embodiments, the assays are performed in a multi-well plate format. In some embodiments, the one or more compounds comprise a library of compounds.

In another aspect of the invention, methods are provided for identifying compounds for treating a disorder characterized by mitochondrial dysfunction in a subject comprising (i) assaying for the effect of one or more compounds on (a) OXPHOS gene expression and (b) mitochondrial function; and (ii) correlating the effect with a compound's ability to treat said disorder, wherein an increase in OXPHOS gene expression and an increase in mitochondrial function is indicative of a compound useful for treating said disorder. In some embodiments, mitochondrial function is assayed by measuring reactive oxygen species (ROS). In some embodiments, an increase in OXPHOS gene expression and a decrease in ROS is indicative of a compound that enhances mitochondrial function.

In some embodiments, the method further comprises assaying for the effect of one or more compounds on cell viability, and wherein the lack of a decrease on cell viability is indicative of a compound that enhances mitochondrial function. In some embodiments, cell viability is measured using calcein dye. In some embodiments, the mitochondrial function is assayed by measuring reactive oxygen species (ROS) and further comprises assaying for the effect of one or more compounds on one or more of the following: cellular dehydrogenase activity; mitochondrial membrane potential; cellular ATP; and cytochrome c protein, wherein an increase in cellular dehydrogenase activity, an increase in mitochondrial membrane potential; an increase cellular ATP; and an increase in cytochrome c protein is indicative of a compound that enhances mitochondrial function.

In some embodiments, OXPHOS gene expression is measured using a gene expression-based high-throughput screening (GE-HTS) assay. In some embodiments, OXPHOS gene expression comprises the expression of the following genes: (a) Mt-Atp6 (Entrez GeneID numbers 17705 or 4508), (b) Mt-Atp8 (Entrez GeneID numbers 17706 or 4509), (c) Mt-Co1 (Entrez GeneID numbers 17708 or 4512), (d) Mt-Co2 (Entrez GeneID numbers 17709 or 4513), (e) Mt-Co3 (Entrez GeneID numbers 17710 or 4514), (f) Mt-Cytb (Entrez GeneID number 17711 or 4519), (g) Mt-Nd1 (Entrez GeneID numbers 17716 or 4535), (h) Mt-Nd2 (Entrez GeneID numbers 17717 or 4536), (i) Mt-Nd3 (Entrez GeneID numbers 17718 or 4537), (j) Mt-Nd4 (Entrez GeneID numbers 17719 or 4538), (k) Mt-Nd41 (Entrez GeneID numbers 17720 or 4539), (l) Mt-Nd5 (Entrez GeneID numbers 17721 or 4540), (In) Mt-Nd6 (Entrez GeneID numbers 17722 or 4541), (n) Atp5a1 (Entrez GeneID numbers 11946 or 498), (o) Atp5c1 (Entrez GeneID numbers 11949 or 509), (p) Atp5o (Entrez GeneID numbers 28080 or 539), (q) Cox5b (Entrez GeneID numbers 12859 or 1329), (r) Cox7a2 (Entrez GeneID numbers 12866 or 1347), (s) Cyc1 (Entrez GeneID numbers 66445 or 1537), (t) Hspc051 (Entrez GeneID number 66152 or 29796), (u) Ndufa5 (Entrez GeneID numbers 68202 or 4698), (v) Ndufb5 (Entrez GeneID numbers 66046 or 4711), (w) Sdhd (Entrez GeneID numbers 66925 or 6392), (x) Uqcrb (Entrez GeneID numbers 67530 or 7381), and (y) Uqcrc1 (Entrez GeneID numbers 22273 or 7384)

In some embodiments, the assays are performed in a multi-well plate format. In some embodiments, the one or more compounds comprise a library of compounds.

In some embodiments, the mitochondrial dysfunction is characterized by reduced oxidative phosphorylation or increased generation of reactive oxygen species or both. In some embodiments, the disorder is type II diabetes. In some embodiments, the disorder is a neurodegenerative disease selected from Parkinson's or Huntington's disease. In some embodiments, the disorder is cardiovascular disease. In some embodiments, the disorder is cardiomyopathy.

In another aspect of the invention, methods are provided for determining compounds that are contraindicated in a subject, comprising (i) assaying for the effect of one or more compounds on (a) cellular dehydrogenase activity and (b) cell viability; and (ii) correlating the effect with contraindication of a compound, wherein a decrease in cellular dehydrogenase activity absent a decrease in cell viability indicates that the compound is contraindicated for said subjects.

In some embodiments, said subject is afflicted with a disorder characterized by mitochondrial dysfunction. In some embodiments, the method for determining compounds that are contraindicated in a subject further comprises assaying for the effect of one or more compounds on one or more of the following: OXPHOS gene expression; mitochondrial membrane potential; cellular ATP; reactive oxygen species (ROS), and cytochrome c protein, wherein an increase in OXPHOS gene expression, an increase in mitochondrial membrane potential; an increase in cellular ATP; an increase in ROS, and an increase in cytochrome c protein is indicative of a compound that enhances mitochondrial function. In some embodiments, mitochondrial function is assayed by measuring reactive oxygen species (ROS).

In some embodiments, an increase in OXPHOS gene expression and a decrease in ROS is indicative of a compound that enhances mitochondrial function. In some embodiments, cell viability is measured using calcein dye. In some embodiments, OXPHOS gene expression is measured using a gene expression-based high-throughput screening (GE-HTS) assay. In some embodiments, OXPHOS gene expression comprises the expression of the following genes: (a) Mt-Atp6 (Entrez GeneID numbers 17705 or 4508), (b) Mt-Atp8 (Entrez GeneID numbers 17706 or 4509), (c) Mt-Co1 (Entrez GeneID numbers 17708 or 4512), (d) Mt-Co2 (Entrez GeneID numbers 17709 or 4513), (e) Mt-Co3 (Entrez GeneID numbers 17710 or 4514), (f) Mt-Cytb (Entrez GeneID number 17711 or 4519), (g) Mt-Nd1 (Entrez GeneID numbers 17716 or 4535), (h) Mt-Nd2 (Entrez GeneID numbers 17717 or 4536), (i) Mt-Nd3 (Entrez GeneID numbers 17718 or 4537), (j) Mt-Nd4 (Entrez GeneID numbers 17719 or 4538), (k) Mt-Nd41 (Entrez GeneID numbers 17720 or 4539), (l) Mt-Nd5 (Entrez GeneID numbers 17721 or 4540), (m) Mt-Nd6 (Entrez GeneID numbers 17722 or 4541), (n) Atp5a1 (Entrez GeneID numbers 11946 or 498), (o) Atp5c1 (Entrez GeneID numbers 11949 or 509), (p) Atp5o (Entrez GeneID numbers 28080 or 539), (q) Cox5b (Entrez GeneID numbers 12859 or 1329), (r) Cox7a2 (Entrez GeneID numbers 12866 or 1347), (s) Cyc1 (Entrez GeneID numbers 66445 or 1537), (t) Hspc051 (Entrez GeneID number 66152 or 29796), (u) Ndufa5 (Entrez GeneID numbers 68202 or 4698), (v) Ndufb5 (Entrez GeneID numbers 66046 or 4711), (w) Sdhd (Entrez GeneID numbers 66925 or 6392), (x) Uqcrb (Entrez GeneID numbers 67530 or 7381), and (y) Uqcrc1 (Entrez GeneID numbers 22273 or 7384)

In some embodiments, the assays are performed in a multi-well plate format. In some embodiments, the one or more compounds comprise a library of compounds.

In some embodiments, the mitochondrial dysfunction is characterized by reduced oxidative phosphorylation or increased generation of reactive oxygen species or both. In some embodiments, the disorder is type II diabetes. In some embodiments, the disorder is a neurodegenerative disease selected from Parkinson's or Huntington's disease. In some embodiments, the disorder is cardiovascular disease. In some embodiments, the disorder is cardiomyopathy.

In another aspect of the invention, methods are provided for determining two or more compounds that are contraindicated for joint administration to a subject comprising (i) assaying for the effect of two or more compounds on (a) cellular dehydrogenase activity and (b) cell viability; and (ii) correlating the effect with contraindication of joint administration, wherein two or more compounds that each decrease cellular dehydrogenase activity absent a decrease in cell viability indicates that the two or more compounds are contraindicated when jointly administered to a subject. In some embodiments, the subject is afflicted with a disorder characterized by mitochondrial dysfunction. In some embodiments, the methods of determining two or more compounds that are contraindicated for joint administration to a subject further comprises assaying for the effect of one or more compounds on one or more of the following: OXPHOS gene expression; mitochondrial membrane potential; cellular ATP; reactive oxygen species (ROS), and cytochrome c protein, wherein an increase in OXPHOS gene expression, an increase in mitochondrial membrane potential; an increase in cellular ATP; an increase in ROS, and an increase in cytochrome c protein is indicative of a compound that enhances mitochondrial function. In some embodiments, mitochondrial function is assayed by measuring reactive oxygen species (ROS).

In some embodiments, the assays are performed in a multi-well plate format. In some embodiments, the one or more compounds comprise a library of compounds. In some embodiments, the mitochondrial dysfunction is characterized by reduced oxidative phosphorylation or increased generation of reactive oxygen species or both. In some embodiments, the disorder is type II diabetes. In some embodiments, the disorder is a neurodegenerative disease selected from Parkinson's or Huntington's disease. In some embodiments, wherein the disorder is cardiovascular disease. In some embodiments, the disorder is cardiomyopathy.

In another aspect of the invention, a kit for determining OXPHOS gene expression is provided, comprising a set of primer pairs, each pair amplifying an OXPHOS gene selected from a group consisting of the following: (a) Mt-Atp6 (Entrez GeneID numbers 17705 or 4508), (b) Mt-Atp8 (Entrez GeneID numbers 17706 or 4509), (c) Mt-Co1 (Entrez GeneID numbers 17708 or 4512), (d) Mt-Co2 (Entrez GeneID numbers 17709 or 4513), (e) Mt-Co3 (Entrez GeneID numbers 17710 or 4514), (f) Mt-Cytb (Entrez GeneID number 17711 or 4519), (g) Mt-Nd1 (Entrez GeneID numbers 17716 or 4535), (h) Mt-Nd2 (Entrez GeneID numbers 17717 or 4536), (i) Mt-Nd3 (Entrez GeneID numbers 17718 or 4537), (o) Mt-Nd4 (Entrez GeneID numbers 17719 or 4538), (k) Mt-Nd41 (Entrez GeneID numbers 17720 or 4539), (l) Mt-Nd5 (Entrez GeneID numbers 17721 or 4540), (m) Mt-Nd6 (Entrez GeneID numbers 17722 or 4541), (n) Atp5a1 (Entrez GeneID numbers 11946 or 498), (o) Atp5c1 (Entrez GeneID numbers 11949 or 509), (p) Atp5o (Entrez GeneID numbers 28080 or 539), (q) Cox5b (Entrez GeneID numbers 12859 or 1329), (r) Cox7a2 (Entrez GeneID numbers 12866 or 1347), (s) Cyc1 (Entrez GeneID numbers 66445 or 1537), (t) Hspc051 (Entrez GeneID number 66152 or 29796), (u) Ndufa5 (Entrez GeneID numbers 68202 or 4698), (v) Ndufb5 (Entrez GeneID numbers 66046 or 4711), (w) Sdhd (Entrez GeneID numbers 66925 or 6392), (x) Uqcrb (Entrez GeneID numbers 67530 or 7381), and (y) Uqcrc1 (Entrez GeneID numbers 22273 or 7384).

In some embodiments, the first primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 1 and a second primer comprising the nucleotide sequence of SEQ ID NO: 2; the second primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 3 and a second primer comprising the nucleotide sequence of SEQ ID NO: 4; the third primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 5 and a second primer comprising the nucleotide sequence of SEQ ID NO: 6; the fourth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 7 and a second primer comprising the nucleotide sequence of SEQ ID NO: 8; the fifth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 9 and a second primer comprising the nucleotide sequence of SEQ ID NO: 10, the sixth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 11 and a second primer comprising the nucleotide sequence of SEQ ID NO: 12, the seventh primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 13 and a second primer comprising the nucleotide sequence of SEQ ID NO: 14, the eighth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 15 and a second primer comprising the nucleotide sequence of SEQ ID NO: 16, the ninth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 17 and a second primer comprising the nucleotide sequence of SEQ ID NO: 18, the tenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 19 and a second primer comprising the nucleotide sequence of SEQ ID NO: 20, the eleventh primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 21 and a second primer comprising the nucleotide sequence of SEQ ID NO: 22, the twelfth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 23 and a second primer comprising the nucleotide sequence of SEQ ID NO: 24, the thirteenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 25 and a second primer comprising the nucleotide sequence of SEQ ID NO: 26, the fourteenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 27 and a second primer comprising the nucleotide sequence of SEQ ID NO: 28, the fifteenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 29 and a second primer comprising the nucleotide sequence of SEQ ID NO: 30, the sixteenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 31 and a second primer comprising the nucleotide sequence of SEQ ID NO: 32, the seventeenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 33 and a second primer comprising the nucleotide sequence of SEQ ID NO: 34, the eighteenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 35 and a second primer comprising the nucleotide sequence of SEQ ID NO: 36, the nineteenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 37 and a second primer comprising the nucleotide sequence of SEQ ID NO: 38, the twentieth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 39 and a second primer comprising the nucleotide sequence of SEQ ID NO: 40, the twenty-first primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 41 and a second primer comprising the nucleotide sequence of SEQ ID NO: 42, the twenty-second primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 43 and a second primer comprising the nucleotide sequence of SEQ ID NO: 44, the twenty-third primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 45 and a second primer comprising the nucleotide sequence of SEQ ID NO: 46, the twenty-fourth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 47 and a second primer comprising the nucleotide sequence of SEQ ID NO: 48, the twenty-fifth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 49 and a second primer comprising the nucleotide sequence of SEQ ID NO: 50.

In some embodiments, the kit comprises at least one primer pair that amplifies a gene showing little or no upregulation by PGC-1a. In some embodiments, at least one primer pair amplifies a gene selected from (a) Actb (Entrez GeneID 11461), (b) Aamp (Entrez GeneID 227290), (c) Cenpb (Entrez GeneID 12616), (d) Eefla1 (Entrez GeneID 13627), (e) Jund (Entrez GeneID 16478), (f) Lsp1 (Entrez GeneID 16985), (g) Rps2 (Entrez GeneID 16898), and (h) Rps27a (Entrez GeneID 78294). In some embodiments, the first primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 51 and a second primer comprising the nucleotide sequence of SEQ ID NO: 52; the second primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 53 and a second primer comprising the nucleotide sequence of SEQ ID NO: 54; the third primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 55 and a second primer comprising the nucleotide sequence of SEQ ID NO: 56; the fourth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 57 and a second primer comprising the nucleotide sequence of SEQ ID NO: 58; the fifth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 59 and a second primer comprising the nucleotide sequence of SEQ ID NO: 60, the sixth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 61 and a second primer comprising the nucleotide sequence of SEQ ID NO: 62, the seventh primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 63 and a second primer comprising the nucleotide sequence of SEQ ID NO: 64, the eighth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 65 and a second primer 66.

In some embodiments, the kit further comprises at least one primer pair that amplifies a genes that is down-regulated by PGC-1α. In some embodiments, at least one primer pair amplifies a gene selected from (a) Cyb5r3 (Entrez Gene ID 109754), and (b) Fh11 (Entrez Gene ID 14199).

In some embodiments, the first primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 67 and a second primer comprising the nucleotide sequence of SEQ ID NO: 68; the second primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 69 and a second primer comprising the nucleotide sequence of SEQ ID NO: 70.

In some embodiments, the kit further comprises reagents for amplifying DNA, wherein the reagents include a DNA polymerase.

In other embodiments, the kit comprises a plurality of primer pairs wherein each primer pair comprises a first nucleic acid sequence and a second nucleic acid sequence, which first nucleic acid sequence hybridizes under stringent conditions to a first strand of a target sequence, and which second nucleic acid sequence hybridizes under stringent conditions to a second strand of a target sequence, wherein the target sequence is selected from a group consisting of the following: (a) Mt-Atp6, (b) Mt-Atp8, (c) Mt-Co1, (d) Mt-Co2, (e) Mt-Co3, (f) Mt-Cytb, (g) Mt-Nd1, (h) Mt-Nd2, (i) Mt-Nd3, (j) Mt-Nd4, (k) Mt-Nd41, (l) Mt-Nd5, (m) Mt-Nd61, (n) Atp5a1, (o) Atp5c1, (p) Atp5o, (q) Cox5b, (r) Cox7a2, (s) Cyc1, (t) Hspc051, (u) Ndufa5, (v) Ndufb5, (w) Sdhd, (x) Uqcrb, and (y) Uqcrc1.

In some embodiments, primers in the primer pair hybridize under stringent conditions to the 3′ ends of the strands of the target sequence.

In some embodiments, the target sequence may be the entire gene or any appropriate region thereof.

In some embodiments, the kit comprises a first nucleic acid and/or the second nucleic acid further comprises a tag sequence. In some embodiments, the tag sequence is covalently linked to the 5′ end of the first and/or the second nucleic acid.

In further embodiments, the kit comprises a tag sequence that does not hybridize to the target sequence.

In additional embodiments, the kit comprises tag sequences, wherein said tag sequences are selected from the following: (a) SEQ ID NO:71, (b) SEQ ID NO:72, (c) SEQ ID NO:73, (d) SEQ ID NO:74, (e) SEQ ID NO:75, (f) SEQ ID NO:76, (g) SEQ ID NO:77, (h) SEQ ID NO:78, (i) SEQ ID NO:79, (j) SEQ ID NO:80, (k) SEQ ID NO:81, (l) SEQ ID NO:82, (m) SEQ ID NO:83, (n) SEQ ID NO:84, (o) SEQ ID NO:85, (p) SEQ ID NO:86, (q) SEQ ID NO:87, (r) SEQ ID NO:88, (s) SEQ ID NO:89, (t) SEQ ID NO:90, (u) SEQ ID NO:91, (v) SEQ ID NO:92, (w) SEQ ID NO:93, (x) SEQ ID NO:94, (y) SEQ ID NO:95, (z) SEQ ID NO:96, (aa) SEQ ID NO:97, (bb) SEQ ID NO:98, (cc) SEQ ID NO:99, (dd) SEQ ID NO:100, (ee) SEQ ID NO:101, (ff) SEQ ID NO:102, (gg) SEQ ID NO:103, (hh) SEQ ID NO:104, (ii) SEQ ID NO:105.

In other embodiments, the kit comprises a plurality of primer pairs, wherein each nucleic acid in the primer pair comprises a nucleic acid sequence that hybridizes under stringent conditions to the target sequence, is covalently linked to a tag sequence and/or an additional nucleic acid sequence. In some embodiments, primers in said primer pair hybridize under stringent conditions to the 3′ ends of the strands of the target sequence. In some embodiments, the additional nucleic acid sequence is not represented in either the target sequence or the tag sequence. In additional embodiments, the additional nucleic acid sequence comprises the binding site for a universal primer such as T3 or T7.

In some embodiments, the tag sequences comprise any one of SEQ ID NOs 71-105, listed in Table 9. In some embodiments, the additional nucleic acid sequence comprises the binding site for a universal primer, such as, but not limited to, T3 or T7. In some embodiments, the universal primers comprise either one of SEQ ID NOs 106-107, listed in Table 9. The primer sequences set forth herein may be combined with any one of the tag sequences provided herein or known in the art. For example, SEQ ID 108 is a primer sequence comprising the tag of SEQ ID NO: 76 linked to the universal primer of SEQ ID NO: 106 and further linked to the target specific primer of SEQ ID NO: 1. Other exemplary combinations are listed in Table 10 (SEQ ID NO: 108-176), and represent a subset of possible combinations.

In one aspect of the invention, methods are provided for detecting levels of at least 2 OXPHOS genes, comprising: (1) providing one or more target sequences selected from the following: (a) Mt-Atp6, (b) Mt-Atp8, (c) Mt-Co1, (d) Mt-Co2, (e) Mt-Co3, (f) Mt-Cytb, (g) Mt-Nd1, (h) Mt-Nd2, (i) Mt-Nd3, (j) Mt-Nd4, (k) Mt-Nd41, (l) Mt-Nd5, (m) Mt-Nd61, (n) Atp5a1, (o) Atp5c1, (p) Atp5o, (q) Cox5b, (r) Cox7a2, (s) Cyc1, (t) Hspc051, (u) Ndufa5, (v) Ndufb5, (w) Sdhd, (x) Uqcrb, and (y) Uqcrc1, (2) providing the plurality of primers that hybridize under stringent conditions to a target sequence from step (1), (3) amplifying target sequences using primers, (4) amplifying the sequences of step (3) using 2 nucleic acid sequences that are complementary to at least 1 portion of the primers of step (2), wherein one nucleic acid sequence is linked to a binding moiety, and one nucleic acid sequence is phosphorylated, and (5) identifying the amplification products of step (4) by hybridization to a nucleic acid sequence that is complementary to a portion of the amplification product, wherein nucleic acid sequence is covalently linked to a detectable moiety.

In some embodiments, amplification products are quantified by binding a second detectable moiety to said binding moiety.

In other embodiments, the binding moiety is biotin and said second binding moiety is avidin or streptavidin.

In further embodiments, the detectable moiety is a microsphere.

In other embodiments, steps (1)-(4) of the method are performed in a microtiter plate.

One aspect of the invention provides methods of treating or preventing a disorder characterized by mitochondrial dysfunction in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound selected from mebendazole, cytochalasin E, deoxysappanone (deoxysappanone b 7,3′-dimethyl ether), nocodazole, paclitaxel podofilox, podophyllotoxin acetate or vinblastine, or a metabolite or analog thereof.

In some embodiments the mitochondrial dysfunction is characterized by reduced oxidative phosphorylation or increased generation of reactive oxygen species or both. In some embodiments, the disorder is diabetes, glucose intolerance, obesity, cardiac myopathy, premature aging, coronary atherosclerotic heart disease, diabetes mellitus, Alzheimer's Disease, Parkinson's Disease, Huntington's disease, dystonia, Leber's hereditary optic neuropathy (LHON), schizophrenia, myodegenerative disorders such as “mitochondrial encephalopathy, lactic acidosis, and stroke” (MELAS). and “myoclonic epilepsy ragged red fiber syndrome” (MERRF), NARP (Neuropathy; Ataxia; Retinitis Pigmentosa), MNGIE (Myopathy and external opthalmoplegia, neuropathy; gastro-intestinal encephalopathy), Keams-Sayre disease, Pearson's Syndrome, PEO (Progressive External Opthalmoplegia), congenital muscular dystrophy with mitochondrial structural abnormalities, Wolfram syndrome, Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy Deafness, Leigh's Syndrome, fatal infantile myopathy with severe mitochondrial DNA (mtDNA) depletion, benign “later-onset” myopathy with moderate reduction in mtDNA, dystonia, medium chain acyl-CoA dehydrogenase deficiency, arthritis, mitochondrial diabetes and deafness (MIDD), or mitochondrial DNA depletion syndrome.

In exemplary embodiments the disorder is obesity and/or diabetes. In some embodiments, the disorder is glucose intolerance. In some embodiments, the disorder is premature aging. In some embodiments, the subject has elevated gluconeogenesis. In some embodiments, the subject is afflicted with cancer.

In some embodiments, methods for treating diabetes comprise administering a therapeutic dosage of paclitaxel or a metabolite or analog thereof.

In some embodiments, the disorder is a neurodegenerative disorder. In some embodiments, the neurodegenerative disorder is characterized by neuronal cell death. In some embodiments, the neurodegenerative disorder is Parkinson disease, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Huntington's disease, Freidreich's ataxia, Familial British Dementia, Finnish-type Familial Amyloidoses, Frontotemporal Dementia, Senile Systemic Amyloidosis, Familial Amyloid Polyneuropathy, Transmissible Spongiform Encephalopathie, Gertsmann-Strausseler-Scheinker Syndrome, Fatal Familial Insomnia, Huntington's Chorea, Kuru, Familial amyloid polyneuropathy, Creutzfeldt Jakob, Scrapie, and Bovine Spongiform Encephalopathy.

In some embodiments, the disorder is an mtDNA-associated disease. In some embodiments, the mt-DNA associated disease is MERRF, MELAS, LHON, MILASA, MILS, PEO or KSS.

One aspect of the invention also provides for compositions and combinations of compositions useful in treating or preventing a disorder characterized by mitochondrial dysfunction in a subject. In one embodiment, the composition comprises one or more of mebendazole, cytochalasin E, deoxysappanone, nocodazole, paclitaxel podofilox, podophyllotoxin acetate or vinblastine, or a metabolite or analog thereof.

In some embodiments, mebendazole or a metabolite or analog thereof is administered or formulated in a composition. In some embodiments, the subject is not afflicted with a worm infection.

In some embodiments, cytochalasin E or a metabolite or analog thereof is administered or formulated in a composition. In some embodiments of the methods, deoxysappanone or a metabolite or analog thereof is administered or formulated in a composition. In some embodiments, nocodazole or a metabolite or analog thereof is administered or formulated in a composition. In some embodiments, paclitaxel or a metabolite or analog thereof is administered or formulated in a composition. In some embodiments, podofilox or a metabolite or analog thereof is administered or formulated in a composition. In some embodiments, podophyllotoxin acetate or a metabolite or analog thereof is administered or formulated in a composition. In some embodiments, vinblastine or a metabolite or analog thereof is administered or formulated in a composition.

In some embodiments, one or more agents selected from sulfonylureas, non-sulfonylurea secretagogues, insulin, insulin analogs, glucagon-like peptides, exendin-4 polypeptides, beta 3 adrenoceptor agonists, PPAR agonists, dipeptidyl peptidase IV inhibitors, biguanides, alpha-glucosidase inhibitors, immunomodulators, statins and statin-containing combinations, angiotensin converting enzyme inhibitors, adenosine A1 receptor agonists, adenosine A2 receptor agonists, aldosterone antagonists, alpha 1 adrenoceptor antagonists, alpha 2 adrenoceptor agonists, alpha 2 adrenoceptor agonists, angiotensin receptor antagonists, antioxidants, ATPase inhibitors, atrial peptide agonists, beta adrenoceptor antagonists, calcium channel agonists, calcium channel antagonists, diuretics, dopamine D1 receptor agonists, endopeptidase inhibitors, endothelin receptor antagonists, guanylate cyclase stimulants, phosphodiesterase V inhibitors, protein kinase inhibitors, Cdc2 kinase inhibitors, renin inhibitors, thromboxane synthase inhibitors, vasopeptidase inhibitors, vasopressin I antagonists, vasopressin 2 antagonists, angiogenesis inhibitors, advanced glycation end product inhibitors, bile acid binding agents, bile acid transport inhibitors, bone formation stimulants, apolipoprotein A1 agonists, DNA topoisomerase inhibitors, cholesterol absorption inhibitors, cholesterol antagonists, cholesteryl ester transfer protein antagonists, cytokine synthesis inhibitors, DNA polymerase inhibitors, dopamine D2 receptor agonists, endothelin receptor antagonists, growth hormone antagonists, insulin sensitizers, lipase inhibitors, lipid peroxidation inhibitors, lipoprotein A antagonists, microsomal transport protein inhibitors, microsomal triglyceride transfer protein inhibitors, nitric oxide synthase inhibitors, oxidizing agents, phospholipase A2 inhibitors, radical formation agonists, platelet aggregation antagonists, prostaglandin synthase stimulants, reverse cholesterol transport activators, rho kinase inhibitors, selective estrogen receptor modulators, squalene epoxidase inhibitors, squalene synthase inhibitors, thromboxane A2 antagonists, amylin agonists, cannabinoid receptor antagonists, cholecystokinin A agonists, corticotropin-releasing factor agonists, dopamine uptake inhibitors, G protein-coupled receptor modulators, glutamate antagonists, glucagon-like peptide-1 agonists, insulin sensitizers, lipase inhibitors, melanin-concentrating hormone receptor antagonists, nerve growth factor agonists, neuropeptide Y agonists, neuropeptide Y antagonists, SNRIs, protein tyrosine phosphatase inhibitors, serotonin 2C receptor agonists, bezafibrate, diflunisal, or cinnamic acid may also be administered or formulated in a composition.

In some embodiments, sulfonylurea is selected from the group consisting of acetohexamide, chlorpropamide, tolazamide, tolbutamide, glimepiride, glipizide, and glyburide. In some embodiments, non-sulfonylurea secretagogue is nateglinide or repaglinide. In some embodiments, insulin analog is selected from the group consisting of insulin lispro, insulin aspart, insulin glarginine, NPH, lente insulin, ultralente insulin, humulin, and novolin. In some embodiments, PPAR.gamma. agonist is selected from the group consisting of balaglitazone, troglitazone, pioglitazone, ciglitazone, englitazone, rosiglitazone, darglitazone, englitazone, netoglitazone, KRP-297, JTT-501, NC-2100, NIP-223, MCC-555, L-764486, CS-011, G1262570, GW347845, and FK614. In some embodiments, biguanide is metformin or metformin/glyburide. In some embodiments, alpha-glucosidase inhibitor is acarbose or miglitol. In some embodiments, immunomodulator is a corticosteroid, cyclophosphamide, or NsIDI. In some embodiments, angiotensin converting enzyme (ACE) inhibitor is selected from the group consisting of benazepril, captopril, cilazapril, enalapril, enalaprilat, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril. In some embodiments, angiotensin II receptor blocker is selected from the group consisting of candesartan, eprosartan, irbesarten, losartin, telmisartan, and valsartan. In some embodiments, antioxidant is selected from the group consisting of nicotinamide, vitamin E, probucol, MDL29311, and U78518F. In some embodiments, exendin 4 is AC2993. In some embodiments, glucagon-like peptide is GLP-1.

DETAILED DESCRIPTION OF THE INVENTION
I. Overview

One aspect of the invention provides novel methods of treating disorders characterized by mitochondrial dysfunction. In one aspect, the disorders are characterized by reduced oxidative phosphorylation and/or increased production of reactive oxygen species (ROS). The disorders characterized by mitochondrial dysfunction may be treated by the administration of compounds disclosed herein. In some embodiments, the subject may be treated by the administration of mebendazole, cytochalasin E, deoxysappanone, nocodazole, paclitaxel podofilox, podophyllotoxin acetate or vinblastine, or a metabolite or analog thereof. In some embodiments, the disorders may be treated by the administration of a derivative of deoxysappone. These compounds may be administered in combination with other therapeutic agents. In addition, their pharmaceutically acceptable forms, including isomers such as diastereomers and enantiomers, salts, esters, solvates, and polymorphs thereof, as well as racemic mixtures and pure isomers of the compounds described herein, may be used in the treatments. In some embodiments, the methods of the invention comprise the administration of microtubule modulators which inhibit or promote tubulin polymerization.

One aspect of the invention provides methods of treating congenital mitochondrial diseases. These diseases are those related to hereditary mutations, deletions, or other defects in mitochondrial DNA or in nuclear genes regulating mitochondrial DNA integrity, or in nuclear genes encoding proteins that are critical for mitochondrial respiratory chain function. One aspect of the invention provides methods of treating acquired mitochondrial defects.

These comprise primarily 1) damage to mitochondrial DNA due to oxidative processes or aging; 2) mitochondrial dysfunction due to excessive intracellular and intramitochondrial calcium accumulation; 3) inhibition of respiratory chain complexes with endogenous or exogenous respiratory chain inhibitors; 4) acute or chronic oxygen deficiency; and 5) impaired nuclear-mitochondrial interactions, e.g. impaired shuttling of mitochondria in long axons due to microtubule defects.

In some embodiments, the mitochondrial disorders been treated by the compounds disclosed herein are characterized by excessive calcium accumulation. A fundamental mechanism of cell injury, especially in excitable tissues, involves excessive calcium entry into cells, as a result of either leakage through the plasma membrane or defects in intracellular calcium handling mechanisms. Mitochondria are major sites of calcium sequestration, and preferentially utilize energy from the respiratory chain for taking up calcium rather than for ATP synthesis, which results in a downward spiral of mitochondrial failure, since calcium uptake into mitochondria results in diminished capabilities for energy transduction.

In some embodiments, the mitochondrial disorders treatable by the compounds disclosed herein are characterized by excitotoxicity. Excessive stimulation of neurons with excitatory amino acids is a common mechanism of cell death or injury in the central nervous system. Activation of glutamate receptors, especially of the subtype designated NMDA receptors, results in mitochondrial dysfunction, in part through elevation of intracellular calcium during excitotoxic stimulation. Conversely, deficits in mitochondrial respiration and oxidative phosphorylation sensitize cells to excitotoxic stimuli, resulting in cell death or injury during exposure to levels of excitotoxic neurotransmitters or toxins that would be innocuous to normal cells.

In some embodiments, the mitochondrial disorders treatable by the compounds disclosed herein are characterized by nitric oxide exposure. Nitric oxide (1 micromolar) inhibits cytochrome oxidase (Complex IV) and thereby inhibits mitochondrial respiration. Moreover, prolonged exposure to NO irreversibly reduces Complex I activity. Physiological or pathophysiological concentrations of NO thereby inhibit pyrimidine biosynthesis. Nitric oxide is implicated in a variety of neurodegenerative disorders and is involved in mediation of excitotoxic and post-hypoxic damage to neurons.

In some embodiments, the mitochondrial disorders treatable by the compounds disclosed herein are characterized by hypoxia. Oxygen is the terminal electron acceptor in the respiratory chain. Oxygen deficiency impairs electron transport chain activity, resulting in diminished pyrimidine synthesis as well as diminished ATP synthesis via oxidative phosphorylation. Human cells proliferate and retain viability under virtually anaerobic conditions if provided with uridine and pyruvate (or a similarly effective agent for oxidizing NADH to optimize glycolytic ATP production).

In some embodiments, the mitochondrial disorders treatable by the compounds disclosed herein are characterized by nuclear-mitochondrial interactions. Transcription of mitochondrial DNA encoding respiratory chain components requires nuclear factors. In neuronal axons, mitochondria must shuttle back and forth to the nucleus in order to maintain respiratory chain activity. If axonal transport is impaired by hypoxia or by drugs like taxol that affect microtubule stability, mitochondria distant from the nucleus undergo loss of cytochrome oxidase activity.

The compounds and compositions of the invention are useful for treatment of a very broad spectrum of signs and symptoms in mitochondrial diseases with different underlying molecular pathologies, including those characterized by reduced oxidative phosphorylation and by generation of ROS. The broad applicability of the methods of the invention are unexpected. The set of compounds disclosed differ from other therapies of mitochondrial disease that have been attempted. For example, Coenzyme Q, B vitamins, carnitine, and lipoic acid, generally address very specific reactions and cofactors involved in mitochondrial function and which are therefore useful only in isolated cases. However, such metabolic interventions with antioxidants and cofactors of respiratory chain complexes are compatible with concurrent treatment with compounds and compositions of the invention and, in fact, are used to their best advantage in combination with compounds and compositions of the invention.

Treatment includes the application or administration of a therapeutic agent to a patient or application or administration of a therapeutic agent to an isolated tissue or cell line from a patient whom has a disease, a symptom of disease, or a predisposition toward a disease, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve or affect the disease, the symptoms of disease or the predisposition toward disease. The present invention also provides methods for screening compounds that enhance mitochondrial function, that are useful for treating disorders characterized by mitochondrial dysfunction, or that are contraindicated for patient use. As such, these methods can be used to prioritize large numbers of new compounds for further drug development. The adaptability of these in vitro methods for high-throughput analysis makes them an economical and cost-effective addition to a drug discovery program.

II. Definitions

For convenience, certain terms employed in the specification, examples, and appended claims, are collected here. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

The term “including” is used herein to mean, and is used interchangeably with, the phrase “including but not limited” to.

The term “or” is used herein to mean, and is used interchangeably with, the term “and/or,” unless context clearly indicates otherwise.

The term “such as” is used herein to mean, and is used interchangeably, with the phrase “such as but not limited to”.

The term “nucleic acid” refers to polynucleotides such as deoxyribonucleic acid (DNA), and, where appropriate, ribonucleic acid (RNA). The term should also be understood to include, as equivalents, analogs of either RNA or DNA made from nucleotide analogs, and, as applicable to the embodiment being described, single (sense or antisense) and double-stranded polynucleotides.

The term “preventing” is art-recognized and when used in relation to a condition, such as a local recurrence (e.g., pain), a disease such as cancer, a syndrome complex such as heart failure or any other medical condition, is well understood in the art and includes administering prior to onset of the condition a composition that reduces the frequency of, reduces the severity of, or delays the onset of symptoms of a medical condition in a subject relative to a subject which does not receive the composition. Thus, prevention of cancer includes, for example, reducing the number of detectable cancerous growths in a population of patients receiving a prophylactic treatment relative to an untreated control population, and/or delaying the appearance of detectable cancerous growths in a treated population versus an untreated control population, e.g., by a statistically and/or clinically significant amount. Prevention of an infection includes, for example, reducing the number of diagnoses of the infection in a treated population versus an untreated control population, and/or delaying the onset of symptoms of the infection in a treated population versus an untreated control population.

The term “effective amount” as used herein is defined as an amount effective, at dosages and for periods of time necessary to achieve the desired result. The effective amount of a compound of the invention may vary according to factors such as the disease state, age, sex, and weight of the animal. Dosage regimens may be adjusted to provide the optimum therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation.

A “subject” as used herein refers to any vertebrate animal, preferably a primate or mammal, and more preferably a human. Examples of subjects include humans, non-human primates, rodents, guinea pigs, rabbits, sheep, pigs, goats, cows, horses, dogs, cats, birds, and fish.

By “treating, reducing, or preventing a metabolic disorder” it is meant ameliorating such a condition before or after it has occurred. As compared with an equivalent untreated control, such reduction or degree of prevention is at least 5%, 10%, 20%, 40%, 50%, 60%, 80%, 90%, 95%, or 100% as measured by any standard technique.

By “a metabolic disorder” is meant any pathological condition resulting from an alteration in a patient's metabolism. Such disorders include those resulting from an alteration in glucose homeostasis resulting, for example, in hyperglycemia. According to this invention, an alteration in glucose levels is typically an increase in glucose levels by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or even 100% relative to such levels in a healthy individual. Metabolic disorders include obesity and diabetes (e.g., diabetes type I, diabetes type II, MODY, and gestational diabetes).

An “indicator of mitochondrial function” is any parameter that is indicative of mitochondrial function that can be measured by one skilled in the art. In certain embodiments, the indicator of mitochondrial function is a mitochondrial electron transport chain enzyme, a Krebs cycle enzyme, a mitochondrial matrix component, a mitochondrial membrane component or an ATP biosynthesis factor. In other embodiments, the indicator of mitochondrial function is mitochondrial number per cell or mitochondrial mass per cell. In other embodiments, the indicator of mitochondrial function is an ATP biosynthesis factor. In other embodiments, the indicator of mitochondrial function is the amount of ATP per mitochondrion, the amount of ATP per unit mitochondrial mass, the amount of ATP per unit protein or the amount of ATP per unit mitochondrial protein. In other embodiments, the indicator of mitochondrial function comprises free radical production. In other embodiments, the indicator of mitochondrial function comprises a cellular response to elevated intracellular calcium. In other embodiments, the indicator of mitochondrial function is the activity of a mitochondrial enzyme such as, by way of non-limiting example, citrate synthase, hexokinase II, cytochrome c oxidase, phosphofructokinase, glyceraldehyde phosphate dehydrogenase, glycogen phosphorylase, creatine kinase, NADH dehydrogenase, glycerol 3-phosphate dehydrogenase, triose phosphate dehydrogenase or malate dehydrogenase. In other embodiments, the indicator of mitochondrial function is the relative or absolute amount of mitochondrial DNA per cell in the patient.

“Improving, increasing, or enhancing mitochondrial function” or “altering mitochondrial function” may refer to (a) substantially (e.g., in a statistically significant manner, and preferably in a manner that promotes a statistically significant improvement of a clinical parameter such as prognosis, clinical score or outcome) restoring to a normal level at least one indicator of glucose responsiveness in cells having reduced glucose responsiveness and reduced mitochondrial mass and/or impaired mitochondrial function; or (b) substantially (e.g., in a statistically significant manner, and preferably in a manner that promotes a statistically significant improvement of a clinical parameter such as prognosis, clinical score or outcome) restoring to a normal level, or increasing to a level above and beyond normal levels, at least one indicator of mitochondrial function in cells having impaired mitochondrial function, or in cells having normal mitochondrial function, respectively. Improved or altered mitochondrial function may result from changes in extramitochondrial structures or events, as well as from mitochondrial structures or events, in direct interactions between mitochondrial and extramitochondrial genes and/or their gene products, or in structural or functional changes that occur as the result of interactions between intermediates that may be formed as the result of such interactions, including metabolites, catabolites, substrates, precursors, cofactors and the like.

“Impaired mitochondrial function” may include a full or partial decrease, inhibition, diminution, loss or other impairment in the level and/or rate of any respiratory, metabolic or other biochemical or biophysical activity in some or all cells of a biological source. As non-limiting examples, markedly impaired electron transport chain (ETC) activity may be related to impaired mitochondrial function, as may be generation of increased reactive oxygen species (ROS) or defective oxidative phosphorylation. As further examples, altered mitochondrial membrane potential, induction of apoptotic pathways and formation of atypical chemical and biochemical crosslinked species within a cell, whether by enzymatic or non-enzymatic mechanisms, may all be regarded as indicative of mitochondrial function. These and other non-limiting examples of impaired mitochondrial function are described in greater detail below.

A mitochondrial enzyme that may be an indicator of mitochondrial function

III. Methods of Treatment

One aspect of the invention provides methods of treating, aiding in the treatment, preventing, or reducing the symptoms of a disorder characterized by mitochondrial dysfunction. Mitochondrial dysfunction may be diagnosed by a clinician. Symptoms of mitochondrial dysfunction may include idiopathic neuromuscular and/or multisystem disease or biochemical signs of energy depletion. Mitochondrial disorders are most commonly displayed as neuromuscular disorders, including developmental delay, seizure disorders, hypotonia, skeletal muscle weakness and cardiomyopathy. One method of identifying subjects having mitochondrial dysfunction is disclosed in U.S. Pat. No. 6,759,196. “Mitochondrial dysfunction” also refers to disorders to which deficits in mitochondrial respiratory chain activity contribute in the development of pathophysiology of such disorders in a mammal. This category includes 1) congenital genetic deficiencies in activity of one or more components of the mitochondrial respiratory chain; 2) acquired deficiencies in the activity of one or more components of the mitochondrial respiratory chain, wherein such deficiencies are caused by, inter alia, a) oxidative damage during aging; b) elevated intracellular calcium; c) exposure of affected cells to nitric oxide; d) hypoxia or ischemia; or e) microtubule-associated deficits in axonal transport of mitochondria.

One aspect of the invention provides methods of treating congenital mitochondrial cytopathies, the method comprising administering to the subject a therapeutically effective amount of one or more compounds described herein. In one embodiment, the method comprises administering to the subject a microtubule modulator. In one embodiment, the microtubule modulator is podofilox, vinblastine sulfate, mebendazole, pocodazole, podophyllotoxin, paclitaxela, albendazole, picropodophyllotoxin, griseofulvin, paclitaxel, coichicine, mebendazole, trifluralin, or griseofulvin

Congenital mitochondrial cytopathies include those characterized by mitochondrial DNA defects. A number of clinical syndromes have been linked to mutations or deletions in mitochondrial DNA. Mitochondrial DNA is inherited maternally with virtually all of the mitochondria in the body derived from those provided by the oocyte. If there is a mixture of defective and normal mitochondria in an oocyte, the distribution and segregation of mitochondria is a stochastic process. Thus, mitochondrial diseases are often multisystem disorders, and a particular point mutation in mitochondrial DNA, for example, can result in dissimilar sets of signs and symptoms in different patients. Conversely, mutations in two different genes in mitochondrial DNA can result in similar symptom complexes. Nonetheless, some consistent symptom patterns have emerged in conjunction with identified mitochondrial DNA defects, and these comprise the classic “mitochondrial diseases.” An important aspect of the subject invention is the recognition that the concept of mitochondrial disease and its treatment with compounds and compositions of the invention extends to many other disease conditions which are also disclosed herein.

Some of the major mitochondrial diseases associated with mutations or deletions of mitochondrial DNA include: MELAS (Mitochondrial Encephalomyopathy Lactic Acidemia and Stroke-like episodes), MERRF (Myoclonic Epilepsy with “Ragged Red” (muscle) Fibers), NARP (Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa), LHON (Leber's Hereditary Optic Neuropathy), Leigh's Syndrome (Subacute Necrotizing Encephalomyopathy), PEO (Progressive External Opthalmoplegia), and Kearns-Sayres Syndrome (PEO, pigmentary retinopathy, ataxia, and heart-block). Other common symptoms of mitochondrial diseases that may be present alone or in conjunction with these syndromes include cardiomyopathy, muscle weakness and atrophy, developmental delays (involving motor, language, cognitive or executive function), ataxia, epilepsy, renal tubular acidosis, peripheral neuropathy, optic neuropathy, autonomic neuropathy, neurogenic bowel dysfunction, sensorineural deafness, neurogenic bladder dysfunction, dilating cardiomyopathy, migraine, hepatic failure, lactic acidemia, and diabetes mellitus.

In addition to the gene products and tRNA encoded by mitochondrial DNA, many proteins involved in or affecting mitochondrial respiration and oxidative phosphorylation are encoded by nuclear DNA. In fact, approximately 3000 proteins, or 20% of all proteins encoded by the nuclear genome, are physically incorporated into, or associated with, mitochondria and mitochondrial functions, although only about 100 are directly involved as structural components of the respiratory chain. Therefore, mitochondrial diseases involve not only gene products of mitochondrial DNA, but also nuclear encoded proteins affecting respiratory chain function.

Metabolic stressors, such as infection, can unmask mitochondrial defects that do not necessarily yield symptoms under normal conditions. Neuromuscular or neurological setbacks during infection are a hallmark of mitochondrial disease. Conversely, mitochondrial respiratory chain dysfunction can render cells vulnerable to stressors that would otherwise be innocuous.

One aspect of the invention provides methods of treating neuromuscular degenerative disorders, the method comprising administering to the subject a therapeutically effective amount of a compound described herein. In some embodiments, the compound is selected from mebendazole, cytochalasin E, deoxysappanone, nocodazole, paclitaxel podofilox, podophyllotoxin acetate or vinblastine, or a metabolite or analog thereof. In one embodiment, the method comprises administering to the subject a microtubule modulator.

In one embodiment, the neuromuscular degenerative disorder is Friedreich's Ataxia (FA). A gene defect underlying Friedreich's Ataxia (FA), the most common hereditary ataxia, was recently identified and is designated “frataxin”. In FA, after a period of normal development, deficits in coordination develop which progress to paralysis and death, typically between the ages of 30 and 40. The tissues affected most severely are the spinal cord, peripheral nerves, myocardium, and pancreas. Patients typically lose motor control and are confined to wheelchairs and are commonly afflicted with heart failure and diabetes. The genetic basis for FA involves GAA trinucleotide repeats in an intron region of the gene encoding frataxin. The presence of these repeats results in reduced transcription and expression of the gene. Frataxin is involved in regulation of mitochondrial iron content. When cellular frataxin content is subnormal, excess iron accumulates in mitochondria, promoting oxidative damage and consequent mitochondrial degeneration and dysfunction.

Compounds and compositions of the invention are useful for treating patients with disorders related to deficiencies or defects in frataxin, including Friedreich's Ataxia, myocardial dysfunction, diabetes mellitus and complications of diabetes like peripheral neuropathy. Conversely, diagnostic tests for presumed frataxin deficiencies involving PCR tests for GAA intron repeats are useful for identifying patients who will benefit from treatment with compounds and compositions of the invention.

In one embodiment, the neuromuscular degenerative disorder is muscular dystrophy (MD). MD refers to a family of diseases involving deterioration of neuromuscular structure and function, often resulting in atrophy of skeletal muscle and myocardial dysfunction. In the case of Duchenne muscular dystrophy, mutations or deficits in a specific protein, dystrophin, are implicated in its etiology. Mice with their dystrophin genes inactivated display some characteristics of muscular dystrophy, and have an approximately 50% deficit in mitochondrial respiratory chain activity. A final common pathway for neuromuscular degeneration in most cases is calcium-mediated impairment of mitochondrial function. Compounds and compositions of the invention are useful for reducing the rate of decline in muscular functional capacities and for improving muscular functional status in patients with muscular dystrophy.

In one embodiment, the neuromuscular degenerative disorder is multiple sclerosis (MS). MS (MS) is a neuromuscular disease characterized by focal inflammatory and autoimmune degeneration of cerebral white matter. Periodic exacerbations or attacks are significantly correlated with upper respiratory tract and other infections, both bacterial and viral, indicating that mitochondrial dysfunction plays a role in MS. Nitric oxide Depression of neuronal mitochondrial respiratory chain activity caused by Nitric Oxide (produced by astrocytes) is implicated as a molecular mechanism contributing to MS. Compounds and compositions of the invention are useful for treatment of patients with multiple sclerosis, both prophylactically and during episodes of disease exacerbation.

One aspect of the invention provides methods of treating seizure disorders, the method comprising administering to the subject a therapeutically effective amount of a compound described herein. In some embodiments, the compound is selected from mebendazole, cytochalasin E, deoxysappanone, nocodazole, paclitaxel podofilox, podophyllotoxin acetate or vinblastine, or a metabolite or analog thereof. In one embodiment, the method comprises administering to the subject a microtubule modulator. In one embodiment, the seizure disorder is epilepsy. The term “epilepsy” refers to any neurological condition that makes people susceptible to seizures. A seizure is a change in sensation, awareness, or behavior brought about by a brief electrical disturbance in the brain. Seizures vary from a momentary disruption of the senses, to short periods of unconsciousness or staring spells, to convulsions. Some people have just one type of seizure. Others have more than one type. Although they look different, all seizures are caused by the same thing: a sudden change in how the cells of the brain send electrical signals to each other. Epilepsy is often present in patients with mitochondrial cytopathies, involving a range of seizure severity and frequency, e.g. absence, tonic, atonic, myoclonic, and status epilepticus, occurring in isolated episodes or many times daily. In patients with seizures secondary to mitochondrial dysfunction, compounds and methods of the invention are useful for reducing frequency and severity of seizure activity.

The compounds of the invention may also be used to treat and prevent migraines. Metabolic studies on patients with recurrent migraine headaches indicate that deficits in mitochondrial activity are commonly associated with this disorder, manifesting as impaired oxidative phosphorylation and excess lactate production. Such deficits are not necessarily due to genetic defects in mitochondrial DNA. Migraine sufferers are hypersensitive to nitric oxide, an endogenous inhibitor of Cytochrome c Oxidase. In addition, patients with mitochondrial cytopathies, e.g. MELAS, often have recurrent migraines. In patients with recurrent migraine headaches, compounds, compositions, and methods of the invention are useful for prevention and treatment, especially in the case of headaches refractory to ergot compounds or serotonin receptor antagonists.

One aspect of the invention provides methods of treating mitochondrial-associated developmental delays, the method comprising administering to the subject a therapeutically effective amount of a compound described herein. In some embodiments, the compound is selected from mebendazole, cytochalasin E, deoxysappanone, nocodazole, paclitaxel podofilox, podophyllotoxin acetate or vinblastine, or a metabolite or analog thereof. In one embodiment, the method comprises administering to the subject a microtubule modulator.

Delays in neurological or neuropsychological development are often found in children with mitochondrial diseases. Development and remodeling of neural connections requires intensive biosynthetic activity, particularly involving synthesis of neuronal membranes and myelin, both of which require pyrimidine nucleotides as cofactors. Uridine nucleotides are involved in activation and transfer of sugars to glycolipids and glycoproteins. Cytidine nucleotides are derived from uridine nucleotides, and are crucial for synthesis of major membrane phospholipid constituents like phosphatidylcholine, which receives its choline moiety from cytidine diphosphocholine. In the case of mitochondrial dysfunction (due to either mitochondrial DNA defects or any of the acquired or conditional deficits like exicitoxic or nitric oxide-mediated mitochondrial dysfunction described above) or other conditions resulting in impaired pyrimidine synthesis, cell proliferation and axonal extension is impaired at crucial stages in development of neuronal interconnections and circuits, resulting in delayed or arrested development of neuropsychological functions like language, motor, social, executive function, and cognitive skills. In autism for example, magnetic resonance spectroscopy measurements of cerebral phosphate compounds indicates that there is global undersynthesis of membranes and membrane precursors indicated by reduced levels of uridine diphospho-sugars, and cytidine nucleotide derivatives involved in membrane synthesis (Minshew et al., Biological Psychiatry 33:762-773, 1993).

Disorders characterized by developmental delay include Rett's Syndrome, pervasive developmental delay (or PDD-NOS: “pervasive developmental delay—not otherwise specified” to distinguish it from specific subcategories like autism), autism, Asperger's Syndrome, and Attention Deficit/Hyperactivity Disorder (ADHD), which is becoming recognized as a delay or lag in development of neural circuitry underlying executive functions.

The compounds and compositions of the invention are useful for treating patients with neurodevelopmental delays involving motor, language, executive function, and cognitive skills. Current treatments for such conditions, e.g. ADHD, involve amphetamine-like stimulants that enhance neurotransmission in some affected underdeveloped circuits, but such agents, which may improve control of disruptive behaviors, do not improve cognitive function, as they do not address underlying deficits in the structure and interconnectedness of the implicated neural circuits. Compounds and compositions of the invention are also useful in the case of other delays or arrests of neurological and neuropsychological development in the nervous system and somatic development in non-neural tissues like muscle and endocrine glands.

One aspect of the invention provides methods of treating neurodegenerative disorders, the method comprising administering to the subject a therapeutically effective amount of a compound described herein. In some embodiments, the compound is selected from mebendazole, cytochalasin E, deoxysappanone, nocodazole, paclitaxel podofilox, podophyllotoxin acetate or vinblastine, or a metabolite or analog thereof. In one embodiment, the method comprises administering to the subject a microtubule modulator.

The two most significant severe neurodegenerative diseases associated with aging, Alzheimer's Disease (AD) and Parkinson's Disease (PD), both involve mitochondrial dysfunction in their pathogenesis. Complex I deficiencies in particular are frequently found not only in the nigrostriatal neurons that degenerate in Parkinson's disease, but also in peripheral tissues and cells like muscle and platelets of Parkinson's Disease patients.

In Alzheimer's Disease, mitochondrial respiratory chain activity is often depressed, especially Complex IV (Cytochrome c Oxidase). Moreover, mitochondrial respiratory function altogether is depressed as a consequence of aging, further amplifying the deleterious consequences of additional molecular lesions affecting respiratory chain function.

Other factors in addition to primary mitochondrial dysfunction underlie neurodegeneration in AD, PD, and related disorders. Excitotoxic stimulation and nitric oxide are implicated in both diseases, factors which both exacerbate mitochondrial respiratory chain deficits and whose deleterious actions are exaggerated on a background of respiratory chain dysfunction. Compounds and compositions of the invention are useful for attenuating progression of age-related neurodegenerative disease including AD and PD.

Huntington's Disease also involves mitochondrial dysfunction in affected brain regions, with cooperative interactions of excitotoxic stimulation and mitochondrial dysfunction contributing to neuronal degeneration.

In one embodiment, the neurodegenerative disease is Amyotrophic Lateral Sclerosis (ALS; Lou Gehrig's Disease) characterized by progressive degeneration of motor neurons, skeletal muscle atrophy, and inevitably leading to paralysis and death. ALS is caused by a mutation or deficiency in Copper-Zinc Superoxide Dismutase (SOD1), an antioxidant enzyme. Mitochondria both produce and are primary targets for reactive oxygen species. Inefficient transfer of electrons to oxygen in mitochondria is the most significant physiological source of free radicals in mammalian systems. Deficiencies in antioxidants or antioxidant enzymes can result in or exacerbate mitochondrial degeneration. Mice transgenic for mutated SOD1 develop symptoms and pathology similar to those in human ALS. The development of the disease in these animals has been shown to involve oxidative destruction of mitochondria followed by functional decline of motor neurons and onset of clinical symptoms (Kong and Xu, J. Neurosci. 18:3241-3250, 1998). Skeletal muscle from ALS patients has low mitochondrial Complex I activity (Wiedemann et al., J. Neurol. Sci 156:65-72, 1998). Compounds, compositions, and methods of the invention are useful for treatment of ALS, for reversing or slowing the progression of clinical symptoms.

One aspect of the invention provides methods of protecting against ischemia and hypoxia, the method comprising administering to the subject a therapeutically effective amount of a compound described herein. In some embodiments, the compound is selected from mebendazole, cytochalasin E, deoxysappanone, nocodazole, paclitaxel podofilox, podophyllotoxin acetate or vinblastine, or a metabolite or analog thereof. In one embodiment, the method comprises administering to the subject a microtubule modulator.

Oxygen deficiency results in both direct inhibition of mitochondrial respiratory chain activity by depriving cells of a terminal electron acceptor for Cytochrome c reoxidation at Complex IV, and indirectly, especially in the nervous system, via secondary post-anoxic excitotoxicity and nitric oxide formation. In conditions like cerebral anoxia, angina or sickle cell anemia crises, tissues are relatively hypoxic. In such cases, compounds of the invention provide protection of affected tissues from deleterious effects of hypoxia, attenuate secondary delayed cell death, and accelerate recovery from hypoxic tissue stress and injury.

Another condition where the compounds described here may be useful to protect against ischemia is renal tubular acidosis. Acidosis due to renal dysfunction is often observed in patients with mitochondrial disease, whether the underlying respiratory chain dysfunction is congenital or induced by ischemia or cytotoxic agents like cisplatin. Renal tubular acidosis often requires administration of exogenous sodium bicarbonate to maintain blood and tissue pH.

One aspect of the invention provides methods of treating diabetes, including Type II diabetes, the method comprising administering to the subject a therapeutically effective amount of a compound described herein. In some embodiments, the compound is selected from mebendazole, cytochalasin E, deoxysappanone, nocodazole, paclitaxel podofilox, podophyllotoxin acetate or vinblastine, or a metabolite or analog thereof. In one embodiment, the method comprises administering to the subject a microtubule modulator. Diabetes mellitus is a high prevalence illness characterized by high blood glucose levels. The chronic hyperglycemia (high glucose level) of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels. The vast majority of cases of diabetes fall into two broad etiopathogenetic categories. The first category, type I or insulin-dependent diabetes mellitus (IDDM), results from an absolute deficiency of insulin due to autoimmunological destruction of the insulin-producing pancreatic β-cells. Another category, type 2 or non-insulin-dependent diabetes mellitus (NIDDM), which accounts for about 90% of all diabetes cases, is caused by a combination of resistance of insulin action and an inadequate compensatory insulin secretory response.

In one embodiment, the compound is administered in conjunction with other anti-diabetic treatments. Commonly used oral therapeutics for type 2 diabetes include thiazolidinediones (TZDs), sulfonylureas, metformin, and more recently, dipeptidyl peptidase IV (DPP-IV) inhibitors. Thiazolidinediones enhance insulin sensitivity by activating PPARγ receptors in adipose tissue and altering adipose metabolism and distribution (Spiegelman, 1998). Sulfonylureas promote insulin secretion by closing pancreatic cell potassium channels. Metformin decreases hepatocyte glucose production via an as yet unidentified mechanism of action. DPP-IV inhibitors are a new class of antidiabetic agent that prevents DPP-IV from degrading glucagon-like peptide-1 (GLP-1), a hormone that stimulates insulin secretion and reduces glucagon secretion from pancreas.

In one embodiment, administration of the compounds of the invention are useful for reducing glucose levels in a subject. By “reducing glucose levels” is meant reducing the level of glucose by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 100% relative to an untreated control. Desirably, glucose levels are reduced to normoglycemic levels, i.e., between 150 to 60 mg/dL, between 140 to 70 mg/dL, between 130 to 70 mg/dL, between 125 to 80 mg/dL, and preferably between 120 to 80 mg/dL. Such reduction in glucose levels may be obtained by increasing any one of the biological activities associated with the clearance of glucose from the blood. Accordingly, an agent having the ability to reduce glucose levels may increase insulin production, secretion, or action. Insulin action may be increased, for example, by increasing glucose uptake by peripheral tissues and/or by reducing hepatic glucose production.

Diagnosis of metabolic disorders, such as diabetes and glucose intolerance, may be performed using any standard method known in the art. Methods for diagnosing diabetes are described, for example, in U.S. Pat. No. 6,537,806, hereby incorporated by reference. Diabetes may be diagnosed and monitored using, for example, urine tests (urinalysis) that measure glucose and ketone levels (products of the breakdown of fat); tests that measure the levels of glucose in blood; glucose tolerance tests; and assays that detect molecular markers characteristic of a metabolic disorder in a biological sample (e.g., blood, serum, or urine) collected from the mammal (e.g., measurements of Hemoglobin Alc (HbAlc) levels in the case of diabetes).

Patients may be diagnosed as being at risk or as having diabetes if a random plasma glucose test (taken at any time of the day) indicates a value of 200 mg/dL or more, if a fasting plasma glucose test indicates a value of 126 mg/dL or more (after 8 hours), or if an oral glucose tolerance test (OGTT) indicates a plasma glucose value of 200 mg/dL or more in a blood sample taken two hours after a person has consumed a drink containing 75 grams of glucose dissolved in water. The OGTT measures plasma glucose at timed intervals over a 3-hour period. Desirably, the level of plasma glucose in a diabetic patient that has been treated according to the invention ranges between 160 to 60 mg/dL, between 150 to 70 mg/dL, between 140 to 70 mg/dL, between 135 to 80 mg/dL, and preferably between 120 to 80.

One skilled in the art will understand that patients treated by the methods of the invention may have been subjected to standard tests or may have been identified, without examination, as one at high risk due to the presence of one or more risk factors, such as family history, obesity, particular ethnicity (e.g., African Americans and Hispanic Americans), gestational diabetes or delivering a baby that weighs more than nine pounds, hypertension, having a pathological condition predisposing to obesity or diabetes, high blood levels of triglycerides, high blood levels of cholesterol, presence of molecular markers (e.g., presence of autoantibodies), and age (over 45 years of age). An individual is considered obese when their weight is 20% (25% in women) or more over the maximum weight desirable for their height. An adult who is more than 100 pounds overweight, is considered to be morbidly obese. Obesity is also defined as a body mass index (BMI) over 30 kg/m².

As indicated above, the methods of this invention may also be used prophylactically, i.e., in patients who are an increased risk of developing diabetes or a condition associated with diabetes. Risk factors include for example, family history of diabetes or obesity conditions, quality of nutrition, level of physical activity, presence of molecular markers of diabetes, age, race, or sex. Patients affected with other non-related disorders may also be predisposed to secondary diabetes.

One aspect of the invention provides methods of treating obesity, the method comprising administering to the subject a therapeutically effective amount of a compound described herein. In some embodiments, the compound is selected from mebendazole, cytochalasin E, deoxysappanone, nocodazole, paclitaxel, podofilox, podophyllotoxin acetate or vinblastine, or a metabolite or analog thereof. In one embodiment, the method comprises administering to the subject a microtubule modulator. Obesity is defined as a body mass index (BMI) of 30 kg/m²or more (National Institute of Health, Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults (1998)). However, the invention is also intended to include a disease, disorder, or condition that is characterized by a body mass index (BMI) of 25 kg/m²or more, 26 kg/m²or more, 27 kg/m²or more, 28 kg/m²or more, 29 kg/m²or more, 29.5 kg/m²or more, or 29.9 kg/m²or more, all of which are typically referred to as overweight (National Institute of Health, Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults (1998)).

One aspect of the invention provides methods of treating cardiovascular disease, the method comprising administering to the subject a therapeutically effective amount of a compound described herein. In some embodiments, the compound is selected from mebendazole, cytochalasin E, deoxysappanone, nocodazole, paclitaxel podofilox, podophyllotoxin acetate or vinblastine, or a metabolite or analog thereof. In one embodiment, the method comprises administering to the subject a microtubule modulator.

Cardiovascular disease includes hypertension, heart failure such as congestive heat failure or heart failure following myocardial infarction, arrhythmia, diastolic dysfunction such as left ventricular diastolic dysfunction, diastolic heart failure, or impaired diastolic filling, systolic dysfunction, ischemia such as myocardial ischemia, cardiomyopathy such as hypertrophic cardiomyopathy and dilated cardiomyopathy, sudden cardiac death, myocardial fibrosis, vascular fibrosis, impaired arterial compliance, myocardial necrotic lesions, vascular damage in the heart, vascular inflammation in the heart, myocardial infarction including both acute post-myocardial infarction and chronic post-myocardial infarction conditions, coronary angioplasty, left ventricular hypertrophy, decreased ejection fraction, coronary thrombosis, cardiac lesions, vascular wall hypertrophy in the heart, endothelial thickening, myocarditis, and coronary artery disease such as fibrinoid necrosis or coronary arteries.

In some embodiments, the heart disease is cardiomyopathy. Mitochondrial defects have been demonstrated to affect the heart, in particular leading to cardiomyopathy. (See Wallace D C, Am Heart J. 139(2 Pt 3):S70-85 (2000) and Fan, W. et al., Science 319:958-962 (2008)).

IV. Compositions
Cytoskeleton Modulators

In some embodiments of the methods described herein, the therapeutic compound that is administered to the subject is a cytoskeleton modulator. In some embodiments, the compound may modulate microfilaments, for example by promoting the polymerization or depolymerization of actin. In some embodiments, the compound may modulate microtubules, for example by promoting the polymerization or depolymerization of tubulin.

Microfilament Modulators

In some embodiments of the methods described herein, the therapeutic compound administered to the subject is a microfilament modulator. Microfilaments are polymers of actin subunits.

In one embodiment of the methods described herein, the microfilament modulator administered to the subject is a cytochalasin derivative or a metabolite or analog thereof. “Cytochalasins” include fungal metabolites exhibiting an inhibitory effect on target cellular metabolism, including prevention of contraction or migration of vascular smooth muscle cells. Preferably, cytochalasins inhibit the polymerization of monomeric actin (G-actin) to polymeric form (F-actin). Cytochalasins typically are derived from phenylalanine (cytochalasins), tryptophan (chaetoglobosins), or leucine (aspochalasins), resulting in a benzyl, indol-3-yl methyl or isobutyl group, respectively, at position C-3 of a substituted perhydroisoindole-1-one moiety (Formula V or VI). The perhydroisoindole moiety in turn contains an 11-, 13- or 14-atom carbocyclic- or oxygen-containing ring linked to positions C-8 and C-9. All naturally occurring cytochalasins contain a methyl group at C-5; a methyl or methylene group at C-12; and a methyl group at C-14 or C-16. Exemplary molecules include cytochalasin A, cytochalasin B, cytochalasin C, cytochalasin D, cytochalasin E, cytochalasin F, cytochalasin G, cytochalasin H, cytochalasin J, cytochalasin K, cytochalasin L, cytochalasin M, cytochalasin N, cytochalasin O, cytochalasin P, cytochalasin Q, cytochalasin R, cytochalasin S, chaetoglobosin A, chaetoglobosin B, chaetoglobosin C, chaetoglobosin D, chaetoglobosin E, chaetoglobosin F, chaetoglobosin G, chaetoglobosin J, chaetoglobosin K, deoxaphomin, proxiphomin, protophomin, zygosporin D, zygosporin E, zygosporin F, zygosporin G, aspochalasin B, aspochalasin C, aspochalasin D and the like, as well as functional equivalents and derivatives thereof. In certain embodiments, the cytochalasin derivative is selected from cytochalasin A, cytochalasin B, cytochalasin C, cytochalasin D, cytochalasin E, cytochalasin F, cytochalasin H, cytochalasin J, cytochalasin K, cytochalasin Q, cytochalasin R, epoxycytochalasin H and epoxycytochalasin J.

In certain embodiments, the cytochalasin derivative administered to patients is cytochalasin E or a metabolite or analogue thereof. Cytochalasin E was first discovered as a toxic metabolite of Aspergillus clavatus (Buchi et al., J Am Chem Soc. 1973; 95(16):5423-5; Demain et al. Appl Environ Microbiol. 1976; 31(1):138-40). Cytochalasin E may be obtained by isolating and purifying from the culture medium of fungi capable of producing the compound in a manner similar to that described in J. Chem. Soc. Perkin Trans. 1, p. 541 (1982), and in Agric. Biol. Chem., Vol. 53, p. 1699 (1989). Cytochalasin E depolymerizes of actin filaments by binding to high affinity sites associated with F-actin. J Biol. Chem. 1980 Feb. 10; 255(3):835-8.

Microtubule Modulators

In one embodiment of the methods described herein, the therapeutic compound that is administered to the subject is a microtubule modulator. Several compounds which affect microtubule assembly, disassembly, or function, for example through binding to or the stabilizing of microtubules, or through polymerization of tubulins to form microtubules, and the like, are known and include coumarin and dicoumarol (Jacobs, R. S. et al. U.S. Pub No. 2002/151560 A1), dictyostatin (Curran, D. P. et al., U52004186165 A1), eleutherobin (Lindel, T. et al., J. Am. Chem. Soc. 1997, 119(37), 8744-45), sarcodictyin Nicolaou, K. C., et al., WO9921862), epothilones (Goodin, S., et al., J. Gun Oncology, 2004, 22(10), 2015-25), FR182877 (Sato, B. et al., WO9632402), laulimalide and isolaulimalide (Mooberry, S. L., et al., Cancer Research, 1999, 59(3), 653-60), peloruside (Gaitanos, T. N., et al., Gancer Research, 2004, 64(15), 5063-67; and De Brabander, J. and Liao, X., US2004235939 A1), taccalonolides (Hemscheidt, T. K. and Mooberry, S. L., WO0071563), tubercidin (Mooberry, S. L., et al., Gancer Letters (Shaimon, Ireland), 1995, 96(2), 26 1-6), taxol and its analogs (Trojanowski, J. Q. and Lee, V. U.S. Pat. No. 5,580,898, 1996), discodermolide (Hung, D. T., et al., Chemistry and Biology, 1996, 3(4), 287-93; Haar, B., et al. Biochemistry, 1996, 35(1), 243-50; Kowaiski, R. L., et al., Molec. Pharm., 1997, 52, 6 13-22), and its analogs (Smith, et al., U.S. Pub No. 2002/0103387 A1 and PCT U502/24932), and the like, the reference each of which is hereby incorporated herein by reference, in its entirety. PCT Pub No. WO06/091728A2 discloses microtubule stabilizing compounds.

In one embodiment, the microtubule modulator is a microtubule stabilizing compound selected from coumarin, dicoumarol, dictyostatin, discodermolide, eleutherobin, sarcodictyin A or B, epothilone, FR182877, laulimalide, isolaulirnalide, peloruside, taccalonolide, or tubercidin, or any analog, or any combination, or both, thereof. In one embodiment, the anti-microtubule agent is selected from taxanes, discodermolide, colchicine, vinca alkaloids, and analogues or derivatives of any of these.

In one embodiment, the microtubule stabilizing agent effectively stabilizes microtubules at a physiologically compatible concentration. Microtubule stabilization typically is measured using a dose-response assay in which a sensitive assay system is contacted with a compound of interest over a range of concentrations at which no or minimal effect is observed, through higher concentrations at which partial effect is observed, to saturating concentrations at which a maximum effect is observed. Theoretically, such assays of the dose-response effect of stabilizer compounds can be expressed as a curve, expressing a degree of stabilization as a function of concentration. The curve also theoretically passes through a point at which the concentration is sufficient to stabilize microtubules to a level that is 50% that of the difference between minimal and maximal activity in the assay. This concentration is defined as the Inhibitory Concentration (50%) or IC₅₀Comparisons between the efficacy of stabilizers often are provided with reference to comparative IC₅₀concentrations, wherein a higher IC₅₀indicates that the test compound is less potent, and a lower IC₅₀indicates that the compound is more potent, than a reference compound. Similarly, the potency of stabilizer compounds can be related in terms of the Effective Concentration (50%) or EC₅₀, which is a measure of dose-response activity in a cell-based or animal-based model. EC₅₀measurements are useful to relate properties of the compound that can influence its clinical utility, such as compound solubility, ability to penetrate cell membranes, partition coefficient, bioavailability, and the like. Two compounds can exhibit a divergence in comparative IC₅₀and EC₅₀values, i.e., one compound can be more potent in a biochemical assay and the second compound more potent in a cell-based assay simply due to different properties of the compounds.

In certain embodiments of the methods described herein, the microtubule modulator is represented by the structure of Formula (I):

In one embodiment of the methods described herein, the therapeutic compound that is administered to the subject is methyl[5-benzoyl-benzimidazol-2-carbamate] (mebendazole) or a metabolite or analog thereof. In one embodiment, mebendazole is administered to a subject not afflicted with, or at risk of being afflicted with, a worm infection, including hookworm infection, a roundworm infection, a pinworm infection or a whipworm infection. In one embodiment, mebendazole is administered to a subject not afflicted with diabetes. Commercially-available compositions that may be used in the methods of the invention include Ovex®, Vermox®, Antiox® or Pripsen®. In one embodiment, the mebendazole is administered as oral tablets, such as 100 mg chewable tablets. U.S. Patent Pub No. 2005/0038096 discloses mebendazole containing compositions that may be used in the methods described herein. Mebendazole is also described in Campell, W. C. et al. J. Parasitol. 61:844-852 (1975); Heath, D. D. et al. Parasitology 70:273-285 (1975). Mebendazole is a tubulin inhibitor.

In one embodiment of the methods described herein, the therapeutic compound that is administered to the subject is methyl[5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl]carbamate (nocodazole) or a metabolite or analog thereof. Nocodazole is a microtubule inhibitor that prevents the addition of tubulin molecules to microtubules, thereby disturbing the equilibrium and leading to microtubule depolymerization and destruction of the spindle. Nocodazole may be obtained from Sigma-Aldrich.

In one embodiment of the methods described herein, the therapeutic compound that is administered to the subject is selected from albendazole, fenbendazole, oxfendazole, oxibendazole, methiazole, and parbendazole.

In certain aspects of the methods described herein, the therapeutic compound administered to the subject is represented by the structure of Formula (II):

wherein R¹is selected from H or methyl and R²is selected from H or hydroxy. In certain embodiments, the therapeutic compound administered to the subject is selected from a compound represented by a structure of Formulas (III)-(VI):

In certain embodiments, the therapeutic compound administered to the subject is the compound of Formula (V), deoxysappanone B, or a metabolite, analog or derivative thereof. In one embodiment, deoxysappanone (B) is selected from deoxysappanone (B) 7,3′-dimethyl ether; deoxysappanone (B) 7,3′-trimethyl ether; sappanone (A) trimethyl ether; 3-deshydroxysappanol trimethyl ether; sappanone (A) 7-methyl ether; tetrahydrosappanone (A) trimethyl ether; sappanone (A) dimethyl ether; and deoxysappanone (B) 7,3′-dimethyl ether acetate. In one embodiment, the therapeutic compound administered to the subject is deoxysappanone (B) 7,3′-dimethyl ether, sappanone (A) trimethyl ether, or 3-deshydroxysappanol trimethyl ether. In one embodiment, deoxysappanone B, or a metabolite, analog or derivative thereof is administered to a subject not afflicted with diabetes.

In certain embodiments, the therapeutic compound administered to the subject is represented by the structure of Formula (VII):

wherein, R is nitrogen or acetyl and one of R¹and R²is hydroxy and the other is selected from t-butylcarbonylamino or benzoylamino. In one embodiment of the methods described herein, the therapeutic compound that is administered to the subject is paclitaxel (Taxol) or a metabolite or analog thereof. Paclitaxel is an anti-microtubule agent extracted from the needles and bark of the Pacific yew tree. U.S. Patent Pub No. 2006/0281933 provides a method of synthesizing paclitaxel. Paclitaxel may be formulated as a concentrated solution containing paclitaxel, 6 mg per milliliter of Cremophor EL (polyoxyethylated castor oil) and dehydrated alcohol (50% v/v) and must be further diluted before administration (Goldspiel, “Taxol pharmaceutical issues: preparation, administration, stability, and compatibility with other medications,”]Ann. Pharmacotherapy, 28:S23-26, 1994.).

In one embodiment, a soluble paclitaxel form of paclitaxel is administered that includes solubilizing moieties such as succinate, sulfonic acid, amino acids; and phosphate derivatives at the 2′-hydroxyl group or at the 7-hydroxyl position (Deutsch et al., “Synthesis of congeners and prodrugs. Water-soluble prodrugs of paclitaxel with potent antitumor activity,” J. Med. Chem., 32:788-792, 1989; Mathew et al., “Synthesis and evaluation of some water-soluble prodrugs and derivatives of taxol with antitumor activity,” J. Med. Chem., 35:145-151, 1992; Nicolaou, Riemer, Kerr, Rideout, Wrasidio, “Design, synthesis and biological activity of protaxols,” Nature, 364:464-466, 1993; Vyas et al., “Phosphatase-activated prodrugs of paclitaxel,” In: Taxane Anticancer Agents: Basic Science and Current Status, Georg, Chen, Ojima, Vyas. eds., American Chemical Society, Washington, D.C., 124-137, 1995; Rose, et al., “Preclinical antitumor activity of water-soluble paclitaxel derivatives,” Cancer Chemother. Pharmacol., 39:486-492, 1997).

Additional derivatives and analogs of paclitaxel, as well as formulations, that may be used in methods of the invention are described in U.S. Patent Pub Nos: 2006/0135404, 2006/0052312, 2004/0198638, 2003/0176320, 2003/0166507, 2003/0147807, 2003/0134793, 2003/0130341, 2003/0130178, 2003/0130170, 2003/0124055, 2003/0114518, 2003/0114397, 2003/0114363, 2003/0113335, 2005/0191323, 2005/0016926, 2002/0103254. Paclitaxel is commercially available as Onxol® and Taxol®.

In one embodiment of the methods described herein, the therapeutic compound that is administered to the subject is podofilox or a metabolite or analog thereof. Podofilox, also called podophyllotoxin, is a purer and more stable form of podophyllin in which only the biologically active portion of the compound is present. Like podophyllin, it is used to treat genital warts. It has several advantages of podophyllin, however. Podofilox is commercially available as Condylox®, and it is manufactured by Oclassen Pharmaceuticals.

In one embodiment of the methods described herein, the therapeutic compound that is administered to the subject is podophyllotoxin acetate or a metabolite or analog thereof. Podophyllotoxin is a well-known lignan which has been isolated from plant extracts, particularly from so-called Podophyllum resins obtained by solvent extraction of various parts—notably the roots and rhizomes—of plants of the genus Podophyllum, e.g. the North American species Podophyllum peltatum and the Indian species Podophyllum emodi. Podophyllotoxin has been reported to occur in a variety of polymorphic forms having different melting points, and in the form of various solvates [see, e.g., A. W. Schrecker et al., J. Org. Chem. 21 (1956) 288]. Schrecker et al. recognized at least four crystalline modifications of podophyllotoxin: (A), with water (m.p. 161° C.-162° C.); (B), unsolvated (m.p. 183° C.-184° C.); (C), with water and benzene of crystallization (m.p. 114° C.-118° C. “foaming”); and (D), unsolvated (m.p. 188° C.-189° C.). U.S. Patent Pub. 2006/0293254 describes a podophyllotoxin that may be used in the treatments described herein. U.S. Pat. No. 5,315,016 discloses a process for preparing pure podophyllotoxin. U.S. Pat. No. 4,680,399: discloses a process for the isolation and purification of podophyllotoxin. PCT Pub. No. WO01/52826A2 discloses podophyllotoxin compositions. U.S. Pat. No. 5,336,605 discloses the production of podophyllotoxins using podophyllum.

In certain embodiments, the therapeutic compound administered to the subject is represented by the structure of Formula (VIII):

In one embodiment of the methods described herein, the therapeutic compound that is administered to the subject is vinblastine or a metabolite or analog thereof. Vinblastine inhibits palmitoylation of tubulin and is therefore a microtubule inhibitor. PCT Pub. No. WO88/03135 discloses a method of isolating vinblastine. U.S. Pat. No. 4,749,787 discloses a process for isolating vinblastine from the plant catharanthis roseus. U.S. Pub No. 2006/0293357 discloses intermediates for synthesis of vinblastine, a process for preparation of the intermediates and a process for synthesis of vinblastines. U.S. Pat. No. 5,397,784 discloses stable parenteral compositions of vinblastine or vincristine. U.S. Pat. No. 4,870,162 discloses conjugates of vinblastine, a process for their preparation and their use in therapy. U.S. Pat. No. 4,910,138 discloses the use of an organ culture of Catharanthus roseus to produce vincristine and vinblastine. U.S. Pat. No. 4,639,456 discloses vinblastin-23-oyl amino acid derivatives. U.S. Pat. No. 4,362,664 discloses vinblastine oxazolidinedione disulfides and related compounds. U.S. Pat. No. 4,305,875 discloses a process for the synthesis of vinblastine and leurosidine. U.S. Pat. No. 4,188,394 discloses ophthalmic compositions of vinblastine. In certain embodiments, the therapeutic compound that is administered to the subject is vincristine.

V. Screening Methods

One aspect of the invention provides for methods for identifying compounds that enhance mitochondrial function. Mitochondrial function can be evaluated based on a number of criteria. These include mitochondrial respiratory activity, which may decrease when mitochondrial function is impaired, and mitochondrial membrane potential, which may decrease when mitochondrial function is impaired.

The methods disclosed herein provide assaying for the effect of one or more compounds on OXPHOS gene expression and mitochondrial function and correlating the effect determined from those assays on mitochondrial function. An increase in OXPHOS gene expression and an increase in mitochondrial function are indicative of compounds that enhance mitochondrial function.

In some embodiments, the mitochondrial function is assayed by measuring reactive oxygen species (ROS), and an increase in OXPHOS gene expression and a decrease in ROS is indicative of a compound that enhances mitochondrial function. In some embodiments, the method further comprises assaying for the effect of one or more compounds on cell viability. In some embodiments, the method further comprises assaying for the effect of one or more compounds on dehydrogenase activity, mitochondrial membrane potential, cellular ATP, and cytochrome c protein.

Examples 1 and 2 provide exemplary embodiments of methods for identifying compounds than enhance mitochondrial function.

One aspect of the invention provides for methods for identifying compounds useful in treating a disorder characterized by mitochondrial dysfunction in a subject. The methods comprise assaying for the effect of one or more compounds on OXPHOS gene expression and mitochondrial function and correlating the effect determined from those assays on mitochondrial function. An increase in OXPHOS gene expression and an increase of mitochondrial function are indicative of compounds useful in treating a disorder.

In some embodiments, the mitochondrial function is assayed by measuring reactive oxygen species (ROS) and an increase in OXPHOS gene expression and a decrease in ROS is indicative of a compound that enhances mitochondrial function. In some embodiments, the method further comprises assaying for the effect of one or more compounds on cell viability. In some embodiments, the method further comprises assaying for the effect of one or more compounds on dehydrogenase activity, mitochondrial membrane potential, cellular ATP, and cytochrome c protein.

Examples 1 and 2 provide exemplary embodiments of methods for identifying compounds that enhance mitochondrial function.

In some embodiments of the screening methods, the disorder characterized by mitochondrial dysfunction is MELAS (Mitochondrial Encephalomyopathy Lactic Acidemia and Stroke-like episodes), MERRF (Myoclonic Epilepsy with “Ragged Red” (muscle) Fibers), NARP (Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa), LHON (Leber's Hereditary Optic Neuropathy), Leigh's Syndrome (Subacute Necrotizing Encephalomyopathy), PEO (Progressive External Opthalmoplegia), and Keams-Sayres Syndrome (PEO, pigmentary retinopathy, ataxia, and heart-block). In some embodiments, the disorder characterized by mitochondrial dysfunction is diabetes. In some embodiments, the disorder characterized by mitochondrial dysfunction is type II diabetes mellitus. In some embodiments, the disorder characterized by mitochondrial dysfunction is cardiomyopathy. In some embodiments, the disorder characterized by mitochondrial dysfunction is Parkinson's disease. In some embodiments, the disorder characterized by mitochondrial dysfunction is Huntington's disease. In some embodiments, the disorder characterized by mitochondrial dysfunction is premature aging.

One aspect of the invention provides for methods for determining compounds that are contraindicated in a subject. A compound is contraindicated when administration increases the risk in a subject of suffering negative consequences. A contraindication may be absolute, i.e. the compound should never be administered to a subject, or relative, i.e., the risks involved must be balanced against each other. It is within the purview of one skilled in the art to examine the risk of administering compounds identified in this screen and determine on an individual patient basis whether the risk is acceptable or not.

The methods comprise assaying for the effect of one or more compounds on dehydrogenase activity and cell viability and correlating the effect determined from those assays to a contraindication of a compound. A decrease in cellular dehydrogenase activity absent a decrease in cell viability indicates that the compound is contraindicated. In some embodiments, the effect of one or more compounds on cellular ATP is also determined and a decrease in ATP levels indicates that the compound is contraindicated.

In some embodiments, the method further comprises assaying for the effect of one or more compounds on mitochondrial membrane potential, OXPHOS gene expression, reactive oxygen species and cytochrome c protein. A decrease in membrane potential, an decrease in OXPHOS gene expression, an increase in ROS, and a decrease in cytochrome c levels are all indicators that suggest the compound is contraindicated.

In some embodiments, the subject is afflicted with a disorder characterized by mitochondrial dysfunction.

One aspect of the invention provides for determining two or more compounds that are contraindicated for joint administration to a subject. As demonstrated in Example 4, propranolol has an additive effect on statin-induced decrease in ATP levels. The screening methods described herein, provide for determining compounds that when jointly administered impair mitochondrial function.

The methods comprise assaying for the effect of two or more compounds on dehydrogenase activity and cell viability and correlating the effect determined from those assays to a contraindication of a combination of compounds. A decrease in cellular dehydrogenase activity absent a decrease in cell viability in two or more compounds indicates that administration of the two or more compounds are contraindicated. In some embodiments, the effect of two or more compounds on cellular ATP is also determined and a decrease in ATP levels indicates that the administration of the combination of compounds is contraindicated.

In some embodiments, the method further comprises assaying for the effect of two or more compounds on mitochondrial membrane potential, OXPHOS gene expression, reactive oxygen species and cytochrome c protein. A decrease in membrane potential, an decrease in OXPHOS gene expression, an increase in ROS, and a decrease in cytochrome c levels are all indicators that suggest the combination of compounds is contraindicated.

In some embodiments, the subject is afflicted with a disorder characterized by mitochondrial dysfunction.

In some embodiments of the methods, the subject is afflicted with MELAS (Mitochondrial Encephalomyopathy Lactic Acidemia and Stroke-like episodes), MERRF (Myoclonic Epilepsy with “Ragged Red” (muscle) Fibers), NARP (Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa), LHON (Leber's Hereditary Optic Neuropathy), Leigh's Syndrome (Subacute Necrotizing Encephalomyopathy), PEO (Progressive External Opthalmoplegia), and Keams-Sayres Syndrome (PEO, pigmentary retinopathy, ataxia, and heart-block). In some embodiments, the subject is afflicted with diabetes. In some embodiments, the subject is afflicted with type II diabetes mellitus. In some embodiments, the subject is afflicted with cardiomyopathy. In some embodiments, the subject is afflicted with Parkinson's disease. In some embodiments, the subject is afflicted with Huntington's disease. In some embodiments, the subject is afflicted with premature aging.

The methods described herein utilize a variety of cell-based assays. Such a cell may be a primary cell in culture or it may be a cell line. In some embodiments, the cells are murine myotubes. In some embodiments, the cells are seeded in multiwell plates and allowed to reach log phase growth.

Once the cell cultures are thus established, various concentrations of the compound being tested are added to the media and the cells are allowed to grow exposed to the various concentrations for 6, 12, 24, 36, 48 or more hours. It should be noted that testing the specific compounds for longer or shorter periods of time is contemplated to be within the scope of the invention. Increased culture times may sometimes reveal additional cytotoxicity information at the cost of slowing down the screening process.

Furthermore, the cells may be exposed to the test compound at any given phase in the growth cycle. For example, in some embodiments, it may be desirable to contact the cells with the compound at the same time as a new cell culture is initiated. Alternatively, it may be desirable to add the compound when the cells have reached confluent growth or arc in log growth phase. Determining the particular growth phase cells are in is achieved through methods well known to those of skill in the art.

In an exemplary set of assays, the test compound concentration range comprises dosing solutions which yield final growth media concentration of 0.05 micromolar, 0.1 micromolar, 1.0 micromolar, 5.0 micromolar, 10.0 micromolar, 20.0 micromolar, 50.0 micromolar, 100 micromolar, and 300 micromolar of the compound in culture media. As mentioned, these are exemplary ranges, and it is envisioned that any given assay will be run in at least two different concentrations, and the concentration dosing may comprise, for example, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more concentrations of the compound being tested. Such concentrations may yield, for example, a media concentration of 0.05 micromolar, 0.1 micromolar, 0.5 micromolar, 1.0 micromolar, 2.0 micromolar, 3.0 micromolar, 4.0 micromolar, 5.0 micromolar, 10.0 micromolar, 15.0 micromolar, 20.0 micromolar, 25.0 micromolar, 30.0 micromolar, 35.0 micromolar, 40.0 micromolar, 45.0 micromolar, 50.0 micromolar, 55.0 micromolar, 60.0 micromolar, 65.0 micromolar, 70.0 micromolar, 75.0 micromolar, 80.0 micromolar, 85.0 micromolar, 90.0 micromolar, 95.0 micromolar, 80.0 micromolar, 110.0 micromolar, 120.0 micromolar, 130.0 micromolar, 140.0 micromolar, 150.0 micromolar, 160.0 micromolar, 170.0 micromolar, 180.0 micromolar, 190.0 micromolar, 200.0 micromolar, 210.0 micromolar, 220.0 micromolar, 230.0 micromolar, 240.0 micromolar, 250.0 micromolar, 260.0 micromolar, 270.0 micromolar, 280.0 micromolar, 290.0 micromolar, and 300 micromolar in culture media. It will be apparent that a cost-benefit balancing exists in which the testing of more concentrations over the desired range provides additional information, but at additional cost, due to the increased number of cell cultures, assay reagents, and time required. In one embodiment, ten different concentrations over the range of 0 micromolar to 300 micromolar are screened.

Assays that measure mitochondrial physiology are indicators of mitochondrial function. Compounds that alter mitochondrial function may either up- or down regulating oxidative respiration. It should be noted that the screening methods provided herein allow for compounds to be screened using a number of different assays. This permits a more accurate prediction of the compound's in vivo effects. It should be noted that for some compounds the assays may provide conflicting results. It is within the purview of one skilled in the art to analyze the results of the assays in their entirety and reach a conclusion as to the compound's overall effects.

One assay provided by the invention measures changes in OXPHOS gene expression. The assay to measure changes in OXPHOS gene expression may measure the changes of any number of OXPHOS genes, as described in Mootha, V. K., et al., Nat. Genet. 34: 267-273 (2003). In some embodiments, the assay measures the changes in expression of the following genes (a) Mt-Atp6 (Entrez GeneID numbers 17705 or 4508), (b) Mt-Atp8 (Entrez GeneID numbers 17706 or 4509), (c) Mt-Co1 (Entrez GeneID numbers 17708 or 4512), (d) Mt-Co2 (Entrez GeneID numbers 17709 or 4513), (e) Mt-Co3 (Entrez GeneID numbers 17710 or 4514), (f) Mt-Cytb (Entrez GeneID number 17711 or 4519), (g) Mt-Nd1 (Entrez GeneID numbers 17716 or 4535), (h) Mt-Nd2 (Entrez GeneID numbers 17717 or 4536), (i) Mt-Nd3 (Entrez GeneID numbers 17718 or 4537), (j) Mt-Nd4 (Entrez GeneID numbers 17719 or 4538), (k) Mt-Nd41 (Entrez GeneID numbers 17720 or 4539), (l) Mt-Nd5 (Entrez GeneID numbers 17721 or 4540), (m) Mt-Nd6 (Entrez GeneID numbers 17722 or 4541), (n) Atp5a1 (Entrez GeneID numbers 11946 or 498), (o) Atp5c1 (Entrez GeneID numbers 11949 or 509), (p) Atp5o (Entrez GeneID numbers 28080 or 539), (q) Cox5b (Entrez GeneID numbers 12859 or 1329), (r) Cox7a2 (Entrez GeneID numbers 12866 or 1347), (s) Cyc1 (Entrez GeneID numbers 66445 or 1537), (t) Hspc051 (Entrez GeneID number 66152 or 29796), (u) Ndufa5 (Entrez GeneID numbers 68202 or 4698), (v) Ndufb5 (Entrez GeneID numbers 66046 or 4711), (w) Sdhd (Entrez GeneID numbers 66925 or 6392), (x) Uqcrb (Entrez GeneID numbers 67530 or 7381), and (y) Uqcrc1 (Entrez GeneID numbers 22273 or 7384).

In some embodiments, expression of OXPHOS genes is measured using a system designed to assess the presence and/or the quantity of any given transcript. In some embodiments, the system can be used for thousands of samples. In some embodiments, primer pairs are used to amplify a target sequence on an OXPHOS gene. The target sequence may be the entire gene or any appropriate region thereof. In some embodiments, the primer pairs may comprise nucleic acids that bind under stringent conditions to the target sequences. In other embodiments, the primer pairs may be linked to tag sequences. In some embodiments, tag sequences may be any nucleic acid sequence that does not hybridize to the target sequence. In certain embodiments, tag sequences may be selected from a set of over 100 sequences that are known in the art. In some embodiments, the primer pairs may also be linked to an additional nucleic acid sequence. In some embodiments, the primer pairs will be linked to tag sequences and tag sequences will be further linked to additional nucleic acid sequences. In some embodiments, the additional nucleic acid sequence will not hybridize to either the target sequence or the tag sequences. In some embodiments, the tag sequence will be linked to the 5′ end of the primer in the primer pair. In some embodiments, the additional nucleic acid sequence will be linked to the 5′ end of the tag sequence. In certain embodiments, the additional nucleic acid sequences will comprise binding sites for universal primers. In some embodiments, universal primers are sequences that may be used to amplify simultaneously all desired targets in a reaction mix. In some embodiments, universal primers may be selected from nucleic acid sequences that are found in humans, non-human mammals, plants, fungi, bacteria, or viruses. In some embodiments, universal primers are derived from the DNA sequence of a bacteriophage, such as the promoter for the RNA polymerases T7, SP6, or T3. Any nucleic acid sequences in all embodiments may also be further modified by addition or removal of groups such as phosphates, methyl groups, or labels known in the art.

In some embodiments, target sequences are identified in a pool of transcripts isolated from a sample. In some embodiments, the transcripts may be captured by binding to immobilized poly-dT. In other embodiments, a plurality of primers that hybridizes under stringent conditions to the target sequences is added. Copies of the target sequences are produced from the primers, using reverse transcriptase and ligase. In some embodiments, each primer further comprises a tag sequence linked to the primer, such that the resultant copy of the target sequence contains at least one copy of a tag sequence. In some embodiments, the tag sequence is linked to the 5′ end of the primer. In other embodiments, each primer is linked to a tag sequence plus an additional nucleic acid sequence, such as a site complementary to a universal primer, and the resultant copy of the target sequence contain at least one copy of a tag sequence and is flanked by sites for universal primers. In some embodiments, a pair of universal primers can then be used to amplify the copies of the target sequences. In some embodiments, one of the universal primers is phosphorylated, and the other is linked to a binding moiety. Thus, a final amplification product is produced in these embodiments, wherein the amplification product contains the following nucleic acid sequences: (1) at least one portion of the target sequence, (2) a tag sequence, (3) universal primer sites, and (4) a binding moeity. In some embodiments, detection of the final amplification product requires the binding of the tag sequence to a complementary nucleic acid sequence that has been conjugated to a detectable moiety. In some embodiments, the detectable moiety is a microsphere. In further embodiments, the microsphere is colored, such that a reaction mix containing more than one colored microsphere can be distinguished from others by flow cytometry.

In other embodiments, the levels of OXPHOS gene expression are quantified by measuring the quantity of the amplification products. In some embodiments, the binding moieties on the amplification products are measured. Examples of binding moieties include but are not limited to proteins, epitope tags, small molecules, aptamers, nucleic acid sequences, proteins and antibodies to any of the preceding. In some embodiments, the binding moieties are biotin, avidin, or streptavidin. In other embodiments, the quantity of the binding moiety is determined indirectly, for example, by quantifying a second binding moiety that attaches to the binding moiety. In some embodiments, the second binding moiety is conjugated to a label such as a fluorescent, enzymatic, chemilumiscent, or calorimetric label, which can then be detected by a laser scanner, or CCD camera, or X-ray film, depending on the label, or other appropriate means of detecting a particular label, and quantified. Examples of labels include but are not limited to molecules such as fluorescein, Eosin Y, Rhodamine, Rose Bengal, Sulforhodamine, acridine yellow, proflavin, DDAO, cresyl violet, nile blue, oxazine, Cy2, Cy3, Cy5, Cy7, Alexa Fluors, coumarin, chlorophyll; fluorescent proteins such as DsRed, GFP and variations of GFP such as EGFP, YFP, CFP, RFP; phycocyanin, phycoerythrin; molecules such as luciferase, digoxygenin, alkaline phosphatase, and HRP.

In some embodiments, the expression level of genes is weighted to determine a Composite Z-score. Each gene is weighted by its ability to distinguish DMSO control wells from PGC-1α-treated wells. The signal-to-noise ratio of each gene is calculated using a PGC-α-treated positive control and DMSO negative control. The expression value of each gene per well is multiplied by this signal-to-noise ratio. The weighted scores are summed over nuclear-encoded or mitochondrial-encoded OXPHOS genes to derive one score each for expression within each genome. The Composite Z-score is exemplified in the tables as GE-HTS. In some embodiments, an increase in OXPHOS gene expression is a GE-HTS value greater than 0.5, 1.0, 1.5, 1.8, 2.0, 2.2, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, or 3.6. In some embodiments, a decrease in OXPHOS gene expression is a GE-HTS value less than 1.0, 0.5, 0.3, 0.0, −0.1, −0.2, −0.5, −0.8, −1.0, −1.2, −1.5, −2.0, −2.5, or −3.0.

One assay useful in the methods described herein is an assay to measure reactive oxygen species. Biologically reactive oxygen species include, but are not limited to: i) superoxide (O₂); ii) peroxides (ROOH) such as, but not limited to, hydrogen peroxide (H₂O₂) or hypochlorite (OCl⁻); and iii) hydroxide radical (OH). Biologically reactive nitrogen species include, but are not limited to, nitric oxide (NO), nitrogen dioxide (NO₂), or peroxynitrate (ONOO⁻). In the candidate screening assays H₂O₂/free radical measurement may be measured using kits (kit available from Molecular Probes-Invitrogen) or reporter molecule undergoing conformational change in the presence of free radical/H₂O₂(quantitative fluorescent output). A Composite Z-score is determined as described above (see also on the World Wide Web at chembank.broad.harvard.edu/details.htm?tag=Help#screeningData). A Composite Z-score is exemplified in the tables as ROS. In some embodiments, an increase in ROS is a score greater than 0.5, 1.0, 1.5, 1.8, 2.0, 2.2, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, or 3.6. In some embodiments, a decrease in ROS is a score less than 1.0, 0.5, 0.3, 0.0, −0.1, −0.2, −0.5, −0.8, −1.0, −1.2, −1.5, −2.0, −2.5, or −3.0.

Another example of an assay that measures mitochondrial physiology is an assay for mitochondrial membrane potential. Typically, mitochondrial membrane potential may be determined according to methods with which those skilled in the art will be readily familiar, including but not limited to detection and/or measurement of detectable compounds such as fluorescent indicators, optical probes and/or sensitive pH and ion-selective electrodes (See, e.g., Ernster et al., 1981 J. Cell Biol. 91:227s and references cited; see also Haugland, 1996 Handbook of Fluorescent Probes and Research Chemicals, Sixth Ed., Molecular Probes, Eugene, Oreg., pp. 266-274 and 589-594.). For example, by way of illustration and not limitation, the fluorescent probes 2-,4-dimethylaminostyryl-N-methylpyridinium (DASPMI) and tetramethylrhodamine esters (e.g., tetramethylrhodamine methyl ester, TMRM; tetramethylrhodamine ethyl ester, TMRE) or related compounds (see, e.g., Haugland, 1996, supra) may be quantified following accumulation in mitochondria, a process that is dependent on, and proportional to, mitochondrial membrane potential (see, e.g., Murphy et al., 1998 in Mitochondria & Free Radicals in Neurodegenerative Diseases, Beal, Howell and Bodis-Wollner, Eds., Wiley-Liss, New York, pp. 159-186 and references cited therein; and Molecular Probes On-line Handbook of Fluorescent Probes and Research Chemicals, on the world wide web at probes.com/handbook/toc.html). Other fluorescent detectable compounds that may be used include but are not limited to rhodamine 123, rhodamine B hexyl ester, DiOC.sub.6(3), JC-1 [5,5′,6,6′-Tetrachloro-1,1′,3,3′-Tetraethylbezimidazolcarbocyanine Iodide] (see Cossarizza, et al., 1993 Biochem. Biophys. Res. Comm. 197:40; Reers et al., 1995 Meth. Enzymol. 260:406), rhod-2 (see U.S. Pat. No. 5,049,673; all of the preceding compounds are available from Molecular Probes, Eugene, Oreg.) and rhodamine 800 (Lambda Physik, GmbH, Gottingen, Germany; see Sakanoue et al., 1997 J. Biochem. 121:29). Methods for monitoring mitochondrial membrane potential are also disclosed in U.S. patent application Ser. No. 09/161,172. A Composite Z-score is determined as described above (see also on the World wide Web at chembank.broad.harvard.edu/details.htm?tag=Help#screeningData). A Composite Z-score for mitochondrial membrane potential measured using the JC-1 assay is exemplified in the tables as ΔΨ_m. In some embodiments, an increase in mitochondrial membrane potential is a score greater than 0.5, 1.0, 1.5, 1.8, 2.0, 2.2, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, or 3.6. In some embodiments, a decrease in membrane potential is a score less than 1.0, 0.5, 0.3, 0.0, −0.1, −0.2, −0.5, −0.8, −1.0, −1.2, −1.5, −2.0, −2.5, or −3.0.

Another example of an assay that measures mitochondrial physiology is an assay for cellular ATP levels. ATP can provide information on the energy status of the cell and provides a marker to assess early changes in mitochondrial function. Assays that allow a determination of ADP/ATP energy balance are well known in the art (Kangas et al., Med Biol, 62, 338-343, 1984). A Composite Z-score is determined as described above (see also on the World Wide Web at chembank.broad.harvard.edu/details.htm?tag=Help#screeningData). A Composite Z-score for the cellular ATP levels is exemplified in the tables as ATP. In some embodiments, an increase in cellular ATP levels is a score greater than 0.5, 1.0, 1.5, 1.8, 2.0, 2.2, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, or 3.6. In some embodiments, a decrease in cellular ATP levels is a score less than 1.0, 0.5, 0.3, 0.0, −0.1, −0.2, −0.5, −0.8, −1.0, −1.2, −1.5, −2.0, −2.5, or −3.0.

Mitochondria physiology and function can also be evaluated by measuring mitochondrial dehydrogenase activity. In one embodiment, mitochondrial dehydrogenase activity is measured using the MTT assay. Mitochondria catalyze the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to a blue or purple formazan compound. The relatively insoluble formazan blue is extracted into isopropanol and the absorbance of the extract measured. A high absorbance value indicates viable cells and functional mitochondria. Conversely, a decrease in the intensity of color suggests either a loss of cells, or direct toxic effects on the mitochondria. The MTT assay is well known to those of skill in the art and has been described in for example, the MTT mitochondrial dye assay is described in Mosmann, J. Immunol. Methods 65, 55-63, 1983 and in Denizot et al., J. Immunol. Methods. 89, 271-277, 1986. A Composite Z-score is determined as described above (see also World Wide Web at chembank.broad.harvard.edu/details.htm?tag=Help#screeningData). A Composite Z-score for the dehydrogenase assay is exemplified in the tables as MTT. In some embodiments, an increase in dehydrogenase activity is a score greater than 0.5, 1.0, 1.5, 1.8, 2.0, 2.2, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, or 3.6. In some embodiments, a decrease in dehydrogenase activity is a score less than 1.0, 0.5, 0.3, 0.0, −0.1, −0.2, −0.5, −0.8, −1.0, −1.2, −1.5, −2.0, −2.5, or −3.0.

A further exemplary assay measures cytochrome c protein levels. A Composite Z-score is determined as described above (see also on the World Wide Web at chembank.broad.harvard.edu/details.htm?tag=Help#screeningData). A Composite Z-score for the cytochrome c assay is exemplified in the tables as cyt c. In some embodiments, an increase in cytochrome c levels is a score greater than 0.5, 1.0, 1.5, 1.8, 2.0, 2.2, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, or 3.6. In some embodiments, a decrease in cytochrome c levels is a score less than 1.0, 0.5, 0.3, 0.0, −0.1, −0.2, −0.5, −0.8, −1.0, −1.2, −1.5, −2.0, −2.5, or −3.0.

An additional assay useful in the screening methods described herein is a cell viability assay. This assay distinguishing between compounds that are generally toxic to a cell versus those with a more specific effect on mitochondrial function. Cell viability assays are widely known to one skilled in the art. In one embodiment, the assay utilizes calcein dye. A Composite Z-score is determined as described above (see also on the World Wide Web at chembank.broad.harvard.edu/details.htm?tag=Help#screeningData). A Composite Z-score for the cell viability assay is exemplified in the tables as Viability. In some embodiments a lack of a decrease on cell viability is a score greater than −0.5, 0.0, 0.5, 1.0, 1.5, 1.8, 2.0, 2.2, 2.4, 2.6, 2.8, 3.0

High throughput assays for screening numerous compounds are specifically contemplated. In certain embodiments, the high throughput screens may be automated. In high throughput screening assays, groups of compounds are exposed to a biological target. These groups may be assembled from collections of compounds previously individually prepared and since stored in a compound bank, the assembly being random or guided by the use of similarity programs from which similar structures are formed. The assays provided herein are optimized to be used in a high throughput format. In some embodiments the assays are performed in a multi-well plate. In some embodiments, the assays are performed in a 384-well plate.

In certain aspects of the present invention, all the necessary components for conducting the assays may be packaged into a kit. Specifically, the present invention provides a kit for use in an assay, the kit comprising a packaged set of reagents for conducting two or more assays selected from the group consisting of a OXPHOS gene expression assay, cell viability assay, mitochondrail membrane potential assay, cellular ATP assay, dehydrogenase assay, ROS assay, and cytochrome C detection assay. In addition to the reagents, the kit may also include instructions packaged with the reagents for performing one or more variations of the assays of the invention using the reagents. The instructions may be fixed in any tangible medium, such as printed paper, or a computer-readable magnetic or optical medium, or instructions to reference a remote computer data source such as a worldwide web page accessible via the internet.

In some embodiments, a kit is provided for determining OXPHOS gene expression, comprising a set of primer pairs, each pair amplifying an OXPHOS gene selected from a group consisting of the following: (a) Mt-Atp6 (Entrez GeneID numbers 17705 or 4508), (b) Mt-Atp8 (Entrez GeneID numbers 17706 or 4509), (c) Mt-Co1 (Entrez GeneID numbers 17708 or 4512), (d) Mt-Co2 (Entrez GeneID numbers 17709 or 4513), (e) Mt-Co3 (Entrez GeneID numbers 17710 or 4514), (f) Mt-Cytb (Entrez GeneID number 17711 or 4519), (g) Mt-Nd1 (Entrez GeneID numbers 17716 or 4535), (h) Mt-Nd2 (Entrez GeneID numbers 17717 or 4536), (i) Mt-Nd3 (Entrez GeneID numbers 17718 or 4537), (j) Mt-Nd4 (Entrez GeneID numbers 17719 or 4538), (k) Mt-Nd41 (Entrez GeneID numbers 17720 or 4539), (l) Mt-Nd5 (Entrez GeneID numbers 17721 or 4540), (m) Mt-Nd6 (Entrez GeneID numbers 17722 or 4541), (n) Atp5a1 (Entrez GeneID numbers 11946 or 498), (o) Atp5c1 (Entrez GeneID numbers 11949 or 509), (p) Atp5o (Entrez GeneID numbers 28080 or 539), (q) Cox5b (Entrez GeneID numbers 12859 or 1329), (r) Cox7a2 (Entrez GeneID numbers 12866 or 1347), (s) Cyc1 (Entrez GeneID numbers 66445 or 1537), (t) Hspc051 (Entrez GeneID number 66152 or 29796), (u) Ndufa5 (Entrez GeneID numbers 68202 or 4698), (v) Ndufb5 (Entrez GeneID numbers 66046 or 4711), (w) Sdhd (Entrez GeneID numbers 66925 or 6392), (x) Uqcrb (Entrez GeneID numbers 67530 or 7381), and (y) Uqcrc1 (Entrez GeneID numbers 22273 or 7384).

In some embodiments, the kit comprises primer pairs that hybridize under stringent conditions to a target sequence, which may be the entire gene or any appropriate region thereof.

In some embodiments, the kit comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 1 and a second primer comprising the nucleotide sequence of SEQ ID NO: 2; the second primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 3 and a second primer comprising the nucleotide sequence of SEQ ID NO: 4; the third primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 5 and a second primer comprising the nucleotide sequence of SEQ ID NO: 6; the fourth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 7 and a second primer comprising the nucleotide sequence of SEQ ID NO: 8; the fifth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 9 and a second primer comprising the nucleotide sequence of SEQ ID NO: 10, the sixth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 11 and a second primer comprising the nucleotide sequence of SEQ ID NO: 12, the seventh primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 13 and a second primer comprising the nucleotide sequence of SEQ ID NO: 14, the eighth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 15 and a second primer comprising the nucleotide sequence of SEQ ID NO: 16, the ninth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 17 and a second primer comprising the nucleotide sequence of SEQ ID NO: 18, the tenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 19 and a second primer comprising the nucleotide sequence of SEQ ID NO: 20, the eleventh primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 21 and a second primer comprising the nucleotide sequence of SEQ ID NO: 22, the twelfth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 23 and a second primer comprising the nucleotide sequence of SEQ ID NO: 24, the thirteenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 25 and a second primer comprising the nucleotide sequence of SEQ ID NO: 26, the fourteenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 27 and a second primer comprising the nucleotide sequence of SEQ ID NO: 28, the fifteenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 29 and a second primer comprising the nucleotide sequence of SEQ ID NO: 30, the sixteenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 31 and a second primer comprising the nucleotide sequence of SEQ ID NO: 32, the seventeenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 33 and a second primer comprising the nucleotide sequence of SEQ ID NO: 34, the eighteenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 35 and a second primer comprising the nucleotide sequence of SEQ ID NO: 36, the nineteenth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 37 and a second primer comprising the nucleotide sequence of SEQ ID NO: 38, the twentieth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 39 and a second primer comprising the nucleotide sequence of SEQ ID NO: 40, the twenty-first primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 41 and a second primer comprising the nucleotide sequence of SEQ ID NO: 42, the twenty-second primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 43 and a second primer comprising the nucleotide sequence of SEQ ID NO: 44, the twenty-third primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 45 and a second primer comprising the nucleotide sequence of SEQ ID NO: 46, the twenty-fourth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 47 and a second primer comprising the nucleotide sequence of SEQ ID NO: 48, the twenty-fifth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 49 and a second primer comprising the nucleotide sequence of SEQ ID NO: 50.

In some embodiments, the kit further comprises at least one primer pair that amplifies a gene showing little or no upregulation by PGC-1a. In some embodiments, at least one primer pair amplifies a gene selected from (a) Actb (Entrez GeneID 11461), (b) Aamp (Entrez GeneID 227290), (c) Cenpb (Entrez GeneID 12616), (d) Eefla1 (Entrez GeneID 13627), (e) Jund (Entrez GeneID 16478), (f) Lsp1 (Entrez GeneID 16985), (g) Rps2 (Entrez GeneID 16898), and (h) Rps27a (Entrez GeneID 78294). In some embodiments, the first primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 51 and a second primer comprising the nucleotide sequence of SEQ ID NO: 52; the second primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 53 and a second primer comprising the nucleotide sequence of SEQ ID NO: 54; the third primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 55 and a second primer comprising the nucleotide sequence of SEQ ID NO: 56; the fourth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 57 and a second primer comprising the nucleotide sequence of SEQ ID NO: 58; the fifth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 59 and a second primer comprising the nucleotide sequence of SEQ ID NO: 60, the sixth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 61 and a second primer comprising the nucleotide sequence of SEQ ID NO: 62, the seventh primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 63 and a second primer comprising the nucleotide sequence of SEQ ID NO: 64, the eighth primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 65 and a second primer 66.

In some embodiments, the kit further comprises at least one primer pair that amplifies a gene that is down-regulated by PGC-1α. In some embodiments, the primer pair amplifies a gene selected from (a) Cyb5r3 (Entrez Gene ID 109754), and (b) Fhl1 (Entrez Gene ID 14199). In some embodiments, the first primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 67 and a second primer comprising the nucleotide sequence of SEQ ID NO: 68; the second primer pair comprises a first primer comprising the nucleotide sequence of SEQ ID NO: 69 and a second primer comprising the nucleotide sequence of SEQ ID NO: 70. In some embodiments, the kit further comprises reagents for amplifying DNA, wherein the reagents include a DNA polymerase.

VI. Formulations

Any of the compounds employed according to the present invention may be contained in any appropriate amount in any suitable carrier substance, and is generally present in an amount of 1-95% by weight of the total weight of the composition. The composition may be provided in a dosage form that is suitable for the oral, parenteral (e.g., intravenously, intramuscularly), rectal, cutaneous, nasal, vaginal, inhalant, skin (patch), or ocular administration route. Thus, the composition may be in the form of, e.g., tablets, capsules, pills, powders, granulates, suspensions, emulsions, solutions, gels including hydrogels, pastes, ointments, creams, plasters, drenches, osmotic delivery devices, suppositories, enemas, injectables, implants, sprays, or aerosols. The pharmaceutical compositions may be formulated according to conventional pharmaceutical practice (see, e.g., Remington: The Science and Practice of Pharmacy, 20th edition, 2000, ed. A. R. Gennaro, Lippincott Williams & Wilkins, Philadelphia, and Encyclopedia of Pharmaceutical Technology, eds. J. Swarbrick and J. C. Boylan, 1988-1999, Marcel Dekker, New York).

If more than one agent is employed, each agent may be formulated in a variety of ways that are known in the art. In one embodiment, the agents are formulated together for the simultaneous or near simultaneous administration of the agents. Such co-formulated compositions can include the two agents formulated together in the same pill, capsule, liquid, etc. It is to be understood that, when referring to the formulation of such combinations, the formulation technology employed is also useful for the formulation of the individual agents of the combination, as well as other combinations of the invention. By using different formulation strategies for different agents, the pharmacokinetic profiles for each agent can be suitably matched.

The individually or separately formulated agents can be packaged together as a kit. Non-limiting examples include kits that contain, e.g., two pills, a pill and a powder, a suppository and a liquid in a vial, two topical creams, etc. The kit can include optional components that aid in the administration of the unit dose to patients, such as vials for reconstituting powder forms, syringes for injection, customized IV delivery systems, inhalers, etc. Additionally, the unit dose kit can contain instructions for preparation and administration of the compositions. The kit may be manufactured as a single use unit dose for one patient, multiple uses for a particular patient (at a constant dose or in which the individual compounds may vary in potency as therapy progresses); or the kit may contain multiple doses suitable for administration to multiple patients (“bulk packaging”). The kit components may be assembled in cartons, blister packs, bottles, tubes, and the like.

In one embodiment, the therapeutic agent is formulated with a pharmaceutically acceptable carrier. Examples of materials which can serve as pharmaceutically acceptable carriers include sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; pH buffered solutions; polyesters, polycarbonates and/or polyanhydrides; and other non-toxic compatible substances employed in pharmaceutical formulations. Wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and other antioxidants can also be present in the compositions.

The compounds may be formulated with pharmaceutically acceptable salts. The term “pharmaceutically acceptable salt” refers to salts which retain the biological effectiveness and properties of the compounds of this invention and which are not biologically or otherwise undesirable. In many cases, the compounds of this invention are capable of forming acid and/or base salts by virtue of the presence of amino and/or carboxyl groups or groups similar thereto. Pharmaceutically acceptable base addition salts can be prepared from inorganic and organic bases. Salts derived from inorganic bases, include by way of example only, sodium, potassium, lithium, ammonium, calcium and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary and tertiary amines, such as alkyl amines, dialkyl amines, trialkyl amines, substituted alkyl amines, di(substituted alkyl) amines, tri(substituted alkyl) amines, alkenyl amines, dialkenyl amines, trialkenyl amines, substituted alkenyl amines, di(substituted alkenyl) amines, tri(substituted alkenyl) amines, cycloalkyl amines, di(cycloalkyl) amines, tri(cycloalkyl) amines, substituted cycloalkyl amines, disubstituted cycloalkyl amine, trisubstituted cycloalkyl amines, cycloalkenyl amines, di(cycloalkenyl) amines, tri(cycloalkenyl) amines, substituted cycloalkenyl amines, disubstituted cycloalkenyl amine, trisubstituted cycloalkenyl amines, aryl amines, diaryl amines, triaryl amines, heteroaryl amines, diheteroaryl amines, triheteroaryl amines, heterocyclic amines, diheterocyclic amines, triheterocyclic amines, mixed di- and tri-amines where at least two of the substituents on the amine are different and are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic, and the like. Also included are amines where the two or three substituents, together with the amino nitrogen, form a heterocyclic or heteroaryl group.

VII. Administration of Compositions

The preferred amount of the compounds of the invention is a therapeutically effective amount thereof which is also medically acceptable. Actual dosage levels of in the pharmaceutical compositions of the present invention may be varied so as to obtain an amount which is effective to achieve the desired therapeutic response for a particular patient, pharmaceutical composition, and mode of administration, without being toxic to the patient. The selected dosage level and frequency of administration will depend upon a variety of factors including the route of administration, the time of administration, the duration of the treatment, other drugs, compounds and/or materials used in combination with the compounds of the invention, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. A physician having ordinary skill in the art can readily determine and prescribe the therapeutically effective amount of the pharmaceutical composition required.

Effective amounts can be determined, for example, by measuring increases in the immune response, for example, by the presence of higher titers of antibody, the presence of higher affinity antibodies, the presence of a desired population of immune cells such as memory cells to a particular antigen, or the presence of particular antigen specific cytotoxic T cells. Effective amounts also can be measured by a reduction in microbial load in the case of an infection or in the size or progression of a tumor in the case of cancer. An effective amount also may be reflected in a reduction in the symptoms experienced by a particular subject being treated.

Dosage may be adjusted appropriately to achieve desired drug levels, locally or systemically. Generally, daily doses of compounds will be from about 0.001 mg/kg per day to 1000 mg/kg per day. It is expected that doses in the range of about 0.1 to 50 mg/kg per day will be effective. In the event that the response in a subject is insufficient at such doses, even higher doses (or effective higher doses by a different, more localized delivery route) may be employed to the extent that patient tolerance permits. In one embodiment, each drug is administered one to four times daily for at least one day, at least 1-4 weeks, at least 1-11 months, or at least 1-10 years, and may even be for the life of the patient. Chronic, long-term administration will be indicated in many cases.

A variety of administration routes are available. The particular mode selected will depend of course, upon the particular drug selected, the severity of the disease state being treated and the dosage required for therapeutic efficacy. The methods of this invention, generally speaking, may be practiced using any mode of administration that is medically acceptable, meaning any mode that produces effective levels of the active compounds without causing clinically unacceptable adverse effects. Such modes of administration include oral, rectal, sublingual, topical, nasal, transdermal or parenteral routes. The term “parenteral” includes subcutaneous, intravenous, intramuscular, or infusion. Oral and intravenous routes are preferred. For administration by injection, conventional carriers well known to those of ordinary skill in the art can be used.

One preferred manner of administration for the conditions detailed above is oral, using a convenient daily dosage regimen which can be adjusted according to the degree of affliction. For such oral administration, a pharmaceutically acceptable, non-toxic composition is formed by the incorporation of any of the normally employed excipients, such as, for example, mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, sodium cross-carmellose, glucose, gelatin, sucrose, magnesium carbonate, and the like. Such compositions take the form of solutions, suspensions, tablets, dispersible tablets, pills, capsules, powders, sustained release formulations and the like.

Other delivery systems can include time-release, delayed release or sustained release delivery systems. Such systems can avoid repeated administrations of the conjugates of the invention, increasing convenience to the subject and the physician. Many types of release delivery systems are available and known to those of ordinary skill in the art. They include polymer based systems such as polytactic and polyglycolic acid, polyanhidrides and polycaprolactone; wax coatings, compressed tablets using conventional binders and excipients, and the like. Bioadhesive polymer systems to enhance delivery of a material to the intestinal epithelium are known and described in published PCT application WO 93/21906. Capsules for delivering agents to the intestinal epithelium also are described in published PCT application WO 93/19660.

A physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition of mebendazole, cytochalasin E, deoxysappanone, nocodazole, paclitaxel, podofilox, podophyllotoxin acetate or vinblastine that is required to treat the condition. For example, the physician or veterinarian could start doses of the drug and increase or decrease the levels as required in order to achieve the desired therapeutic effect. One skilled on the art may rely on dosages used to treat other conditions. The effective amount of the compound may be one sufficient to reduce, inhibit, ameliorate, or delay at least one sign or symptom of the disease or condition (e.g., cell necrosis and apoptosis or organ failure). The amount of compound administered can be dependent upon the disease to be treated, the particular compound being employed, and the pharmacokinetics and pharmacodynamics of the drug in the subject being treated.

EXEMPLIFICATION

The invention now being generally described, it will be more readily understood by reference to the following examples, which are included merely for purposes of illustration of certain aspects and embodiments of the present invention, and are not intended to limit the invention, as one skilled in the art would recognize from the teachings hereinabove and the following examples, that other DNA microarrays, cell types, agents, constructs, or data analysis methods, all without limitation, can be employed, without departing from the scope of the invention as claimed.

The contents of any patents, patent invention, patent publications, or scientific articles referenced anywhere in this invention are herein incorporated in their entirety.

Example 1

We performed gene expression-based screening for mitochondrial biogenesis and cellular assays of mitochondrial function in mouse skeletal muscle cells. Approximately ˜2500 compounds were screened.

Culture and Differentiation of Myoblasts in 384-Well Format

We have optimized protocols for growing and differentiating murine C2C12 myoblasts. These cells are simple to culture, can be differentiated into myotubes, and have been investigated in the context of mitochondrial biogenesis following electrical stimulation (Wu et al. 1999) and PGC-1α transduction (Connor et al. 2001). FIG. 1 shows myotubes in 384-well plate wells stained for nuclei with Hoechst (FIG. 1B) and for myotube morphology with anti-myosin heavy chain (FIG. 1A). The nuclei were counted using Axon ImageXpress automated imaging analysis. We detected 5313+/−384 nuclei per well, corresponding to a coefficient of variation (CV) of 7%.

Cellular Assays of Mitochondrial Biogenesis and Function

Mitochondria are complex organelles that serve as the home for oxidative phosphorylation (OXPHOS), key steps of apoptosis, ROS homeostasis, and other key cellular pathways. Owing to this complexity, multiple measurements are necessary to characterize the state of mitochondrial function. We have developed several cell-based readouts of mitochondrial function and have adapted them to 384-well format. Here, we describe each assay and its reproducibility:

Assay 1: Calcein Quantitation of Apoptosis

Mitochondria are often referred to as the gatekeepers of apoptosis (Wei et al. 2001) and we expect many compounds will induce apoptosis. Calcein stains are commercially available and provide fluorescent readouts of apoptosis. This assay is a simple add and read assay and we have adapted it to C2C12 myotubes with a CV of 8-13%. We can quantitate staurosporine-induced cell death in a dose dependent manner (FIG. 3-1).

Assay 2: MTT Assay for Cellular Dehydrogenase Activity

The cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide (MTT), is a good indicator of cell viability and proliferation, as well as mitochondrial enzyme activity. Mitochondria are a likely site a site for MTT reduction, where MTT is converted to a colored formazan byproduct via a group of mitochondrial dehydrogenases, including NADH dehydrogenase, malate dehydrogenase, and succinic dehydrogenase. We incubated cells for 2 hours in medium to which MTT was added, and measured MTT reduction as a change in absorbance at 540 nm. Measurement of MTT activity is inhibited by the complex I inhibitor rotenone (FIG. 3-2).

Assay 3: JC-1 Detection of Mitochondrial Membrane Potential

One of the mitochondrion's key bioenergetic parameters is its membrane potential (Ψ_m). We measured Ψ_musing JC-1, a lipophilic cation. JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide) is a membrane-permeable probe that binds to mitochondrial membranes within cells and fluoresces green as an individual molecule (ex. 485/em. 530), but is converted to a red fluorescent form (ex. 530/em. 585) when it is internalized in a voltage-dependent manner across the mitochondrial inner membrane, forming so-called “J-aggregates”. The ratio of red to green signal is thus an indicator of Ψ_m. As shown in FIG. 3-3, the method readily detects depolarization induced by carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, with a CV of 7-13%.

Assay 4: Fluorescent Detection of ATP

Over 90% of cellular ATP is generated by mitochondrial OXPHOS. Using a commercially available reagent called Cell-Titer Glo, we have been able to quantitate cellular ATP levels in 384-well format. This reagent allows quantitation in an “add-and-read” format; the lysis buffer is supplemented with recombinant luciferase and substrate, with cellular ATP providing the necessary energy for luminescence, which is read in 10 minutes on a plate reader. We estimated our CV to be 7-12%. (FIG. 3-4).

Assay 5. Fluorescent Detection of Reactive Oxygen Species

Mitochondria are one of the primary sources of reactive oxygen species (ROS) and are elevated during injury to the electron transport chain. ROS are of outstanding relevance to diabetes since recent work from Houstis et al. has suggested they play a causal role in the development of insulin resistance (Houstis et al. 2006). We have adapted a commercially available ROS assay called 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H₂DCFDA) to 384-well format. The dye freely enters the cell and is retained intracellularly upon cleavage by cellular esterases. Once the dye is oxidized, it is converted to green fluorescent form. FIG. 3-5 depicts the results of the assay in response to increasing doses of hydrogen peroxide. Replicate measurements indicate that our CV is 6-8%.

Assay 6. Gene Expression-Based High-Throughput Screening (GE-HTS) for Mitochondrial Biogenesis

To complement these physiological assays, we also performed gene expression-based high-throughput screening (GE-HTS) to profile transcripts associated with nuclear and mitochondrial DNA (mtDNA) expression of genes related to oxidative phosphorylation (OXPHOS). GE-HTS is a technique that uses a gene expression signature itself as the “readout” in high-throughput screening. It has already been applied to cancer gene expression for the discovery of novel lead compounds (Stegmaier et al. 2004; Hieronymus et al. 2006; Peck et al. 2006). We have developed a GE-HTS assay corresponding to the OXPHOS gene expression signature that we and others have reported in human diabetes (Mootha et al. 2003; Patti et al. 2003).

GE-HTS is a facile, high-throughput method that quantifies dozens of transcripts simultaneously. It is a multiplexed PCR strategy that combines ligation-mediated amplification with multicolored bead detection to identify and quantify transcripts of interest. We adapted GE-HTS to profile simultaneously all 13 mtDNA-encoded OXPHOS (mtOXPHOS) transcripts as well as 12 nuclear-encoded OXPHOS (nuOXPHOS) transcripts. These 12 nuOXPHOS transcripts include representatives from all five OXPHOS protein complexes and were selected because they capture virtually all of the variation in gene expression shown by the entire OXPHOS repertoire, as assessed by analysis of over 5,000 genome-wide microarrays. (Table 1) Of note, our GE-HTS assay also monitored transcripts that tend to be anticorrelated to OXPHOS expression or are invariant across many conditions as assessed by microarray assays, and thereby assist in data analysis. Together, our GE-HTS assay faithfully ‘tags’ the expression of the entire OXPHOS system. FIG. 3-6 illustrates the induction of OXPHOS genes by treatment with PGC-1a. Because the expression of OXPHOS genes is so highly correlated, measuring multiple transcripts increases the signal-to-noise ratio with which we can detect subtle effects of individual compounds.

Finally, the GE-HTS assay also provides a means to focus on the relationship between nuclear OXPHOS (nuOXPHOS) and mtDNA OXPHOS (mtOXPHOS) transcription. Chemical compounds that influence the two sets of genes in a coordinated manner can be identified, as can those which decouple the coordination between the two genomes.

To perform GE-HTS, transcripts of genes isolated from a sample are bound to poly-dT. Two nucleic acid primers to each of 13 mitochondrial-DNA-encoded OXPHOS (mtOXPHOS) transcripts and each of 12 nuclear-encoded OXPHOS (nuOXPHOS) transcripts are designed. One primer, the upstream primer, binds to the 5′ end of the target sequence. The upstream primer contains nucleotides that complement the target sequence, linked to nucleotides of a tag sequence, which are in turn linked to nucleotides that complement the universal primer (T7) site. A second primer, the downstream primer, binds to the 3′ end of the target sequence. The downstream primer contains nucleotides that complement the target sequence, linked to nucleotides that complement the universal primer (T3) site, and is phosphoryated. The SEQ ID numbers and sequences for the upstream and downstream primers used in the examples of this invention are listed in Table 10. After a pair of primers has bound to the target sequences, the pair is elongated and annealed to produce a copy of the target. The copy now contains the complement of the target sequence, the tag sequence, and both universal primer sites. An additional round of amplification is performed on the annealed copy, using a T3 primer and a T7 primer that has been biotinylated, to produce amplification products that contain the target sequence, a tag sequence, and are biotinylated. The amplification products are hybridized against a pool of colored beads, each of which has a nucleic acid that is complementary to one of the tag sequences. The amplification products are further incubated with streptavidin-phycoerythrin, which confers a fluorescent label on the biotin. The colored beads bound to the amplification products are subjected to flow cytometry, which serves to identify which tag sequences—and corresponding target genes—have been amplified. Fluorescently labeled amplification products are further quantified to determine the levels of target gene produced.

For these experiments, Applicants selected as tags nucleic acid sequences from a set of 35 (Table 9), but Applicants note that tags known in the art, or other nucleic acid sequences not present in the target sequences, could be used. In addition, the universal primers T3 and T7 were used, but any other universal primer or any other nucleic acid sequence not present in either the target sequence or the tag sequence could be used. In addition, biotin and streptavidin-phycoerythrin were used as binding moieties and phycoerythrin was used to confer a fluorescent label on the biotin. Any other binding moiety and fluorescent label known in the art could be substituted.

Assay 7. Immunofluorescent Detection of Cytochrome c Protein Content.

Cytochrome c is a water-soluble mitochondrial protein found in the inner mitochondrial membrane. Cytochrome c acts as an electron carrier in oxidative phosphorylation, and also plays a crucial role in apoptosis, through activation of caspase 9 and downstream caspases. We developed an immunofluorescence-based method for detecting cytochrome c. Data from our screen for cytochrome c protein expression was included in a compendium of all of our results from the 7 assays, although we excluded it from subsequent analyses owing to the high coefficient of variation.

Chemical Screening of 2490 Compounds and Bioactives

We have obtained a collection of 2490 compounds from the Spectrum Collection and the Prestwick Chemical Library, including ˜40% of all FDA approved drugs. We performed the viability, physiology and gene-expression assays in duplicate in differentiated C2C12 myotubes following 48-hour treatment with each of 2,490 compounds. Our chemical library consists of known bioactives, two-thirds of which are marketed drugs. Using a scoring algorithm dependent upon the distribution of mock-treated (DMSO) wells, we arrived at a normalized score for each assay in each well (Table 2). A compendium of our results includes data from our screen for cytochrome c protein expression, though we excluded it from subsequent analyses owing to the high coefficient of variation. Correlation analysis indicated that our remaining readouts (one for viability, four for OXPHOS physiology and one for OXPHOS gene expression) provide complementary information (FIG. 5).

Unlike traditional approaches for studying mitochondrial function, our improved screening method enables us to track systematically how changes in nuclear and mitochondrial OXPHOS gene expression are coupled to mitochondrial physiology over thousands of perturbations. We used this approach to explore three problems focused on mitochondrial biology, drug toxicity and the identification of novel therapeutics.

Example 2
Identification of Lead Compounds for Treating Mitochondrial Disorders

The GE-HTS assay is of particular interest to us since it is specifically assaying for the gene expression signature of human diabetes (Mootha Nat. Genet. 2003). We queried our compendium to identify compounds that might be capable of elevating OXPHOS expression while reducing ROS accumulation, as we and others have recently shown that a decline in OXPHOS gene expression and an elevation in ROS generation are associated with type 2 diabetes (Mootha Nat. Genet. 2003), neurodegeneration and aging.

We selected the top 22 compounds (˜1% of tail distribution) that promote the OXPHOS gene expression signature and re-tested these compounds in quadruplicate at four decreasing doses (10 μl, 0.1, 0.01 μM). Sixteen of 22 compounds reproduced the increase in expression signature at p<0.05 significance level (Kruskal-Wallis test, Dunn's multiple comparison post-test) at screening dose and 8 of these showed significance at multiple doses. Table 3 lists the top compounds identified in the screen.

In addition, we used two computational strategies to spotlight compounds that elevate OXPHOS expression while reducing ROS accumulation. First, we developed a simple analytical strategy to determine whether any structurally related set of compounds might boost OXPHOS expression while also suppressing ROS accumulation. This strategy involves organizing all compounds based on structural similarity and then asking whether members of a cluster had concordant scores in a given assay (Table 4). In FIG. 4a, the gray data points spotlight a single cluster of compounds, who share the chemical scaffold shown at the top. This cluster is significant for the desired activity, as measured by six separate assays. The advantage of this strategy is that individual compounds might show a subtle response not detectable in a primary screen with duplicate measurements, whereas the grouped analysis provides added statistical power.

Second, in a complementary approach, we sought to identify individual compounds that promote OXPHOS gene expression while reducing ROS levels. The advantage of this method is that it can reveal structurally unrelated compounds that individually exert large effects in the two assays of interest. We focused on the compounds that showed an elevation of OXPHOS expression and a decrease in ROS levels (bracketed in histogram in FIG. 4b). The structure of the compounds is also shown in FIG. 4b.

Notably, both analytical strategies spotlighted microtubule modulators, including both a microtubule stabilizer (paclitaxel) and several destabilizers (mebendazole, nocodazole, podophyllotoxin and vinblastine) (see Table 5), as agents that boost OXPHOS expression while suppressing ROS levels. The second strategy also yielded deoxysappanone B, a natural product found in sappan wood, whose molecular mode of action is unknown and has not been previously linked to microtubule biology (see Table 6). The other microtubule inhibitors within the compound collection (colchicine and griseofulvin) did not display the same decrease in ROS levels, but did show a modest increase in OXPHOS expression.

Next, we were interested in confirming these primary screening results and determining whether the effects on OXPHOS expression and ROS levels occur via shared or distinct mechanisms, and whether these were on-target or off-target effects of microtubule disruption. We therefore retested the microtubule modulators at a range of 20 nM to 20 μM (FIG. 6a). Treatment with either deoxysappanone B, mebendazole, nocodazole, podophyllotoxin or vinblastine increased OXPHOS expression and decreased ROS levels at the same dose of 2 μM. In contrast, paclitaxel showed effects in the two assays at 20 nM, suggesting a shared mechanism for OXPHOS expression and ROS level. Notably, at these doses, these compounds did not decrease cell viability (FIG. 6a), indicating that the decline in ROS is not simply a reflection of overt cytotoxicity. We also imaged tubulin immunofluorescence after treatment with deoxysappanone B and paclitaxel, two compounds that showed distinct potencies. For both compounds, the potency required for microtubule disruption was the same as that required to affect OXPHOS expression and ROS level (FIG. 7). To our knowledge, deoxysappanone B has not previously been linked to microtubule inhibition, but it now has been predicted to do so and the prediction validated by this study. Given that structurally and mechanistically diverse microtubule modulators increased OXPHOS gene expression, decreased cellular ROS and disrupted microtubules with equivalent potencies, it is likely that these effects are directly related to inhibition of microtubules, and not due to an off-target effect.

Because mtDNA replication and transcription are often coupled, we sought to determine whether any of these compounds promoted mtDNA replication. At the concentrations tested, several of these microtubule modulators—but not podophyllotoxin or vinblastine—increased mtDNA copy number approximately threefold (FIG. 6b).

We sought to determine the transcriptional mechanism by which microtubule inhibition might promote OXPHOS expression and mtDNA replication while suppressing ROS. We hypothesized that these changes might be occurring via PGC-1α, a transcriptional coactivator that regulates mitochondrial biogenesis in muscle and whose transcriptional program is diminished in type 2 diabetes. Consistent with this hypothesis, both mebendazole and deoxysappanone B induced the expression of Ppargc1α (which encodes PGC-1α) by approximately threefold (FIG. 6c). We have previously shown that the transcription factor ERRa serves as a key transcriptional partner of PGC-1α to drive OXPHOS expression in muscle, and that disruption of ERRa with the selective inverse agonist XCT790 suppresses PGC-1α-induced OXPHOS expression. Therefore, we tested whether XCT790 is capable of inhibiting compound-induced transcription. We observed that both mebendazole and deoxysappanone B increased the expression of a nuclear OXPHOS gene, Atp5a1, by 20%, and that this increase was completely inhibited by XCT790 (FIG. 6d), further suggesting a PGC-1α-dependent mechanism of compound activity. The mitochondrial ROS scavenger MnSOD is downstream of the same PGC-1α-ERRα pathway and we observed decreased cellular ROS levels after treatment with these small molecules. We also tested the effects of the compounds on MnSOD. A similar increase in MnSOD levels, which was suppressible by XCT790, was observed with these compounds (FIG. 6e). These results suggest that microtubule modulators both activate OXPHOS transcription and reduce cellular ROS levels in a manner dependent on PGC-1α and ERRα.

At a molecular level, we have uncovered an unexpected link between microtubule disruption and an increase in PGC-1α/ERRα-mediated OXPHOS gene expression. Although changes in mitochondrial staining and morphology have been associated with microtubule inhibitors, no studies have specifically documented their effects on OXPHOS expression and ROS levels. It is possible that interactions between the cytoskeleton and the mitochondrion are important in integrating cellular homeostasis throughout the cell cycle. As many of these microtubule modulators are used for treating cancer, our results may enhance understanding of the metabolic basis of chemotherapeutic action. Our studies also raise the possibility that manipulation of the microtubule pathway may reverse the gene-expression and ROS signatures associated with common degenerative diseases and that these may represent therapeutic targets.

Example 3
Exploring Cross-Talk Between Nuclear and Mitochondrial Genomes

We used the compendium of assay results to identify the cellular signals involved in coordinating nuclear OXPHOS (nuOXPHOS) and mtDNA OXPHOS (mtOXPHOS) transcription. Expression of OXPHOS genes from the two genomes must be tightly coupled to maintain energy homeostasis in the mitochondrion. Moreover, although OXPHOS expression can change in human diseases, it is often unclear whether the changes are primary or reactive and how these changes relate to cellular physiology. We therefore focused on the relationship between nuOXPHOS and mtOXPHOS transcripts across the chemical perturbations. As expected, the majority of compounds influence the two sets of genes in a coordinated manner (FIG. 8a). However, we identified some compounds that decouple the coordination between these two genomes (FIG. 8b and Table 7), a subset of which we confirmed with follow-up dose response curves and RT-PCR analysis (FIG. 8c). Specifically, we discovered that the eukaryotic protein synthesis inhibitors emetine, anisomycin and cycloheximide preferentially increase nuOXPHOS expression, implying that translational control might be important in coordinating the two genomes. Follow-up studies revealed that 1 μM cycloheximide elevated nuOXPHOS 1.3-fold but decreased mtOXPHOS 2.4-fold (FIG. 8c) Notably, we found that nuOXPHOS expression, but not mtOXPHOS expression, correlated strongly with cellular ATP levels (FIG. 8b) To determine whether nuOXPHOS expression drives the changes in ATP levels, or reacts to changes in ATP levels, we performed follow-up time-course analyses with 20 μM perphenazine, a compound that decreased nuOXPHOS expression. Whereas nuOXPHOS expression declined significantly (21%, t-test, P=0.004) within the first hour of treatment, cellular ATP levels remained unchanged (0.6%, t-test, P=0.84) at these early time points. At later time points, however, ATP levels dropped significantly (8 h: 11% decrease, t-test, P=1.4×10⁻⁵, 24 h: 27% decrease, t-test, P=6.3×10²²), suggesting that the decline in nuOXPHOS expression precedes and drives the decline in cellular ATP levels.

Our compendium is the first to interrogate the expression of both the nuclear genome and mtDNA. Although we show that the bulk of compounds coordinately regulate expression from both genomes, we found that eukaryotic protein synthesis inhibitors disrupt cross-talk between these two genomes. Similar to the demonstration that the calcium ionophore A-23187 can elevate nuOXPHOS while decreasing mtOXPHOS, we now have identified an array of chemical tools to investigate whether protein synthesis inhibitors also disrupt the nuclear-to-mitochondrial genome cross-talk via known pathways or through one or more novel mechanisms.

Example 4
Exploring the Mitochondrial Basis for Drug Toxicity

To probe the role of mitochondria in human drug toxicity, we focused on the statins-HMG-CoA reductase inhibitors taken by nearly 100 million patients worldwide. Statins are associated with a 0.1-0.5% incidence of myopathy, believed to be caused by ubiquinone depletion, which can block electron transport. However, clinical and epidemiological studies of the association between statins and myopathy have produced conflicting results. Of the six statins present in our screening collection, three (fluvastatin, lovastatin, simvastatin) produced strong decreases in cellular ATP levels and MTT activity (FIG. 9a). Previous studies showed that lovastatin and simvastatin reduce MTT activity and ATP levels, consistent with our high-throughput screening results. To eliminate the possibility that we uncovered two classes based merely on potency, we measured cellular ATP levels over doses ranging up to 40 μM. We observed the same segregation of effects, with atorvastatin, pravastatin and rosuvastatin showing little to no effect on cellular or mitochondrial ATP levels (FIG. 10).

To determine whether this profile might represent a signature of drug-induced myopathy, we established a centroid profile for the three mitochondria-active statins (fluvastatin, lovastatin and simvastatin) and sought to identify other clinically used drugs with a similar assay profile. The ten nearest-neighbor drugs to the centroid statin profile (FIG. 9b) were amoxapine, cyclobenzaprine, propranolol, griseofulvin, pentamidine, paclitaxel, propafenone, ethaverine, trimeprazine and amitriptyline. Notably, five of these compounds (amoxapine, propranolol, griseofulvin, pentamidine and paclitaxel) have also been associated with skeletal muscle myopathy or myalgia, a strikingly high proportion in comparison to the small fraction of all FDA-approved drugs believed to be associated with this side effect. This suggests that the drug profile might be indicative of myopathy or myalgia. Further examination of the screening data revealed that two electron transport chain inhibitors—β-dihydrorotenone (a complex I inhibitor) and antimycin A (a complex III inhibitor)—were among the 16 nearest-neighbor compounds to this assay profile, which provides mechanistic insight into this profile. Together, the data support the idea that myopathy induced by these five other drugs could be mitochondrial in origin.

Notably, one of these nearest-neighbor drugs is propranolol, a widely used antihypertensive agent. Follow-up experiments confirmed that propranolol, but not other selective β-1 blockers, decreases cellular ATP levels in a dose-dependent manner (FIG. 10). Because many patients take both a statin and a β-blocker for cardioprotection, we tested whether the two drugs might interact to cause toxicity. We thus assessed cellular ATP levels after treatment with all possible combinations of the six statins in our collection and three β-blockers (atenolol, metoprolol and propranolol), with all concentrations falling between 2.5 and 10 μM (FIG. 9c). Although neither atenolol nor metoprolol showed an effect either alone or in combination with any statin, propranolol had an additive effect on statin-induced decrease in ATP levels, as determined using the Bliss independence model (FIG. 9c). Our screening compendium and follow-up experiments (FIG. 9c) thus raise the potentially important hypothesis that patients on a combination of propranolol and one of the three statins (fluvastatin, lovastatin, simvastatin) might be at a higher risk for developing myopathy or myalgia. The additive interaction we reveal between the statins and propranolol suggests that patients taking both statins and propranolol might be at increased risk for developing skeletal muscle myopathy or myalgia. Because many patients with heart disease are likely to be on this drug combination, our hypothesis can be tested easily and may help to account for the conflicting reports on skeletal muscle myopathy associated with statins.

Example 5
Measurement of Glucose Uptake After Paclitaxel Treatment

For 3 hour paclitaxel treatment, differentiated myotubes were pre-incubated in serum-free DMEM for 1.5 hours followed by 2.5 hour treatment with 1 nM or 1 μM paclitaxel in serum-free DMEM. For 30 minute paclitaxel treatment, differentiated myotubes were pre-incubated in serum-free DMEM for 4 hours. Cells in 12 well dishes were then washed twice with KRH (140 mM NaCl, 5 mM KCl, 2.5 mM MgSO₄, 1 mM CaCl₂, 20 mM HEPES) and incubated with pre-warmed KRH (690 ul) containing 1 nM or 1 μM paclitaxel at 37° C. for 30 min. After this period, tritiated 2-deoxyglucose (2DG) and unlabeled 2DG (total vol. 50 μl) were dispensed into each well for a final concentration of 0.5 μCi/ml and 0.1 mM respectively. Cells were incubated for an additional 5 min. at 37° C. and the reaction was stopped by placing the dish immediately on ice followed by addition of ice-cold 500 μl phloretin-PBS (0.08 mg/ml) solution per well. Cells in each well were then washed twice with ice-cold phloretin-PBS (0.08 mg/ml) solution. The plate was then dried, and 740 ul of digitonin release buffer (100 mg/ml Mannitol, 1 mg/ml digitonin) was applied to each well. After 10 min. at room temperature, 670 ul from each well was counted in a scintillation counter. Results of the glucose uptake measurements are presented in Table 8.

Materials and Methods:

Cell culture. C2C12 myoblasts (ATCC) were grown in Dulbecco's Modified Eagle's Medium (DMEM, Mediatech) supplemented with 10% (vol/vol) FBS and antibiotics (100 μg/ml penicillin/streptomycin mix) in a humidified atmosphere at 37° C. with 5% CO₂. Differentiation into myotubes was induced at 80% density on day 0 by changing the medium to DMEM supplemented with 2% (vol/vol) horse serum.

Cell-based high-throughput screening. For all screening, 4,000 C2C12 myoblasts per well were seeded into either black or white 384-well optical-bottom plates (Nunc) at 50 μl per well. On day 4 of differentiation, 100 nl of each compound was pin-transferred in duplicate into fresh medium with a steel pin array, using the CyBi-Well robot (CyBio). To increase the number of mock-treated wells included in the control distribution, we added an additional plate containing DMSO alone. Compound-treated plates were incubated at 37° C. for 48 h. All cell-based assay measurements were performed using the EnVision plate reader (PerkinElmer). The coefficient of variation for each of these assays was estimated to be less than 15%. All data has been deposited in ChemBank: see the World Wide Web at chembank.broad.harvard.edu/assays/view-project.htm?id=1000453.

Calcein viability assay. Medium was aspirated from plates, and 30 μl per well 1 μM calcein-AM (Molecular Probes) in phenol red-free medium was added. Plates were incubated for 1 h at 37° C. and washed three times with 50 μl per well PBS. Fluorescence was measured at excitation and emission wavelengths (ex/em) of 485 nm/530 nm.

JC-1 mitochondrial membrane potential assay. Upon depolarization, the JC-1 dye is converted from a diffuse green form to red fluorescent J-aggregates. The ratio of red to green fluorescence serves as a readout of the mitochondrial membrane potential. Medium was aspirated from plates, and 20 μl per well 3.25 μM JC-1 (Molecular Probes) in phenol red-free medium was added. Plates were incubated for 2 h at 37° C. and washed three times with 50 μl per well PBS. Fluorescence was measured first at ex/em 530 nm/580 nm (‘red’) and then at ex/em 485 nm/530 nm (‘green’).

Assay for cellular ATP levels. 20 μl per well CellTiterGlo reagent (Promega) was added to 20 μl per well of cell culture medium. Plates were agitated for 2 min and incubated for 10 min at room temperature (22-24° C.) before luminescence was measured.

MTT assay. Medium was aspirated from plates, and 50 μl per well 0.5 mg/ml MTT in phenol red-free medium was added. Plates were incubated for 2 h at 37° C., and this was followed by aspiration of MTT solution, addition of 50 μl per well DMSO to dissolve formazan crystals, and incubation at 37° C. for 30 min. After incubation, plates were equilibrated to room temperature for an additional 20-30 min. Absorbance was measured at 540 nm.

Reactive oxygen species assay. Medium was aspirated from plates, and 20 μl per well 10 μM CM-H₂DCFDA (Molecular Probes) in phenol red-free medium was added. Plates were incubated for 1 h at 37° C. and washed three times with 50 μl per well PBS. Fluorescence was measured at ex/em 485 nm/530 nm.

Cytochrome c protein detection. Cells were fixed with 3.7% (vol/vol) formaldehyde in PBS for 30 min and then washed with TBS containing 0.1% (vol/vol) Tween-20 (TBST) and blocked with TBST+3% (wt/vol) BSA for 1 h at room temperature. Cytochrome c was detected by incubating the cells with primary antibody (Cell Signaling Technology; 1:100) overnight at 4° C., washing three times with TBST, and incubating with secondary antibody (Alexa Fluor 488-conjugated anti-mouse IgG, Invitrogen; 1:250) for 1 h at room temperature. Plates were washed three times with TBST and fluorescence measured at ex/em 485 nm/530 nm.

Gene expression-based high-throughput screening. We adapted the GE-HTS assay to monitor both nuclear and mtDNA OXPHOS transcripts. To narrow down the list of potential genes from nearly 80 nuclear OXPHOS genes, we used a list of highly co-regulated OXPHOS genes that are coordinately expressed across tissues and are downstream of the PGC-1α transcriptional coactivator. From this list, we selected genes that showed the highest signal-to-noise ratio in the microarray analysis of PGC-1α overexpression in C2C12 myotubes representing all five OXPHOS complexes. We also selected two genes that are downregulated by PGC-1α with the best signal-to-noise ratio. As controls, we selected genes that showed the lowest signal (no treatment effect) and lowest noise (biological variation) in the PGC-1α overexpression data, as well as genes previously found to be invariant from the analysis of multiple microarray datasets. We selected control genes that span a wide range of expression levels to prevent biasing for abundant transcripts. The selected OXPHOS transcripts capture the bulk of the variation exhibited by the OXPHOS transcripts represented on over 5,000 publicly available mouse microarrays on the Affymetrix platform (data not shown).

From the list of OXPHOS genes and control genes for GE-HTS, we designed primer pairs with T7 and T3 universal primer sites, 40-bp target sequence split into two 20-bp sequences for each primer, and gene-specific barcode sequence attached to the 5′ primer according to the published assay specification. We selected 40-bp gene-specific target sequences that are not alternatively spliced using oligonucleotide sequences found in the Mouse Exonic Evidence-Based Oligonucleotide Chip (MEEBO, see the World Wide Web at alizadehlab.stanford.edu/). Full primer sequences are included in Tables 1 and 10.

The GE-HTS assay was performed as previously described. Because this assay measures the final amount of PCR products rather than providing a real-time measurement of gene expression, we adjusted the parameters in the original protocol so that the abundance of PCR products were within the linear range of the assay. We removed 20 μl of medium and added 25 μl of lysis buffer per well of a 384-well plate, and used 24 PCR cycles instead of the 29 cycles described. We used 32 DMSO-treated and 32 PGC-1α adenovirus-treated wells per 384-well compound plate, with one additional control plate containing 192 DMSO-treated wells, 32 GFP adenovirus-treated wells and 160 PGC-1α adenovirus-treated wells. The PGC-1α adenovirus-treated cells serve as a positive control for increased OXPHOS gene expression, as previously reported.

Tubulin immunofluorescence. On day 4 of differentiation, C2C12 myotubes were treated with each compound for 48 h and then fixed for 5 min in ice-cold 100% methanol. Cells were washed once in 50 μl PBSTB2 (PBS with 0.1% (vol/vol) Tween-20 and 2% (wt/vol) BSA) and blocked in PBSTB2 for 1 h at room temperature or overnight at 4° C. Cells were incubated with an anti-α-tubulin (Sigma-Aldrich) antibody, 1:1,000 in PBSTB2, for 1 h at room temperature, and then washed three times with PBSTB2. Cells were incubated with secondary antibody (Alexa 488-conjugated anti-mouse antibody, 1:500 in PBSTB2) (Molecular Probes) and Hoechst 33342 for 1 h at room temperature and then washed three times in PBSTB2. Cells were visualized using an automated microscope (IX-Micro, Molecular Devices).

Quantitative PCR of mtDNA and transcripts: mtDNA quantification. Mitochondrial DNA copy number was assessed by quantifying the abundance of the mitochondrial gene mt-Co1 (encoding Cox1) relative to the nuclear geneActb (encoding β-actin). DNA from cells were extracted using DNeasy (Qiagen) and quantified for mt-Co1 and Actb copy number using quantitative PCR (Applied Biosystems). The change in the mt-Co1/Actb ratio between the compound-treated and DMSO control cells represents the fold change in mtDNA copy number.

Gene expression. We extracted RNA using an RNeasy kit (Qiagen) and synthesized cDNA using a high-capacity cDNA reverse transcription kit (Applied Biosystems) with random hexamers, as described by the manufacturer. The cDNA was then used for real-time PCR quantification of products for mouse Atp5a1 (Mm00431960_ml), Sod2 (MnSOD; Mm01313000_m1) and Ppargc1a (Mm00447183_m1), with Hprt1 (Mm03024075_m1) serving as an internal control, using TaqMan gene-expression assays (Applied Biosystems).

Statistics: cell-based screening. Composite Z-scores reflecting compound performance as compared to a mock-treated (DMSO) distribution were calculated as described. (see also the World Wide Web at chembank.broad.harvard.edu/details.htm?tag=Help#screeningData).

GE-HTS. We first eliminated wells that failed the assay reaction by filtering out wells in which the raw expression value of Rps2 (a control gene) was 2 s.d. below the median DMSO control value for each plate. We normalized for plate-to-plate variation by scaling the per-well expression level of each gene to the median expression level of that gene in PGC-1α control wells on each plate. We set the median PGC-1α-treated expression value for each gene to 1, and then normalized for well-to-well variation by dividing the expression level of each OXPHOS gene by the average value of eight control genes for each well. This number represents the processed data value.

To score the expression levels of 12 nuclear- and 13 mitochondrial-encoded OXPHOS genes, we first weighted each gene by its ability to distinguish DMSO control wells from PGC-1α-treated wells. We calculated the signal-to-noise ratio of each gene using our PGC-1α-treated positive control and DMSO negative control, and multiplied the expression value of each gene per well by this signal-to-noise ratio. We then summed these weighted scores over nuclear-encoded or mitochondrial-encoded OXPHOS genes to derive one score each for expression within each genome. Composite Z-scores were calculated as described above.

Similarity between assay profiles. We used the cell-based composite Z-scores from the ATP, MTT, JC-1 and ROS assays to calculate the root-mean-square distance between performance vectors, as this statistic gives greater weight to values far from zero. We obtained centroid statin scores by taking the arithmetic mean of the composite Z-scores from these four assays.

Identifying structurally related small molecules. We used Pipeline Pilot (Scitegic) to perform K-means clustering of the molecules based on common and biologically intuitive chemical features (molecular weight, octanol-water partition coefficient, number of hydrogen bond donors and acceptors, and number of rotatable bonds). We set K to 624 to result in an average of 5 compounds per cluster. To detect enrichment for assay performance within each compound cluster, we performed the Mann-Whitney rank-sum test on each cluster in each assay.

TABLE 1

OXPHOS genes profiled by GE-HTS and 40-base

pair target sequences used for GE-HTS probes.

Gene Name Entrez

Type
GeneID number
Upstream (5′-3′)
Downstream (5′-3′)

mtOXPHOS
Mt-Atp6
TTCAAGCCTACGTATTCACC
CTCCTACTAACCCTATATCT

17705 or 4508
SEQ ID NO: 1
SEQ ID NO: 2

mtOXPHOS
Mt-Atp8
TCACCAAAATCACTAACAAC
CATAAAAGTAAAAACCCCTT

17706 or 4509
SEQ ID NO: 3
SEQ ID NO: 4

mtOXPHOS
Mt-Co1
CACGACGCTACTCAGACTAC
CCAGATGCTTACACCACATG

17708 or 4512
SEQ ID NO: 5
SEQ ID NO: 6

mtOXPHOS
Mt-Co2
AACAAACGACCTAAAACCTG
GTGAACTACGACTGCTAGAA

17709 or 4513
SEQ ID NO: 7
SEQ ID NO: 8

mtOXPHOS
Mt-Co3
TAGGACTTTACTTCACCATC
CTCCAAGCTTCAGAATACTT

17710 or 4514
SEQ ID NO: 9
SEQ ID NO: 10

mtOXPHOS
Mt-Cytb
CTAATACCTTTCCTTCATAC
CTCAAAGCAACGAAGCCTAA

17711 or 4519
SEQ ID NO: 11
SEQ ID NO: 12

mtOXPHOS
Mt-Nd1
TACTACTATCATCAACATTC
CTATGGATCCGAGCATCTTA

17716 or 4535
SEQ ID NO: 13
SEQ ID NO: 14

mtOXPHOS
MtNd2
TTCTTCCTTACAACCCATCC
CTCACTCTACTCAACCTCAT

17717 or 4536
SEQ ID NO: 15
SEQ ID NO: 16

mtOXPHOS
Mt-Nd3
TTACATTTCTATTATTTGAC
CTAGAAATTGCTCTTCTACT

17718 or 4537
SEQ ID NO: 17
SEQ ID NO: 18

mtOXPHOS
Mt-Nd4
ACTACGAACGGATCCACAGC
CGTACTATAATCATCGCCCG

17719 or 4538
SEQ ID NO: 19
SEQ ID NO: 20

mtOXPHOS
Mt-Nd41
ATTATAACTTCAGTAACTTC
CCTAAACTCCAACTCCATAA

17720 or 4539
SEQ ID NO: 21
SEQ ID NO: 22

mtOXPHOS
Mt-Nd5
CCTACTAATTACACTAATCG
CCACTTCTATAACAGCTATG

17721 or 4540
SEQ ID NO: 23
SEQ ID NO: 24

mtOXPHOS
Mt-Nd6
GAGATTCGTTGATGTATCAG
GTTGATGATGTTGGAGTTAT

17722 or 4541
SEQ ID NO: 25
SEQ ID NO: 26

nuOXPHOS
Atp5a1
AAAGGGTTACTCTTGTATTC
CTGATGTACAGAAATCACAT

11946 or 498
SEQ ID NO: 27
SEQ ID NO: 28

nuOXPHOS
Atp5c1
CTTGACTTTCAACCGCACCC GCCAGGCTGTCATCACAAAG

11949 or 509
SEQ ID NO: 29
SEQ ID NO: 30

nuOXPHOS
Atp5o
GCTGAAGAGCTTCCTGAGTC
CAAACCAAATACTCAAACTG

28080 or 539
SEQ ID NO: 31
SEQ ID NO: 32

nuOXPHOS
Cox5b
CCAAAGGCAGCTTCACCCAC
CAAGGAAGACCCTAATCTAG

12859 or 1329
SEQ ID NO: 33
SEQ ID NO: 34

nuOXPHOS
Cox7a2
CCAATAAAGCAATCCTTAAC
CATTTTGTGTCTCCCTTTTC

12866 or 1347
SEQ ID NO: 35
SEQ ID NO: 36

nuOXPHOS
Cyc1
TTTCCCGGCCAGGCCATTCC
CATGGCTCCTCCCATCTACA

66445 or 1537
SEQ ID NO: 37
SEQ ID NO: 38

nuOXPHOS
Hspc051
TAAGGATGAGTTTCAAGTTG
CCGTTCACCGACCGCCAGTG

66152 or 29796
SEQ ID NO: 39
SEQ ID NO: 40

nuOXPHOS
Ndufa5
TCATATTCTGAAGCACTTTC
CTAAACATGCAGCCTATAGA

68202 or 4698
SEQ ID NO: 41
SEQ ID NO: 42

nuOXPHOS
Ndufb5
CTGTCCAAGAACAGTGTCTC
CCTCTAGTGGCAAGAAATGA

66046 or 4711
SEQ ID NO: 43
SEQ ID NO: 44

nuOXPHOS
Sdhd
TTTAGACAAGTTCAATTTAG
GGAGTTCTCCTTCTTTCTGG

66925 or 6392
SEQ ID NO: 45
SEQ ID NO: 46

nuOXPHOS
Uqcrb
CTGGATGGTTTTCGAAAGTG
GTATTATAATGCTGCAGGAT

67530 or 7381
SEQ ID NO: 47
SEQ ID NO: 48

nuOXPHOS
Uqcrc1
TCCCACACTACAACCGGATC
CGCACTGGCATGTTCTGGCT

22273 or 7384
SEQ ID NO: 49
SEQ ID NO: 50

Control
Actb
TAAGTGGTTACAGGAAGTCC
CTCACCCTCCCAAAAGCCAC

11461
SEQ ID NO: 51
SEQ ID NO: 52

Control
Aamp
GGGTGCGTCTTTCTATGTTG
GCGTTAGGTCTTTGAGGTTC

227290
SEQ ID NO: 53
SEQ ID NO: 54

Control
Cenpb
GTCCAGCCACCCACGTGCTC
CTTTCCCAGCTTGAATTCAA

12616
SEQ ID NO: 55
SEQ ID NO: 56

Control
Eefla1
ATAACAATGCATCGTAAAAC
CTTCAGAAGGAAAGAATGTT

13627
SEQ ID NO: 57
SEQ ID NO: 58

Control
Jund
CCGCCTCTCTACCCCCAGTC
CTGCCCGTGGCTGCCCCTTT

16478
SEQ ID NO: 59
SEQ ID NO: 60

Control
Lsp1
TGACCAACCCTCCAACTCTC
CTTCTCACCATCAGCTAAAG

16985
SEQ ID NO: 61
SEQ ID NO: 62

Control
Rps2
ACGGATCATCTTGTGAAAAC
CCACACCAGAGTCTCTGTTC

16898
SEQ ID NO: 63
SEQ ID NO: 64

Control
Rps27a
TCGTAAGCACCTGGAAGATG
CCCGGACTTTGTCTGACTAC

78294
SEQ ID NO: 65
SEQ ID NO: 66

PGC
Cyb5r3
ACTCCATGCAGTCTTGAGTG
CCCTAAGTTGTCAGCCCAAC

1α downreg.
109754
SEQ ID NO: 67
SEQ ID NO: 68

PGC-
Fh11
TTCTCTGAAACGCAGGATTG
CCTCCTTAACTGTACTCTCC

1α downreg.
14199
SEQ ID NO: 69
SEQ ID NO: 70

TABLE 2

Chemical Screening of 2490 Compounds and Bioactives

3120 compound instances, 2490 unique compounds, ND refers to lack of sufficient mRNA in well

Compound Name
Conc (μM)
Viability
ATP
MTT
ΔΨ_m
ROS
cyt c
GE-HTS
nucOX
mitoOX
ChemBank_ID
PubChem_SID

amiodarone
6.2
1.332
1.212
−0.418
−0.531
−0.119
0.079
0.040
0.158
−0.216
26
11467557

amiodarone
20
0.499
−0.282
−0.339
−0.092
0.119
0.336
−1.187
−0.895
−1.513
26
11489629

diazoxide
17.34
0.608
1.679
0.109
−0.769
−0.439
1.122
−0.115
0.050
−0.474
35
11467235

flufenamic acid
14.22
−0.666
0.487
−0.731
−0.780
1.304
0.763
−1.130
−1.270
−0.673
41
11467351

flufenamic acid
20
−0.975
−0.535
−0.390
−0.626
1.219
−0.184
0.770
0.487
1.187
41
11488605

flunarizine
9.88
0.920
1.573
−0.053
−0.212
0.803
−1.689
0.996
0.933
0.933
43
11467460

flunarizine
20
0.130
0.610
−1.669
0.243
1.721
−0.063
−0.270
−0.010
−0.740
43
11489198

glipizide
8.98
1.340
0.139
−1.320
−0.409
0.177
0.287
−0.192
−0.053
−0.480
72
11467279

glibenclamide
8.1
0.655
0.370
−0.746
−0.168
0.944
−0.277
0.624
0.444
0.885
74
11467464

glyburide
20
0.036
−0.140
−0.865
−0.667
−0.202
0.034
−0.452
−0.294
−0.648
74
11489632

loperamide
8.38
0.655
−0.924
−0.753
−0.252
−0.237
0.014
−1.005
−0.954
−0.954
80
11467292

loperamide
20
−0.495
−1.042
−2.178
−0.977
0.514
−0.157
0.035
0.085
−0.036
80
11489554

minoxidil
19.12
0.377
−0.208
−0.316
−0.108
0.557
0.324
2.205
2.377
1.374
82
11467168

minoxidil
20
0.011
0.333
−1.328
−0.209
0.599
0.224
−0.177
−0.186
−0.060
82
11488869

nicardipine
8.34
−0.025
−0.278
−0.660
−0.112
2.177
−0.164
−0.406
−0.487
−0.145
86
11467531

nicardipine
20
−0.049
−1.601
−1.826
0.396
0.528
0.154
−0.241
−0.238
−0.193
86
11489231

retinoic acid
13.32
−0.077
0.727
−1.296
0.099
−0.331
−0.866
0.807
0.763
0.727
104
11467405

tretinon
20
−0.349
−1.203
−1.643
0.517
−1.184
−0.225
−0.660
−0.694
−0.506
104
11489799

nifedipine
11.54
−0.782
−0.138
−1.933
0.698
0.731
0.434
−0.290
−0.422
−0.012
110
11467211

nifedipine
20
0.731
−0.073
−1.714
0.580
0.467
0.202
0.053
0.084
0.065
110
11488874

niflumic acid
14.18
−0.133
0.819
−1.178
−0.488
1.521
0.459
0.215
0.305
−0.015
112
11467403

niflumic acid
20
−0.997
0.006
−0.709
−0.522
1.253
0.836
−0.628
−0.814
−0.143
112
11488610

nimodipine
9.56
−1.133
0.613
0.071
0.075
0.329
0.124
−1.405
−1.473
−1.010
115
11468066

nimodipine
20
0.852
0.363
−1.205
0.105
0.608
−0.646
−1.093
−0.908
−1.258
115
11489378

nitrendipine
11.1
−0.538
0.016
−0.400
−0.513
0.085
−0.558
0.626
0.562
0.625
117
11468064

nitrendipine
20
−0.219
−0.492
−2.075
−0.565
0.233
−0.341
−0.229
−0.214
−0.215
117
11489381

5-nitro-2-phenylpropylaminobenzoic acid
20
−0.939
0.261
−0.786
−0.937
0.872
0.412
0.038
0.089
−0.075
121
11489293

3,3′-diindolylmethane
20
1.350
−0.064
−0.873
−0.513
1.667
0.644
−0.544
−0.389
−0.711
122
11489527

clofibrate
20
0.797
0.355
−0.842
0.089
0.576
0.336
0.000
0.030
−0.080
142
11489025

tetrandrine
6.42
−0.176
−1.161
−1.052
0.143
0.344
−3.953
0.454
0.464
0.345
193
11467818

tetrandrine
20
−2.453
−5.953
−4.728
−3.304
−1.379
−0.378
−0.806
−0.814
−0.676
193
11487841

tolazamide
12.84
−0.354
−1.359
−0.851
−0.617
0.262
−0.182
−0.146
−0.071
−0.266
196
11467702

tolazamide
20
1.405
0.628
−0.644
−0.095
−0.036
0.193
0.033
0.035
0.025
196
11489265

tolbutamide
14.8
−0.048
−0.401
−0.343
−0.734
1.202
−1.275
−0.382
−0.449
−0.210
198
11467338

tolbutamide
20
0.711
0.224
−1.174
1.011
−1.033
0.113
1.206
1.186
1.075
198
11489026

alprostadil
11.28
−0.155
−0.499
−0.185
−0.436
0.420
−0.260
1.028
0.889
1.101
220
11468166

propidium iodide
9.64
0.395
0.834
−0.491
−1.215
0.001
0.460
−0.233
0.355
−1.402
244
11467940

phorbol myristate acetate
20
0.649
0.248
1.936
−0.464
0.933
0.530
0.816
1.109
0.086
290
11489727

anisomycin
20
−3.560
−1.993
−4.207
−0.220
−2.145
−2.269
1.482
2.276
−0.371
336
11488448

aminopyridine
20
−0.911
0.747
−1.395
−0.568
0.860
0.235
−0.074
0.082
−0.380
338
11489229

piroxicam
12.08
0.909
−0.108
−1.336
−0.791
0.629
0.348
−0.643
−0.715
−0.429
347
11467359

piroxicam
20
−0.690
1.203
−0.477
−0.457
0.602
0.154
−0.280
−0.357
−0.079
347
11489103

terazosin
10.32
−0.367
−0.241
−0.654
−0.753
0.330
−0.258
−0.111
−0.106
−0.115
349
11467899

prazosin
10.44
−0.278
−0.086
−0.811
0.111
0.999
0.767
−0.027
−0.202
0.322
349
11468095

prazosin
20
0.400
0.937
−0.518
0.465
0.443
−0.394
−0.014
0.021
−0.084
349
11489105

propranolol
15.42
0.518
0.232
−0.027
0.082
0.251
1.155
1.437
1.181
1.677
351
11468100

propranolol
20
0.359
0.830
−0.670
−0.344
0.547
−1.186
−0.434
−0.473
−0.270
351
11489117

propranolol
20
−0.524
−2.413
−1.919
0.120
−0.597
0.401
0.862
0.874
0.708
351
11489515

quercetin
13.24
0.816
0.716
−1.595
−1.691
0.374
−0.214
−0.340
−0.086
−0.785
353
11467655

quercetin
20
0.686
0.361
−0.928
−1.240
0.615
0.377
0.140
−0.102
0.546
353
11487875

diltiazem
9.64
−0.495
0.024
−2.102
−1.238
0.103
−0.201
−1.187
−1.266
−0.849
355
11467282

flecainide
9.66
−0.112
1.210
−1.170
−1.026
0.987
0.763
−0.167
0.006
−0.486
359
11467883

apigenin
14.8
−0.523
−0.268
−1.068
−1.417
0.883
−1.047
−0.396
−0.501
−0.117
360
11467562

naringenin
14.7
0.350
0.892
−0.475
−0.620
0.735
1.489
0.085
0.046
0.159
360
11467614

apigenin
20
0.387
1.876
−0.297
−1.203
1.595
−0.380
0.485
0.396
0.612
360
11488244

lidocaine
17.06
−1.121
0.033
−0.512
−0.982
0.948
0.357
−0.087
−0.302
0.323
362
11467198

lidocaine
20
−0.795
0.646
−0.546
−0.204
−0.007
0.074
−0.274
−0.371
−0.016
362
11489159

statil
20
−0.878
0.377
−1.350
−0.494
0.409
−0.105
−0.398
−0.272
−0.576
366
11489283

tamoxifen
10.76
0.732
−0.361
0.087
−0.378
0.428
0.293
0.383
0.170
0.702
368
11467294

tamoxifen
20
0.201
0.489
−0.180
0.462
0.951
−0.227
−0.628
−0.461
−0.869
368
11488705

thalidomide
15.5
−0.577
1.142
−1.400
−0.697
0.788
−0.213
−1.574
−1.692
−1.073
370
11467340

thalidomide
20
−1.042
0.264
−0.660
−0.645
0.263
0.020
−0.520
−0.608
−0.249
370
11488523

N-aminohexyl-5-chloro-1-
20
−1.182
−0.809
−1.143
0.009
0.879
−0.695
−0.390
−0.463
−0.157
382
11489385

napthalenesulfonamide

camptothecin
11.48
−1.842
−1.251
−3.190
1.630
−0.859
−0.840
−0.365
−0.580
0.103
383
11467348

camptothecin
20
−2.098
−0.243
−2.979
1.140
−1.628
−2.069
−1.184
−1.166
−1.027
383
11488719

estradiol-17 beta
14.68
0.327
−0.194
0.103
−0.308
−0.074
0.327
0.056
−0.032
0.221
386
11467589

riluzole
17.08
1.079
1.652
−1.861
−0.392
0.476
−0.694
0.523
0.648
0.127
399
11467315

riluzole
20
0.036
−0.088
−1.114
0.041
0.461
1.599
0.506
0.430
0.607
399
11488366

aristolochic acid
20
−0.635
0.691
−1.200
−0.216
0.460
0.053
−0.519
−0.268
−0.943
401
11488638

bumetanide
10.98
−0.653
0.214
−1.517
−0.822
0.659
0.074
−0.294
−0.142
−0.557
404
11467424

bumetanide
20
−0.231
1.035
−0.217
1.098
1.190
0.148
0.205
0.245
0.153
404
11488866

clozapine
12.24
1.080
−0.716
0.190
−0.197
0.948
−0.153
0.781
0.861
0.463
417
11467498

clozapine
20
−0.701
0.585
−0.595
−0.309
0.824
0.242
0.523
0.744
−0.046
417
11488735

adenosine
20
−0.902
0.787
−1.853
−0.736
1.310
−0.339
−1.258
−1.131
−1.202
418
11489073

3-methyl-1-phenyl-2-pyrazolin-5-one
20
−0.103
0.165
−1.969
−1.040
0.249
0.353
−0.331
−0.202
−0.528
419
11489390

juglone
20
−1.067
−0.610
−1.295
−1.636
1.141
0.266
0.050
0.116
−0.102
422
11488594

genistein
20
−0.013
0.514
−0.560
−0.400
0.761
0.295
0.211
0.129
0.389
425
11488454

serotonin
22.7
1.124
1.590
−0.263
−0.305
−1.319
1.163
−1.359
−0.945
−1.934
429
11467629

hydroxyurea
20
0.084
−0.221
−0.728
−0.952
0.158
0.147
−0.895
−1.022
−0.523
430
11487880

3-isobutyl-1-methylxanthine
20
−0.534
0.030
−1.643
−0.967
0.472
−0.063
0.176
0.125
0.288
435
11489521

chlorpromazine
12.54
−0.895
−1.056
−1.081
−0.711
0.894
−0.093
−0.308
−0.273
−0.370
436
11467212

chlorpromazine
20
−0.936
−0.174
−1.529
−1.057
0.542
−0.615
0.070
−0.022
0.308
436
11488972

trifluoperazine
9.82
−0.169
0.516
−0.246
0.745
−0.087
−0.965
−0.760
−0.656
−0.825
437
11467461

trifluoperazine
20
0.645
0.525
−0.537
1.071
1.056
0.186
−0.557
−0.825
0.074
437
11488644

nocodazole
13.28
−0.069
−0.969
−0.751
0.358
−1.099
−2.032
1.312
1.429
0.763
440
11467248

3-aminobenzamide
20
−0.783
0.672
−0.977
−0.836
1.118
0.211
−0.293
−0.261
−0.299
445
11489393

capsaicin
13.1
−0.028
−0.974
−0.454
−0.045
0.809
0.064
−0.724
−0.737
−0.543
446
11468027

E-capsaicin
20
−0.622
0.472
−0.633
−0.489
1.016
0.316
0.497
0.422
0.523
446
11488586

clonidine
17.38
−0.791
2.923
−0.250
−0.056
0.584
0.018
0.188
0.256
0.018
448
11467396

clonidine
20
−0.836
0.357
−0.503
−0.557
0.855
1.038
−0.315
−0.218
−0.364
448
11489003

menadione
23.24
−5.459
−8.388
−6.085
−3.741
−3.391
−5.555
−1.702
−3.398
2.126
449
11467607

menadione
20
−5.205
−8.345
−6.037
−3.654
−3.319
−5.638
−3.620
−4.120
−1.870
449
11489010

corynanthine
11.28
−0.187
0.393
−1.425
−1.048
0.909
0.842
0.320
0.300
0.280
450
11467726

caffeine
20
−0.404
−0.397
−0.358
−0.718
0.914
0.292
−0.120
0.084
−0.451
451
11489077

methotrexate
8.8
−0.299
0.543
−1.961
−0.905
0.231
−0.098
−0.928
−1.019
−0.608
464
11467283

methotrexate
20
−1.003
1.034
−2.307
−1.098
0.599
−0.453
0.749
0.780
0.616
464
11488893

histamine
20
−0.723
−0.369
−1.327
−0.900
0.225
0.016
0.399
0.518
0.074
465
11488481

phenylbutyric acid
20
−1.328
0.127
−0.797
0.217
0.153
−0.651
−0.799
−0.643
−0.913
470
11489614

valproate
20
−0.340
0.535
−0.680
−0.784
0.809
0.530
0.517
0.657
0.117
471
11488762

daidzein
20
−0.071
−0.900
−1.113
−0.893
0.224
0.361
−0.561
−0.558
−0.507
592
11487869

ellagic acid
20
−0.435
0.994
−1.503
−2.499
0.347
0.534
−0.651
−0.623
−0.605
598
11488721

emodin
20
0.003
−0.079
−1.274
−3.895
1.558
0.021
−0.763
−0.781
−0.592
599
11488711

phloretin
20
0.520
0.713
−0.645
−1.675
0.245
0.383
−0.559
−0.541
−0.500
647
11488497

purpurogallin
20
0.034
1.972
−1.771
−1.670
−0.374
0.635
−0.482
−0.534
−0.237
653
11488398

baclofen
18.72
−0.598
0.492
−0.615
−0.413
0.411
0.247
−0.427
−0.363
−0.517
678
11467233

baclofen
20
0.433
0.099
−0.221
−0.022
0.824
1.066
−0.272
−0.435
0.055
678
11487908

acetarsol
20
0.084
−0.893
−1.621
−0.436
0.582
0.117
−0.156
−0.262
0.036
679
11487920

promethazine
14.06
0.035
1.538
0.239
0.684
0.803
−0.991
0.327
0.225
0.475
681
11468036

promethazine
20
−0.409
−0.487
−0.777
0.115
−0.006
0.128
−0.894
−0.905
−0.712
681
11488656

cortisone
20
0.351
0.230
−1.039
−0.669
0.568
−0.256
−0.564
−0.594
−0.318
682
11488952

metronidazole
23.38
0.496
1.379
−1.048
−0.070
−0.940
0.700
0.888
1.173
0.084
683
11467229

metronidazole
20
1.069
2.214
−0.592
0.062
−0.176
0.529
−0.512
−0.512
−0.427
683
11488699

erythromycin estolate
20
−0.315
0.361
−0.837
−0.707
0.889
0.022
−0.138
−0.261
0.144
684
11489251

kinetin
20
0.213
1.796
−0.520
0.906
0.764
0.013
−0.124
−0.047
−0.250
686
11489180

reserpine
6.58
0.678
0.494
−0.706
−0.616
1.962
0.257
0.355
0.230
0.549
687
11468023

cefazolin
8.8
0.064
0.611
−1.945
−0.676
1.124
−0.902
−1.152
−1.260
−0.711
689
11467884

cefazolin
20
0.362
0.428
−1.291
−0.045
0.543
0.674
0.036
0.110
−0.043
689
11488956

alprenolol
16.04
0.933
1.466
0.118
0.360
0.664
0.748
0.137
0.236
−0.107
690
11467398

alprenolol
20
0.025
0.158
−1.125
−0.727
0.473
−0.043
−1.425
−1.198
−1.561
690
11489630

azlocillin
8.66
0.709
0.830
−1.241
−0.741
1.825
0.178
−0.349
−0.030
−0.927
691
11467969

azlocillin
20
1.605
1.488
−0.900
0.242
−0.785
1.060
−1.102
−1.013
−1.072
691
11489338

acetazolamide
18
−0.481
3.862
−0.192
0.513
0.338
0.698
−0.621
−0.495
−0.801
692
11467151

acetazolamide
20
−0.196
−0.106
−0.676
1.204
−0.322
0.613
0.025
−0.283
0.588
692
11487898

tilorone
20
−3.332
−3.413
0.202
0.082
−1.170
−1.071
−0.585
−0.515
−0.574
693
11489558

fluorometholone
20
−1.056
0.060
−1.367
−0.308
0.548
−0.466
0.146
0.294
−0.097
694
11489082

semustine
20
−0.152
0.546
−1.124
−0.874
0.493
0.374
−1.153
−0.849
−1.568
695
11488727

anthralin
20
0.064
−1.114
−1.260
−2.161
0.943
0.348
−0.848
−0.627
−1.187
696
11487927

diprophylline
15.74
−0.984
−0.329
−1.657
−0.686
1.868
0.118
−0.188
−0.208
−0.160
697
11467181

dyphylline
20
0.622
0.530
0.201
1.225
0.735
0.010
0.844
0.615
1.085
697
11487906

fenbufen
15.74
−0.558
−0.004
−1.609
−0.707
0.460
0.051
0.578
0.553
0.481
699
11467366

fenbufen
20
−0.148
−0.649
−0.708
−0.574
0.895
−0.284
0.001
−0.028
0.059
699
11489205

homatropine
20
−0.393
0.315
−0.970
−0.642
0.643
−0.164
−1.198
−0.968
−1.364
700
11488795

ambroxol
10.58
−0.619
0.728
−0.752
−1.193
2.504
−0.108
0.145
0.128
0.151
701
11467514

ambroxol
20
1.395
0.085
0.917
0.349
0.584
−0.149
−0.060
−0.041
−0.086
701
11489334

hydroxyprogesterone
20
−0.409
−1.768
−0.554
1.288
−1.178
−2.065
0.042
0.308
−0.466
702
11488346

salicin
20
−1.626
−0.052
−2.227
−0.766
1.012
0.336
0.676
0.712
0.461
703
11488572

gentian violet
20
−3.137
−5.276
−5.314
−3.944
−2.488
−3.653
−2.735
−1.196
−5.260
704
11488904

benfluorex
11.38
−0.271
0.873
−0.780
−0.807
2.384
0.309
−1.547
−1.082
−2.217
705
11467515

benfluorex
20
0.509
0.548
−1.221
−0.621
0.943
−0.162
−0.641
−0.466
−0.790
705
11489033

sulfaquinoxaline
13.32
0.879
0.512
−0.938
−0.564
−0.447
−0.233
−0.502
−0.435
−0.553
706
11467879

sulfaquinoxaline
20
−0.211
0.118
−1.764
−0.469
0.698
0.649
−0.182
−0.272
0.104
706
11488802

digitoxin
20
−0.052
0.694
−1.108
0.910
0.919
−0.679
−0.125
−0.362
0.313
707
11487886

astemizole
8.72
−3.664
−4.284
−5.349
−0.384
−1.650
−4.866
0.336
0.208
0.494
709
11467284

astemizole
20
−5.634
−8.294
−6.684
−4.127
−3.597
−3.496
−3.310
−3.860
−1.480
709
11489548

cephalosporin C
20
−1.140
0.930
−2.039
−0.512
−0.483
0.357
−0.894
−0.988
−0.484
710
11488331

resorcinol
20
−0.117
−0.372
−0.009
−0.154
1.313
−0.863
−0.102
−0.004
−0.276
711
11489126

cephapirin
9.44
−0.570
−0.536
−2.017
−0.864
0.544
−0.120
−0.168
−0.135
−0.202
712
11467999

cephapirin
20
−0.201
−0.089
−1.765
−0.933
0.767
0.445
0.471
0.365
0.541
712
11487919

mebeverine
9.32
−1.262
−0.521
−0.344
0.316
1.404
−0.073
0.173
0.048
0.393
714
11467458

mebeverine
20
−1.152
0.368
−1.358
−0.783
0.761
−1.401
−0.917
−0.749
−1.071
714
11489220

khellin
15.38
−0.206
−0.004
−1.317
−0.176
−0.017
−0.002
−0.889
−0.890
−0.748
715
11467239

khellin
20
−0.967
0.407
−2.053
−0.473
1.119
0.584
−1.451
−1.491
−1.058
715
11488409

cyclobenzaprine
14.52
−0.881
−0.183
−1.981
−0.736
0.031
−2.311
−1.238
−1.087
−1.303
716
11467593

cyclobenzaprine
20
−1.284
−3.850
−3.640
−0.570
−2.292
−0.625
−0.371
−0.554
0.075
716
11489350

fosfosal
18.34
0.253
0.528
−1.655
−0.997
1.703
0.254
−0.831
−0.750
−0.842
717
11467963

fosfosal
20
−0.460
1.564
−1.240
−0.757
0.469
0.647
−0.488
−0.394
−0.585
717
11489274

etofylline
17.84
0.254
1.247
−1.301
−0.616
0.320
−0.750
0.681
0.706
0.438
718
11467320

7-hydroxyethyltheophylline
20
−0.541
−0.071
−0.478
−0.294
0.055
0.496
0.285
0.311
0.205
718
11489635

pargyline
25.12
−0.056
0.850
−1.666
−0.243
1.283
−0.646
−0.600
−0.523
−0.689
719
11467331

pargyline
20
−0.007
0.058
−0.197
−0.450
1.772
0.252
0.282
0.238
0.386
719
11488855

fluorouracil
20
0.778
1.481
−1.998
−0.089
0.169
−0.531
1.643
1.502
1.554
720
11487892

oleandomycin
20
−0.560
0.560
−0.960
−0.735
0.410
−0.672
−0.480
−0.571
−0.203
721
11488663

probenecid
14.02
0.196
−0.134
−1.052
−0.526
0.706
0.495
−0.414
−0.312
−0.534
722
11467690

probenecid
20
−1.102
0.967
−1.257
−1.339
−0.269
0.059
−0.937
−0.928
−0.787
722
11489110

atenolol
20
0.708
1.023
−0.547
−0.798
0.508
0.403
−0.609
−0.304
−1.106
723
11489227

nalidixic acid
17.22
−0.474
0.071
−1.669
−0.686
0.845
−0.710
0.547
0.728
0.034
724
11467335

nalidixic acid
20
−0.157
0.957
0.019
0.278
1.064
0.412
0.797
0.692
0.861
724
11489176

perillic acid
20
−1.102
0.038
−1.117
−0.470
0.937
0.117
−0.366
−0.329
−0.376
725
11488744

urethane
20
−0.741
0.192
−0.621
0.019
1.356
0.472
0.359
0.370
0.242
726
11488725

ethopropazine
12.8
−1.343
−0.482
−0.890
−0.143
0.153
0.284
−0.757
−0.332
−1.452
727
11467988

ethopropazine
20
−1.421
0.713
−0.393
−0.956
−0.292
0.259
−0.392
−0.269
−0.493
727
11488800

minaprine
13.4
−1.866
0.148
−1.670
−1.010
1.093
−0.119
0.087
0.170
−0.138
728
11467214

minaprine
20
−0.227
0.186
−2.047
−1.072
1.120
0.920
−0.719
−0.790
−0.438
728
11489223

lactulose
20
−0.225
0.319
−0.725
−0.022
0.900
−0.806
−0.650
−0.903
0.097
729
11488975

thioridazine
10.8
−1.056
0.008
−1.004
−0.460
1.385
−1.505
0.513
0.164
1.081
731
11467226

thioridazine
20
−0.071
−0.362
−1.520
−0.366
−1.412
−0.143
−0.717
−0.462
−1.098
731
11489148

3,5-dinitrocatechol
20
−0.814
−0.504
−1.388
−0.705
1.411
0.671
−0.293
−0.357
−0.020
732
11488925

memantine
22.3
0.886
0.276
0.208
0.236
0.881
−0.342
−0.672
−0.724
−0.446
733
11468126

memantine
20
−0.548
0.065
−1.104
−0.663
1.706
0.243
−0.312
0.128
−1.117
733
11489224

metoclopramide
13.34
−1.023
−0.701
−1.155
−0.701
1.422
0.037
−0.296
−0.541
0.222
734
11467357

metoclopramide
20
−0.332
0.721
−0.457
0.047
1.034
0.000
−0.588
−0.784
−0.039
734
11489536

isoniazid
29.16
1.107
1.676
−0.222
0.320
−0.562
0.260
−1.181
−1.256
−0.836
735
11467309

isoniazid
20
−0.513
−0.061
−1.832
−0.697
0.957
1.056
0.418
0.499
0.120
735
11487923

mecysteine
20
−0.261
0.371
−1.306
−0.509
0.833
0.502
0.036
0.092
−0.134
736
11487830

tiabendazole
19.88
−0.786
−0.171
−1.873
−1.093
0.578
0.746
−0.840
−0.902
−0.549
737
11467672

thiabendazole
20
0.175
−0.132
−0.902
−0.592
−0.278
−0.449
−0.525
−0.413
−0.665
737
11489147

acetanilide
20
−1.150
0.621
−1.213
−1.104
1.145
0.532
0.043
0.206
−0.295
738
11489250

glutathione
20
−0.137
0.643
−0.267
−0.067
0.732
−0.913
0.406
0.459
0.215
740
11489316

mephenesin
21.96
−0.082
0.246
−0.134
−0.680
1.161
−0.031
0.222
0.394
−0.219
741
11467326

mephenesin
20
−1.140
−0.555
−1.677
−0.506
0.945
0.922
0.154
0.349
−0.273
741
11489234

fusidic acid
20
−0.547
0.538
−1.074
−1.339
0.932
0.256
0.206
0.355
−0.066
742
11489083

terbutaline
17.76
−0.275
0.292
−0.796
−0.919
1.006
−0.434
−0.369
−0.276
−0.496
743
11467539

terbutaline
20
−0.410
0.371
−1.064
−1.297
0.995
0.201
0.431
0.402
0.407
743
11489143

paraxanthine
20
−0.737
0.570
−1.990
−0.216
0.456
−0.027
−0.685
−0.604
−0.680
744
11489549

deferoxamine
7.14
0.141
1.051
−1.645
−0.392
−0.336
0.082
0.199
0.487
−0.434
745
11467873

deferoxamine
20
−1.272
0.653
−2.241
−0.456
0.098
1.697
−0.915
−0.825
−0.848
745
11488971

antazoline
15.08
0.036
0.531
−1.337
−1.331
1.711
−0.218
0.470
0.430
0.480
746
11467406

antazoline
20
−0.129
0.474
−0.981
−0.920
0.992
0.721
−0.264
−0.238
−0.188
746
11489075

norfloxacin
12.52
0.040
−0.597
−1.145
−0.604
1.115
−0.150
−0.594
−0.507
−0.691
747
11467369

norfloxacin
20
−0.669
0.116
−1.055
−0.901
0.285
−0.477
−0.259
−0.300
−0.047
747
11488833

urea
20
0.812
0.263
0.234
0.286
−0.938
0.081
0.652
0.647
0.604
749
11489008

streptomycin
20
−1.244
0.584
−1.969
−1.109
1.559
−0.113
0.548
0.440
0.707
750
11488263

sulfadimethoxine
12.88
1.489
0.715
0.009
−0.727
−0.656
0.332
0.076
0.171
−0.135
751
11467876

sulfadimethoxine
20
−0.799
−0.336
−0.514
−0.452
0.599
0.735
−0.606
−0.713
−0.267
751
11489235

flumequine
15.32
−1.610
−0.507
−1.735
−0.579
0.909
−0.675
−0.652
−0.927
−0.009
752
11467352

flumequine
20
−0.500
0.141
0.487
0.220
−0.232
−0.301
−0.020
0.033
−0.064
752
11489016

sulfinpyrazone
9.88
−1.107
0.358
−0.836
−0.131
1.006
0.173
0.125
0.071
0.214
753
11467438

sulfinpyrazone
20
−1.098
−0.276
−0.970
−1.021
0.255
−0.838
−0.269
−0.253
−0.249
753
11489140

trimipramine
13.58
1.504
1.329
−1.526
−0.697
0.811
−3.317
−0.380
−0.309
−0.459
755
11467954

trimipramine
20
−1.573
−6.070
−4.012
2.895
−1.136
0.200
−0.909
−1.153
−0.246
755
11489346

hexylresorcinol
20
−0.106
0.408
−0.510
−0.732
0.175
−0.245
0.194
0.077
0.483
756
11488805

ciprofloxacin
12.08
−0.988
0.321
−1.677
−0.935
0.368
−0.078
−1.391
−1.441
−1.060
757
11467261

ciprofloxacin
20
−1.222
−0.033
−1.635
−0.738
0.564
0.186
−0.635
−0.648
−0.483
757
11489383

oxibendazole
20
−1.899
−0.104
−3.046
−0.975
−1.178
−1.471
0.274
0.144
0.483
758
11489372

cephalothin
10.08
0.099
−0.628
−1.062
−0.504
1.329
0.328
0.171
0.032
0.424
759
11467867

cephalothin
20
0.824
−0.562
−0.695
−0.718
0.189
0.343
0.110
0.191
−0.137
759
11487937

(S)-(−)-cycloserine
39.18
−0.457
−0.139
0.269
1.036
−0.520
0.563
−0.556
−0.736
−0.095
760
11468237

cycloserine
20
−0.112
0.623
−1.390
0.467
0.696
−0.776
0.847
0.863
0.605
760
11487900

methicillin
20
−0.246
0.669
−0.759
−0.497
0.706
−0.111
−0.080
0.024
−0.309
762
11489781

quinacrine
10
−0.579
0.313
−1.080
−1.194
2.788
−3.708
1.007
0.703
1.432
763
11467466

quinacrine
20
−6.002
−8.309
−1.910
0.428
0.865
−0.684
−2.890
−2.650
−2.810
763
11488704

droperidol
10.54
−0.013
−0.602
−0.645
0.107
1.371
0.270
0.469
0.438
0.440
764
11467508

droperidol
20
−0.670
−0.627
−1.157
−0.131
0.927
0.161
0.524
0.622
0.222
764
11489202

ethisterone
20
0.086
0.439
−1.214
−1.355
0.240
−0.080
0.590
−0.570
−0.500
766
11489353

amygdalin
20
−0.928
0.720
−1.739
−0.290
1.161
0.613
−0.243
0.013
−0.747
767
11488720

choline
20
−0.669
0.740
−0.905
−0.897
0.684
0.713
−1.448
−1.141
−1.813
768
11489754

bufexamac
17.92
−0.223
2.320
−0.617
−0.527
−0.303
0.419
−0.801
−0.599
−1.057
769
11467391

bufexamac
20
0.105
1.620
−0.950
−0.498
0.105
0.851
0.143
0.331
−0.273
769
11489273

nylidrin
20
−0.879
1.387
0.167
−0.231
0.507
0.498
−0.030
−0.010
−0.060
770
11488783

ketotifen
12.92
0.306
−0.077
−1.173
−1.085
0.844
−0.546
−0.548
−0.423
−0.679
771
11467519

ketotifen
20
−0.013
0.332
0.415
−0.358
0.491
0.292
0.569
0.377
0.908
771
11489014

piperidolate
12.36
−0.159
0.376
−0.541
−0.313
0.060
−0.186
−0.419
−0.421
−0.343
772
11468203

piperidolate
20
−0.575
−0.957
−1.693
−0.688
0.734
0.436
−0.438
−0.310
−0.543
772
11488889

econazole
10.48
0.273
−0.830
−1.573
−0.237
0.970
−0.215
0.196
0.102
0.356
773
11467452

econazole
20
0.137
−1.886
−1.114
0.948
1.668
0.068
0.496
0.341
0.725
773
11489255

aminohydroxybutyric acid
20
0.634
0.467
−0.889
−0.073
0.067
0.084
−0.127
−0.072
−0.138
775
11488945

hydralazine
24.98
0.572
0.791
−0.465
−0.591
0.325
0.204
0.181
0.315
−0.168
776
11467317

hydralazine
20
0.882
0.692
−0.830
0.069
0.162
0.687
−0.497
−0.379
−0.579
776
11488785

naringenin
20
−1.071
1.514
−0.626
0.510
0.248
1.008
−0.538
−0.248
−0.986
777
11488141

iodoquinol
20
0.242
−0.055
−0.120
2.621
−0.493
0.912
0.116
0.033
0.331
778
11488857

procaine
16.92
0.539
−0.246
−1.237
−0.685
0.875
0.260
0.441
0.516
0.150
779
11467189

procaine
20
−0.848
0.642
−0.685
−0.169
0.116
0.215
−0.322
−0.407
−0.090
779
11489112

iproniazid
22.32
−0.416
0.691
−0.696
−0.958
0.753
0.472
0.206
0.355
−0.179
780
11467324

iproniazid
20
−1.496
0.708
−0.643
−0.831
1.440
0.597
0.755
0.484
1.212
780
11488284

flunisolide
20
−0.717
0.018
0.186
0.076
0.363
−0.257
−0.472
−0.790
0.272
782
11489256

nicergoline
8.26
−0.633
0.977
−1.186
−0.869
0.630
−0.858
−0.438
−0.438
−0.385
783
11467295

nicergoline
20
−0.876
0.405
−1.563
−0.832
0.491
−0.486
−0.498
−0.405
−0.582
783
11489230

5-azacytidine
20
−2.288
0.499
−1.818
−1.175
0.540
−0.923
0.484
0.340
0.678
784
11488602

pirenzepine
11.38
−0.696
−0.699
−0.776
−0.242
0.363
−0.017
−2.019
−2.150
−1.402
786
11467277

pirenzepine
20
−1.170
0.649
−0.875
−0.784
1.438
−0.596
−0.188
−0.029
−0.476
786
11489233

homatropine
20
−0.068
1.047
−0.917
−0.524
0.072
0.399
−0.397
−0.320
−0.425
789
11488360

1r,9s-hydrastine
20
−0.738
0.964
−1.927
−0.956
0.256
0.103
−0.069
0.047
−0.209
790
11488812

quinine
20
0.079
0.789
−0.450
0.156
0.836
−1.375
−0.473
−0.528
−0.260
792
11489124

amrinone
21.36
−0.418
−0.009
0.106
−0.180
0.107
−0.100
−0.124
−0.147
−0.028
794
11467948

amrinone
20
−0.109
0.092
−0.071
−0.557
0.982
−0.579
−0.286
−0.409
−0.016
794
11489796

spectinomycin
12.04
0.964
0.661
−1.288
−0.344
0.096
0.125
−0.503
−0.293
−0.829
795
11467952

spectinomycin
20
−1.189
1.254
−1.506
−0.674
0.083
1.197
−0.353
−0.397
−0.195
795
11489131

gemfibrozil
15.98
−0.530
0.316
−1.293
−0.383
0.448
0.459
−0.917
−0.816
−0.984
796
11467362

gemfibrozil
20
−0.985
0.063
−1.395
−0.658
0.661
0.164
−0.225
−0.284
0.008
796
11488913

monensin
20
−0.176
−3.394
−2.104
3.603
−2.989
−1.704
−0.983
0.293
−3.366
797
11489325

exalamide
20
−0.103
−0.629
−0.465
−0.028
0.385
−0.362
−0.229
−0.152
−0.369
798
11488685

sulfamethizole
14.8
−0.521
0.497
−1.733
−0.450
0.468
0.322
−0.326
−0.154
−0.628
799
11467890

sulfamethizole
20
−0.244
0.866
−0.483
−0.745
0.025
0.644
0.062
0.096
−0.029
799
11489138

methyldopa
18.94
0.286
0.504
−1.421
−1.719
0.203
−1.204
0.836
0.962
0.404
800
11467474

methyldopa
20
−0.286
1.115
−0.784
−0.842
−0.145
0.755
−0.020
−0.084
0.203
800
11488884

chlorprothixene
20
−0.476
0.273
−0.824
−0.650
0.495
−0.305
−0.605
−0.636
−0.439
801
11488673

quinalizarin
20
0.583
1.276
−0.668
−2.511
0.674
0.935
−0.559
−0.517
−0.543
802
11489178

ethionamide
24.06
−1.076
−0.800
−1.292
−1.055
1.108
0.211
−0.465
−0.236
−0.839
803
11467674

ethionamide
20
−1.333
−0.464
−1.757
−0.677
0.067
−0.472
−0.192
−0.112
−0.241
803
11488810

mycophenolic acid
12.48
0.030
−1.446
−1.697
0.026
−0.251
0.220
0.100
0.062
0.155
804
11467704

mycophenolic acid
20
−0.335
−1.173
−1.793
0.210
−0.854
−0.263
−0.215
−0.297
−0.019
804
11488708

etodolac
13.92
−0.733
−0.841
−0.715
0.319
0.379
0.172
−0.440
−0.496
−0.297
805
11467379

etodolac
20
−0.369
−0.632
−1.397
−0.661
1.194
0.212
0.014
0.063
−0.094
805
11489203

niacin
32.5
−1.128
2.434
0.087
0.742
−0.544
0.736
−0.220
0.000
−0.660
806
11468029

nipecotic acid
30.96
−0.273
0.241
0.512
0.606
0.591
−0.082
1.014
0.734
1.386
806
11468098

niacin
20
0.028
−0.274
−1.746
0.757
0.593
1.132
−0.404
−0.363
−0.467
806
11487822

nipecotic acid
20
−0.551
0.735
−0.516
−0.580
0.362
−1.276
−0.704
−0.455
−0.995
806
11489000

amprolium
16.44
−0.583
1.227
−0.304
0.135
1.134
0.126
0.136
0.195
−0.055
807
11467156

amprolium
20
0.292
0.035
−1.124
−1.025
0.560
1.268
0.243
0.205
0.210
807
11487938

nortriptyline
15.18
−0.668
0.209
−2.020
−0.399
−0.159
0.157
−0.292
−0.233
−0.354
809
11467402

nortriptyline
20
−1.564
1.097
−1.905
−1.277
0.461
0.136
0.542
0.545
0.506
809
11488813

antimycin A
20
−0.971
−0.604
−1.390
0.520
0.400
−0.791
−1.380
−1.319
−1.168
810
11488903

pregnenolone
20
−0.360
0.445
1.358
0.286
0.338
0.971
−1.061
−0.586
−1.854
811
11488758

griseofulvin
20
0.008
−2.024
−1.919
0.065
−1.037
−1.343
0.341
0.068
0.782
812
11488029

estradiol diacetate
20
−0.748
0.784
−0.624
−0.924
1.404
0.396
0.379
0.457
0.148
813
11489253

miconazole
9.62
−1.008
−0.397
−1.491
−0.401
1.628
0.802
−0.955
−1.052
−0.619
814
11467215

miconazole
20
−0.134
0.051
−0.885
0.765
1.933
−0.524
0.078
0.136
0.013
814
11488864

DEET
20
−0.046
−0.064
−1.052
−0.574
0.608
0.065
−0.830
−0.631
−1.009
815
11488888

xylometazoline
16.36
−0.348
−0.122
−1.163
−0.584
0.378
1.079
−0.694
−0.650
−0.696
816
11467371

xylometazoline
20
−0.870
0.050
−0.710
−1.094
0.720
−0.231
−0.478
−0.223
−0.915
816
11488761

pyrithyldione
23.92
0.815
2.084
−0.650
−0.254
0.035
−0.828
−0.724
−0.504
−1.035
818
11467951

pyrithyldione
20
−0.767
−0.173
0.262
0.351
−0.612
0.514
−0.245
−0.531
0.394
818
11489336

dicyclomine
12.92
−0.420
−0.599
−0.626
−1.142
2.249
−0.146
0.074
−0.111
0.391
819
11467196

dicyclomine
20
0.195
1.104
−0.650
0.053
1.345
−0.506
−0.098
−0.166
0.106
819
11488406

cloxyquin
20
0.366
−0.163
−0.651
0.049
−0.294
0.920
−1.054
−1.128
−0.618
820
11488947

saccharin
20
−0.178
0.908
−0.357
−0.895
0.429
0.336
0.192
0.283
−0.035
821
11489248

neostigmine
17.92
0.205
−0.066
0.641
−0.516
0.904
0.368
−0.244
−0.340
0.007
822
11467616

neostigmine
20
−0.604
0.055
1.344
−0.614
1.299
−0.193
−3.767
−3.541
−3.446
822
11489094

vincamine
11.28
−0.087
0.840
−0.748
−0.828
0.777
−0.176
0.283
0.204
0.410
824
11467784

vincamine
20
−0.819
−0.619
−0.445
−0.717
0.244
0.118
0.003
0.039
−0.073
824
11489154

carbidopa
20
−2.898
−0.867
−2.142
−2.029
−0.183
−1.954
−1.088
−0.788
−1.420
825
11488931

flurandrenolide
20
−0.657
0.660
−1.532
−0.468
−0.175
−0.391
0.147
−0.012
0.506
826
11488792

suxibuzone
9.12
0.782
0.650
−1.407
−0.303
1.080
0.217
0.047
0.066
0.009
827
11467806

suxibuzone
20
0.036
0.114
−1.112
0.149
0.446
0.786
−0.032
0.342
−0.704
827
11488782

gossypol
7.72
−1.515
0.664
−1.899
−1.136
0.616
0.050
0.116
0.403
−0.474
829
11467825

gossypol-acetic acid complex
20
−1.769
0.687
−0.514
−0.562
0.036
−0.783
−0.993
−0.832
−1.124
829
11489288

gossypol
20
−1.858
−0.945
−1.094
−1.739
−0.831
−0.344
0.481
0.719
−0.055
829
11489440

pyrilamine
14.02
0.003
0.003
−0.365
−0.643
0.610
0.189
−0.112
−0.200
0.097
830
11467437

pyrilamine
20
−0.394
−0.177
−0.681
−1.143
0.082
−0.520
−0.339
−0.270
−0.421
830
11489122

aminothiazole
20
0.434
−0.453
0.282
−0.203
−0.192
−0.795
0.910
0.981
0.567
831
11488695

1,3-dipropyl-8-cyclopentylxanthine
20
−0.311
−0.355
−1.261
−0.485
0.379
−0.922
−1.351
−1.137
−1.470
832
11489624

timolol
20
−1.197
0.603
−1.677
−0.712
0.291
0.183
−0.502
−0.341
−0.725
833
11489150

bethanechol
24.82
−0.527
0.785
−0.769
−0.302
0.403
0.427
−0.146
−0.255
0.087
834
11468221

bethanechol
20
−0.241
−0.837
−0.432
−0.617
0.600
0.461
−0.002
−0.234
0.421
834
11487948

aceclidine
20
−0.803
−0.537
−1.930
−0.779
0.704
0.088
−1.118
−1.208
−0.638
835
11489051

racephedrine
20
−0.482
0.052
−0.260
−1.006
0.267
−0.266
−0.174
−0.169
−0.151
836
11489125

ethoxyquin
18.4
−0.683
−0.391
−1.947
−0.140
−1.587
0.143
−0.796
−0.799
−0.640
837
11467913

ethoxyquin
20
−0.755
0.497
−1.530
−0.482
−0.693
−0.284
−0.318
−0.536
0.190
837
11489200

oxybenzone
17.52
−0.183
2.061
0.413
0.031
−0.335
−0.524
−0.344
−0.303
−0.371
838
11468035

oxybenzone
20
0.101
−0.222
−1.049
−1.001
0.569
0.440
−0.803
−0.675
−0.836
838
11488824

acyclovir
17.76
0.037
0.945
−0.982
−0.750
−0.531
−0.016
−0.140
−0.071
−0.299
839
11467234

acyclovir
20
−1.461
0.290
−1.615
−0.907
0.478
1.195
−0.497
−0.363
−0.667
839
11489379

nafcillin
20
−0.907
0.089
−2.111
−0.682
0.769
0.010
0.655
0.580
0.727
840
11488253

benfotiamine
20
0.558
0.946
−1.712
−0.514
−0.288
−0.291
−0.052
0.056
−0.268
841
11489341

methimazole
20
−0.250
−0.309
−0.088
−0.276
0.484
1.745
−0.212
−0.013
−0.500
842
11489089

desipramine
15.02
0.006
−0.720
−1.416
−0.586
1.201
−1.172
−1.845
−1.825
−1.511
844
11467491

desipramine
20
−0.166
−1.007
−1.581
0.147
−0.521
−0.230
0.029
0.087
−0.154
844
11487907

ritanserin
20
0.584
−1.308
−0.230
1.734
0.481
−0.198
−0.452
−0.391
−0.478
846
11489376

nerol
20
−1.107
−0.034
−0.445
−0.485
0.605
0.242
−0.601
−0.604
−0.484
847
11488600

hydrocortisone acetate
20
−0.916
0.132
−0.972
0.474
0.426
−1.461
0.558
0.403
0.836
848
11488846

trazodone
10.76
−0.035
0.143
−1.152
−0.093
0.052
0.028
−0.711
−0.542
−0.913
850
11467440

trazodone
20
−0.555
−0.050
−0.933
−0.470
0.256
0.038
−1.084
−0.904
−1.252
850
11488670

ethaverine
10.12
2.811
−0.212
−1.204
−0.070
−0.384
−1.076
−0.177
−0.160
−0.179
852
11467978

ethaverine
20
2.154
−1.478
−2.323
0.996
−0.501
−0.474
−0.388
−0.389
−0.304
852
11489201

aminophylline
22.2
−0.239
0.608
−0.274
0.309
0.982
0.177
−0.347
−0.287
−0.406
856
11467968

theophylline
22.2
−1.365
−0.560
−1.045
−0.775
0.571
−0.061
−0.063
−0.107
0.042
856
11468021

theophylline
20
0.374
−0.122
−0.436
0.250
0.062
0.379
0.260
0.295
0.114
856
11488658

benzyl benzoate
20
0.328
−0.081
−0.729
−0.596
−0.086
0.394
−0.734
−0.765
−0.489
857
11488348

dropropizine
16.92
−0.965
1.439
−0.480
−0.580
0.111
0.335
0.283
0.417
−0.044
858
11467393

dropropizine
20
−1.041
0.541
−1.015
0.418
0.422
1.315
−0.985
−0.814
−1.068
858
11488781

cyproterone acetate
20
0.325
0.041
0.289
−0.603
0.917
−0.625
0.003
−0.497
1.096
859
11489086

pyridostigmine
20
−0.051
1.178
−0.077
−0.994
−0.162
0.591
−0.631
−0.421
−0.947
860
11488677

captopril
20
0.422
−0.540
−0.989
−0.275
0.598
0.819
−0.605
−0.262
−1.112
861
11489027

cetrimonium
20
−4.937
−8.079
−5.775
−3.527
−2.664
−4.872
−1.380
−2.697
1.657
862
11488246

1-[(4-chlorophenyl)phenyl-methyl]-4-methylpiperazine
13.3
−1.138
−0.108
−1.566
−0.780
1.886
0.675
−0.214
−0.260
−0.085
863
11467854

THIP
28.54
0.156
0.846
−0.213
0.063
0.109
−0.673
−0.432
−0.377
−0.473
864
11468120

gaboxadol
20
−0.610
−0.252
0.416
−0.077
0.376
0.752
0.326
0.228
0.472
864
11489406

tolmetin
15.54
−1.012
−0.410
−1.908
−0.662
0.814
0.088
0.367
0.391
0.234
865
11468004

tolmetin
20
0.563
0.424
−1.321
0.135
0.316
0.182
−0.091
−0.029
−0.133
865
11489021

dinitolmide
20
−1.655
0.397
−0.993
−1.043
0.711
0.218
0.063
0.097
−0.028
866
11488493

sulfapyridine
16.04
−0.448
−0.546
−1.846
−0.611
0.402
0.167
−0.242
−0.216
−0.258
867
11467910

sulfapyridine
20
−0.646
−0.315
−0.450
−0.890
−0.698
−0.028
−0.603
−0.736
−0.211
867
11489139

ethosuximide
28.34
0.606
1.098
−0.713
−0.159
0.812
0.241
−0.154
−0.111
−0.257
869
11467313

ethosuximide
20
−0.439
0.423
−1.120
−0.581
−0.295
0.955
−0.096
−0.032
−0.199
869
11489299

alpha-cyano-4-hydroxycinnamic acid
20
−0.715
0.044
−0.415
−0.897
1.528
0.428
0.977
1.207
0.273
870
11489763

sulconazole
10.06
2.207
0.795
−0.878
0.548
−0.780
−1.787
0.114
0.143
0.024
871
11467958

sulconazole
20
−0.615
−0.181
−1.687
0.306
0.623
0.252
0.111
−0.068
0.453
871
11489238

adiphenine
12.84
−0.958
0.475
−1.815
−0.767
1.848
0.005
−0.347
−0.337
−0.337
872
11467223

drofenine
12.6
−0.398
−0.672
−0.071
−0.725
1.212
−0.555
−0.686
−0.839
−0.237
872
11467937

drofenine
20
−0.776
1.146
−1.273
−0.478
0.766
−0.459
−0.215
−0.080
−0.378
872
11488791

adiphenine
20
0.748
0.187
−0.046
−0.414
0.462
−0.052
0.746
0.994
0.100
872
11489333

folinic acid
8.44
0.225
0.385
−1.631
−0.787
0.626
0.217
−0.201
0.073
−0.715
873
11467886

leucovorin
20
−0.829
−0.537
−1.686
−0.840
1.147
0.710
0.546
0.533
0.404
873
11487932

alanyl-DL-leucine
20
−0.659
1.172
−0.857
−0.474
0.234
0.062
−0.233
−0.145
−0.365
874
11489170

oxytetracycline
8.68
0.029
−0.781
−1.129
−1.245
0.484
−1.500
0.442
0.110
1.021
876
11467455

oxytetracycline
20
0.398
1.384
−1.134
0.039
0.702
−0.052
−0.090
−0.272
0.372
876
11488804

clofibric acid
18.64
0.273
−0.471
−0.958
−0.372
−0.088
0.840
−0.231
0.097
−0.837
877
11467931

clofibric acid
20
−0.594
0.332
−0.645
−0.446
1.577
0.364
0.503
0.640
0.066
877
11487973

sulfacetamide
18.68
−0.387
0.792
−0.835
−0.530
0.957
−0.793
−1.595
−1.634
−1.255
878
11467162

sulfacetamide
20
−0.436
0.539
−1.601
−0.433
0.916
0.168
−0.496
−0.528
−0.331
878
11489134

norepinephrine
20
−0.497
0.896
−1.680
−1.218
0.595
−0.296
0.129
0.343
−0.251
879
11488880

hydrocortisone sodium phosphate
20
−0.433
0.163
−0.338
0.227
1.136
−0.963
−1.063
−1.143
−0.605
881
11488836

azithromycin
20
0.362
−0.058
−1.400
0.138
0.213
−0.272
0.145
0.281
−0.150
882
11489398

phenethicillin
10.98
0.583
1.325
−0.792
−0.639
−0.167
−0.388
−0.070
−0.044
−0.116
883
11467871

phenethicillin
20
−1.294
−0.099
−0.749
−0.681
−0.056
1.599
0.385
0.572
−0.074
883
11489153

pheniramine
16.64
−1.261
0.159
−1.080
−0.624
0.807
0.142
−0.600
−0.558
−0.606
884
11467207

pheniramine
20
−0.297
−0.332
−0.677
−1.027
1.461
0.030
0.015
0.052
0.005
884
11489093

amoxepine
12.74
−0.392
0.116
−1.674
0.000
0.687
−3.399
−0.163
−0.119
−0.270
885
11467250

amoxepine
20
−1.525
−3.135
−4.378
0.225
−1.877
−0.073
−0.415
−0.391
−0.305
885
11489061

cinchonine
20
−1.015
0.396
−2.294
−0.760
0.846
−0.198
−0.505
−0.508
−0.354
886
11488410

sulfamethoxypyridazine
14.28
−0.260
2.118
−1.443
−0.906
−0.551
0.465
−0.244
−0.137
−0.423
887
11467872

sulfamethoxypyridazine
20
−1.373
−0.276
−1.140
−0.525
1.086
1.355
0.031
−0.178
0.457
887
11489245

isopropamide
11.32
−0.781
−0.113
−1.046
0.074
0.128
0.760
−0.445
−0.399
−0.453
888
11467918

isopropamide
20
0.500
0.121
−0.876
−0.072
1.374
−0.890
0.557
0.643
0.333
888
11488867

pyrazinamide
32.5
−1.021
0.394
−1.589
−0.899
1.562
0.315
−0.920
−0.707
−1.178
889
11467662

pyrazinamide
20
−1.060
−0.059
−0.218
−0.672
−0.041
−0.043
−0.560
−0.564
−0.444
889
11489121

(R)-naproxen sodium salt
17.38
0.632
0.405
0.325
−0.253
−0.736
0.444
−0.254
0.135
−0.984
890
11467939

naproxen
20
0.029
1.749
0.134
0.903
0.583
0.709
−0.468
−0.192
−0.871
890
11488859

desoxycorticosterone acetate
20
0.272
0.757
−0.903
−0.625
1.339
0.070
−0.054
−0.073
0.039
891
11488232

acriflavinium hydrochloride
20
−0.949
−4.061
−4.725
−4.924
5.023
6.421
−0.846
0.240
−2.906
892
11487882

octopamine
26.12
−1.084
−0.385
−0.201
0.058
0.440
0.632
0.462
0.113
1.082
893
11468097

octopamine
20
0.482
0.006
−0.664
−0.763
−0.323
−0.649
−0.237
−0.111
−0.504
893
11488038

cyclophosphamide
20
0.038
1.271
−0.818
−0.026
1.115
−0.088
−0.794
−0.800
−0.548
894
11488962

naringin
6.9
−0.074
−0.461
−1.163
−0.555
0.688
−0.005
−0.196
−0.153
−0.241
895
11467615

guaifenesin
20.18
−0.012
−0.442
−1.923
−0.888
−0.163
0.480
−0.687
−0.558
−0.811
896
11467924

guaifenesin
20
−1.514
0.515
−1.306
−1.012
0.746
−0.165
0.089
0.196
−0.069
896
11488920

retinyl palmitate
20
−0.943
0.219
−1.690
−0.892
1.074
−0.170
−0.601
−0.509
−0.672
897
11489380

acetyl tyrosine ethyl ester
20
−0.951
−0.040
−1.391
−0.587
0.279
0.144
−0.191
−0.294
0.068
898
11489161

apomorphine
14.96
0.289
−0.520
−0.641
−1.080
−0.448
0.262
−0.467
−0.342
−0.685
899
11467249

tenoxicam
11.86
−0.940
−0.251
−1.037
−0.912
1.391
0.017
−0.797
−0.761
−0.724
900
11467675

tenoxicam
20
−0.463
−0.188
−0.698
−0.118
1.260
−0.263
−0.518
−0.572
−0.236
900
11488896

chlortetracycline
8.36
−0.009
−0.150
−0.740
−0.228
0.234
1.470
0.221
0.150
0.275
901
11467293

chlortetracycline
20
0.391
0.875
0.026
0.339
−0.390
0.005
−0.076
0.198
−0.636
901
11488618

furegrelate
20
−0.903
1.494
−1.018
−0.500
−0.898
0.520
0.166
0.267
−0.085
902
11489260

fenbendazole
20
−0.398
−1.895
−3.769
−0.360
−0.797
−1.535
0.339
0.350
0.186
903
11487856

piracetam
28.14
−0.740
0.674
−1.080
−0.509
0.945
0.118
−0.513
−0.413
−0.612
904
11467685

piracetam
20
−1.349
−0.321
−1.691
−0.835
0.359
−0.008
−0.486
−0.162
−0.974
904
11488890

novobiocin
20
−0.074
1.360
−1.637
−0.409
0.912
0.178
−0.266
−0.148
−0.371
905
11488793

glucosamine
20
−0.796
−0.122
−0.765
0.282
0.670
−0.446
−0.597
−0.792
−0.019
906
11488335

xanthurenic acid
20
0.001
0.312
−0.448
−0.328
2.263
0.322
1.482
0.929
2.255
907
11487974

berberine
11.9
−1.320
−3.912
−3.349
−1.161
−1.789
−1.873
−0.836
0.473
−3.343
909
11467734

berberine
20
−1.268
−4.055
−2.731
−0.022
−2.291
−1.103
−2.301
−0.630
−5.281
909
11488710

metergoline
20
2.185
1.154
−0.394
0.542
−0.322
0.464
−0.831
−0.817
−0.720
910
11488698

tuaminoheptane
20
−0.503
0.784
−0.807
−0.599
0.062
0.317
−0.440
−0.446
−0.277
911
11488363

propylthiouracil
23.5
0.265
0.419
−1.364
−0.885
0.550
0.762
−0.336
−0.037
−0.879
912
11467642

propylthiouracil
20
−1.184
0.081
−0.209
−0.455
0.730
0.717
−0.187
−0.166
−0.205
912
11489118

uridine triphosphate
20
−1.493
0.343
−1.167
−0.931
0.710
0.008
−0.698
−0.758
−0.392
913
11488341

aloin
20
−0.202
0.866
−0.001
−1.874
1.317
0.723
0.325
0.339
0.195
914
11489753

diclofenac
13.5
−0.577
−0.773
−1.841
−0.575
0.550
0.770
−0.040
−0.136
0.163
915
11467742

diclofenac
20
−0.153
−0.098
−1.012
−0.809
−0.726
0.353
0.156
0.356
−0.208
915
11488807

bendroflumethiazide
9.5
−0.260
−0.339
−0.886
−0.479
0.375
0.532
−0.350
−0.149
−0.693
917
11467932

bendrofumethiazide
20
0.545
0.789
−0.808
−0.223
0.027
0.025
−0.175
−0.224
−0.052
917
11489340

metolazone
10.94
−1.024
0.295
−1.290
−0.645
−0.232
0.416
−0.834
−0.884
−0.613
918
11467260

metolazone
20
−0.785
0.519
−0.787
−0.295
1.525
0.250
−1.310
−1.006
−1.631
918
11489557

sulpiride
11.72
−1.374
0.210
−1.069
−1.106
1.072
−0.307
−0.479
−0.274
−0.848
920
11467204

hexetidine
11.78
0.466
0.041
−0.445
−0.819
0.506
1.554
−0.199
−0.254
−0.053
922
11467699

hexetidine
20
−0.103
0.307
−0.144
−0.178
0.543
0.428
−0.359
−0.132
−0.761
922
11488769

allantoin
25.3
0.126
1.392
−0.125
0.291
0.670
−0.389
−1.230
−1.136
−1.233
923
11467150

allantoin
20
0.212
0.038
−0.707
−0.178
0.360
0.829
0.901
0.865
0.732
923
11488035

1-phenylbiguanide
20
−0.283
0.801
−0.680
0.254
0.605
−1.113
0.136
0.032
0.397
924
11489006

N-methyl (−)ephedrine
20
0.576
0.721
0.526
−0.068
1.190
0.065
0.292
0.437
0.018
925
11489012

dantron
20
−1.019
0.712
−1.565
−1.152
1.067
0.404
−0.515
−0.457
−0.492
926
11488419

clemastine
11.64
−0.611
−0.127
−0.699
0.029
0.597
−0.693
0.134
0.024
0.344
927
11467454

clemastine
20
−1.946
−1.286
−0.522
−0.630
−0.038
−0.437
−0.961
−0.954
−0.813
927
11488505

phenylmercuric acetate
20
−5.759
−7.229
−6.035
−3.739
−3.333
−3.937
ND
ND
ND
928
11488759

naloxone
12.22
−0.717
0.222
−0.356
−0.181
0.124
0.610
−0.445
−0.271
−0.753
929
11467259

tolperisone
20
0.208
0.166
0.121
−0.742
0.169
0.231
0.266
0.282
0.170
930
11488667

hydrochlorothiazide
13.44
−0.128
2.087
0.208
0.055
0.150
−0.784
0.006
0.079
−0.180
931
11467157

hydrochlorothiazide
20
−0.515
1.005
0.142
0.081
1.061
0.678
0.121
−0.077
0.566
931
11488856

lysyl-tyrosyl-lysine acetate
20
0.623
1.667
−0.071
0.025
−0.231
0.305
0.044
0.265
−0.362
932
11488370

scopolamine
20
−0.457
0.222
−1.061
−0.720
−0.305
0.547
−0.130
−0.060
−0.236
933
11489129

sulfamethazine
14.38
−0.189
0.662
−2.022
−0.527
0.284
0.504
−0.263
−0.192
−0.359
934
11467923

sulfamethazine
20
0.400
0.399
0.144
−0.945
0.049
0.045
−0.040
−0.110
0.105
934
11489137

erythromycin
20
−1.364
0.625
−0.660
−0.336
1.091
0.042
−0.155
−0.183
−0.086
935
11488575

erythromycin stearate
20
−0.693
1.313
−0.735
−0.415
0.248
0.377
−0.765
−0.506
−1.068
935
11489079

glafenine
10.72
0.145
0.341
−1.287
−0.299
0.895
0.046
−0.938
−0.772
−1.096
936
11467441

glafenine
20
0.436
0.057
−1.536
−0.282
0.248
0.289
0.070
0.100
0.000
936
11489199

propiomazine
20
−0.631
−0.190
−0.200
−0.457
1.024
−0.368
−0.901
−0.922
−0.695
937
11488746

triprolidine
14.36
−0.362
−0.343
−1.007
−0.687
0.468
−0.487
0.398
0.457
0.219
938
11467410

triprolidine
20
−1.177
−0.079
−0.841
−0.733
0.106
0.464
−1.449
−1.407
−1.272
938
11488661

mefenamic acid
16.58
−0.200
−0.654
−1.115
−0.874
1.232
0.645
−0.921
−0.866
−0.885
939
11467202

mefenamic acid
20
0.265
0.808
−1.055
0.343
0.812
−0.377
−0.010
0.038
−0.148
939
11489757

oxyphenbutazone
12.34
1.015
1.839
1.101
−0.345
−1.738
0.009
−1.275
−1.009
−1.587
943
11468197

oxyphenbutazone
20
−0.624
0.112
−0.740
−0.455
−1.341
−0.261
0.468
0.632
−0.022
943
11487969

sulfaphenazole
12.72
0.008
0.615
−1.364
−0.150
0.517
0.259
−0.733
−0.478
−1.156
944
11467169

sulfaphenazole
20
−0.557
−0.222
−1.608
−0.517
0.457
0.385
−0.702
−0.808
−0.398
944
11489759

flumethasone
20
−1.119
0.128
−1.641
−0.276
0.552
0.021
−0.255
−0.332
0.042
945
11489081

etanidazole
18.68
0.304
1.433
−0.755
−0.106
0.456
−0.352
−0.518
−0.176
−1.102
946
11467797

etanidazole
20
0.378
0.399
−0.963
0.547
0.710
0.585
0.484
0.559
0.207
946
11488726

phenindione
18
−0.467
−0.314
−1.060
−0.884
0.415
−0.504
0.268
0.384
−0.018
948
11467686

phenindione
20
−0.732
0.166
−0.880
−0.494
0.375
−0.091
0.457
0.146
1.082
948
11488815

kynurenic acid
20
−0.228
0.451
−0.914
−0.362
−0.143
0.757
−0.292
−0.194
−0.436
949
11489158

parachlorophenol
20
0.247
2.451
−0.668
0.782
1.436
0.036
−0.158
−0.090
−0.190
950
11488784

biotin
16.38
−0.264
1.174
−1.048
−0.435
0.639
0.776
0.069
0.422
−0.659
951
11467566

penicillamine
20
−0.469
−0.743
−0.735
−0.399
0.702
−0.400
−0.544
−0.497
−0.454
952
11488845

levonordefrin
20
−0.402
0.477
−1.614
−0.842
1.422
−0.288
0.626
0.780
0.260
953
11488871

benzylpenicillin
11.96
−1.082
−0.475
−0.542
0.043
−0.022
−0.688
−0.223
−0.276
−0.080
954
11468226

benzyl penicillin
20
−1.323
−0.169
−1.364
−0.496
0.551
−0.771
0.290
0.219
0.420
954
11488334

bromopride
11.62
−0.964
−0.735
−1.318
−0.682
0.648
0.556
0.137
0.141
0.113
955
11467852

bromopride
20
1.305
1.442
−0.793
−0.703
0.412
0.066
0.183
0.272
−0.040
955
11489343

cinoxacin
15.26
0.349
0.158
−0.562
−0.752
0.598
0.136
−0.196
−0.293
0.036
956
11467928

cinoxacin
20
0.595
−0.056
−0.785
1.067
0.254
−0.430
0.536
0.498
0.544
956
11488386

azaserine
20
0.962
0.847
−0.958
−0.570
0.951
1.220
0.010
0.142
−0.205
957
11489037

phenacemide
20
−0.803
−0.405
−0.661
−0.270
0.506
−0.638
−0.628
−0.528
−0.628
958
11488835

papaverine
11.78
−0.036
−0.710
−1.936
−1.024
−0.653
0.213
0.042
0.201
−0.293
959
11467731

papaverine
20
0.805
0.164
−1.548
−0.508
0.251
0.498
0.164
0.431
−0.332
959
11488794

methenamine
20
−0.695
0.559
−1.407
−0.763
0.752
−0.288
−0.224
−0.092
−0.465
960
11488643

noscapine
9.68
−0.264
1.733
−0.527
−0.196
0.408
1.142
0.193
0.305
−0.082
961
11467711

primidone
18.32
0.205
0.167
−0.306
−0.234
−0.056
0.296
−0.503
−0.305
−0.815
962
11468081

primidone
20
−1.078
1.784
−1.188
−0.357
−0.132
0.193
−0.784
−0.715
−0.768
962
11489109

piperacillin
7.72
−1.163
−0.185
−1.733
−0.785
0.366
0.392
−0.575
−0.714
−0.189
963
11467903

dacarbazine
21.96
−1.008
0.529
−1.457
−0.988
0.573
−1.444
−0.588
−0.551
−0.559
964
11467722

dacarbazine
20
−0.158
2.171
−1.023
0.461
0.614
1.072
−0.186
−0.180
−0.084
964
11488964

tolazoline
24.96
−1.209
−0.447
−1.058
−0.335
1.649
0.518
0.179
−0.117
0.702
965
11467208

tolazoline
20
1.163
0.855
−1.583
−0.106
−0.280
0.507
−0.540
−0.543
−0.357
965
11489020

gluconolactone
20
−0.071
2.069
−0.946
−0.537
−0.031
0.618
−0.720
−0.830
−0.390
966
11489749

beta-carotene
20
−1.148
1.200
−1.352
−0.423
1.388
0.027
−0.186
−0.130
−0.192
967
11489072

phenylbutazone
20
−0.411
1.825
−0.468
0.867
0.633
0.755
−0.952
−0.826
−1.026
968
11489098

dibucaine
11.64
−0.456
0.524
−0.789
−0.398
0.810
0.922
−0.769
−0.761
−0.681
969
11467224

dibucaine
20
0.902
0.183
−0.032
−0.701
0.770
0.026
−0.230
0.091
−0.771
969
11488817

cineole
20
0.454
0.218
0.033
−0.396
−0.452
−0.082
0.552
1.081
−0.689
970
11488037

tolnaftate
13.02
−0.302
−0.585
−0.402
0.900
1.104
−0.676
−1.563
−1.816
−0.782
971
11467218

tolnaftate
20
−0.237
−0.027
0.442
1.065
0.949
0.429
−0.311
−0.306
−0.284
971
11488766

thiothixene
20
0.036
0.795
−1.708
−0.227
−0.324
0.307
−0.215
0.004
−0.624
972
11489149

anisindione
20
−0.786
−0.936
−1.956
−0.059
−0.202
0.552
−0.453
−0.598
−0.018
973
11488243

nafronyl
10.42
−0.813
−0.179
−0.493
−0.845
1.725
−0.907
0.515
0.429
0.595
975
11467525

nafronyl
20
−0.519
1.103
−0.544
−0.316
0.888
−0.255
−0.090
−0.083
−0.117
975
11488684

eserine
14.52
−0.546
0.823
−1.277
−0.295
0.483
−0.432
−0.100
0.136
−0.569
976
11467714

eserine
20
0.536
1.565
0.550
1.371
0.454
0.260
0.275
0.092
0.630
976
11488146

physostigmine
20
−1.141
0.478
−1.244
−0.544
1.002
0.767
0.331
0.298
0.310
976
11488573

physostigmine
20
−0.530
1.275
−0.353
0.254
0.383
1.523
−0.337
−0.286
−0.381
976
11489099

triamcinolone
20
−1.408
−0.080
−1.074
−0.458
0.484
0.087
0.217
0.162
0.261
977
11488765

methacholine
20
−0.187
0.243
−1.628
−0.396
0.495
0.373
−0.001
−0.093
0.140
978
11487831

pyrithione zinc
20
−5.339
−8.322
−6.284
−3.529
−2.405
−4.773
−3.250
−4.140
−0.770
979
11488778

doxycycline
20
−0.322
−0.568
−1.407
−1.355
0.943
0.435
0.215
−0.344
1.238
980
11487959

cetylpyridinium
20
−4.516
−6.696
−4.298
−2.898
−2.465
−3.857
−1.684
−2.717
0.819
981
11488276

bisacodyl
11.06
0.534
0.591
−0.647
−0.429
0.834
0.628
−0.168
0.044
−0.566
982
11467567

bisacodyl
20
−0.420
−0.678
−1.312
−0.091
1.930
−0.324
0.567
0.230
1.072
982
11487965

3-aminopropanesulphonic acid
20
−0.590
0.270
−1.038
−0.639
0.548
0.103
−0.431
−0.579
−0.047
983
11489225

medrysone
20
−0.119
−0.757
−0.168
−0.229
0.617
−0.214
−0.345
−0.260
−0.501
984
11487957

sodium p-aminosalicylate
20
−0.471
0.038
0.357
1.365
−0.427
−0.286
−0.174
−0.196
−0.153
985
11487817

creatinine
20
−0.905
0.482
−1.890
−0.752
0.502
0.775
−0.847
−0.777
−0.833
986
11488580

acetylglucosamine
20
0.500
1.126
−0.603
−0.599
−0.424
0.235
−0.386
−0.268
−0.548
987
11489169

melatonin
17.22
0.105
−0.726
−1.330
−0.631
0.057
0.187
0.017
0.046
−0.047
988
11467606

melatonin
20
−1.302
0.362
−0.916
−0.176
0.689
−0.540
−0.344
−0.445
−0.066
988
11489160

arcaine
23.22
−0.483
−1.017
−0.864
−0.118
0.458
0.289
0.548
0.657
0.223
989
11468024

arcaine
20
−0.781
0.634
−0.583
−0.696
0.485
0.438
−0.874
−0.949
−0.517
989
11488417

carbetapentane
12
−1.812
−0.069
−0.968
−1.071
1.499
0.181
−0.201
−0.168
−0.223
990
11467535

carbetapentane
20
−0.529
0.411
−0.699
−0.737
0.751
0.439
−0.661
−0.663
−0.535
990
11489228

methylergonovine
20
−0.522
0.484
−1.322
−1.113
0.608
0.135
0.134
0.157
0.107
991
11488429

pilocarpine
19.2
−1.894
−0.189
−0.231
−0.246
0.442
0.267
−0.704
−0.683
−0.612
992
11467597

pilocarpine
20
−0.982
0.951
−0.296
−0.022
0.553
−0.617
−1.869
−1.707
−1.840
992
11489100

acetyltryptophanamide
20
−1.131
0.508
−0.574
−0.421
0.686
−0.369
0.556
0.622
0.314
993
11489162

canavanine
20
−0.464
0.587
0.856
−0.257
1.121
0.405
−0.073
−0.267
0.320
994
11488616

lincomycin
20
−0.335
−0.348
−1.812
−0.433
0.555
0.226
−0.263
−0.365
−0.048
995
11487921

oxidopamine
20
−0.607
0.079
−0.911
−0.781
0.702
−0.462
−0.311
−0.081
−0.635
996
11488834

mafenide
21.48
0.579
0.875
−1.132
−0.541
0.901
0.193
0.457
0.570
0.096
997
11467314

mafenide
20
0.172
−0.765
−1.529
−1.186
1.778
0.225
0.537
0.517
0.423
997
11487911

suloctidil
11.84
1.234
−3.733
−1.031
−0.073
−1.363
−4.302
−0.794
−0.535
−1.169
998
11467569

suloctidil
20
−5.538
−6.841
−3.516
0.897
−2.580
−0.200
−0.351
−0.082
−0.819
998
11489243

lomefloxacin
11.38
−0.420
−0.718
−0.692
−0.896
0.618
−0.062
−0.538
−0.642
−0.262
999
11467386

lomefloxacin
20
−0.549
0.815
−0.966
−0.974
0.732
−0.201
−0.884
−0.989
−0.502
999
11488512

trichlormethiazide
10.5
0.337
0.313
−1.914
−0.867
1.134
0.012
−0.132
−0.198
0.022
1000
11467973

trichlormethiazide
20
−0.452
−0.172
−0.230
−0.474
1.427
0.482
−0.656
−0.725
−0.393
1000
11488764

meclofenoxate
15.52
−0.665
0.254
−2.937
−0.681
0.244
0.233
−0.284
−0.265
−0.279
1001
11467911

meclofenoxate
20
−1.088
−0.199
−2.037
−0.865
1.685
0.206
0.669
0.577
0.777
1001
11488274

diphenhydramine
15.66
−1.330
−0.459
−1.616
−1.065
1.420
0.902
−0.485
−0.763
0.139
1002
11467213

diphenhydramine
20
−0.734
0.678
−0.657
0.951
0.696
0.018
−0.620
−0.450
−0.860
1002
11488777

7,8-dihydroxyflavone
20
−0.560
0.069
−0.633
−0.861
−0.473
0.609
1.304
1.580
0.448
1004
11488768

trihexyphenidyl
13.26
−0.848
0.293
−0.699
−0.642
1.169
−0.131
−0.397
−0.346
−0.423
1005
11467849

pridinol
13.54
0.737
0.046
0.600
−0.254
0.436
0.272
0.180
0.073
0.369
1005
11467947

trihexyphenidyl
20
−0.546
−0.482
−0.323
−0.583
0.673
0.359
−0.224
−0.192
−0.269
1005
11488645

pridinol
20
−1.349
−0.694
−1.080
−1.043
0.304
−0.767
0.892
1.147
0.188
1005
11489801

cytarabine
20
0.335
0.225
−1.460
−0.640
2.243
0.321
1.548
1.214
1.864
1006
11487975

L(−)-vesamicol
15.42
−1.137
0.104
0.241
0.219
−0.265
−0.597
−0.847
−0.941
−0.491
1008
11468068

methscopolamine
20
−0.033
0.066
−1.244
−0.165
0.226
−0.203
0.220
0.140
0.430
1009
11488878

trioxsalen
17.52
−0.830
−0.717
−1.142
0.059
0.920
0.088
0.087
0.279
−0.302
1012
11467857

trioxsalen
20
0.083
0.598
−1.440
−0.460
0.909
0.322
−0.828
−0.854
−0.541
1012
11488899

cresol
20
−0.895
0.322
−1.469
−1.127
0.649
0.808
−0.382
−0.326
−0.433
1013
11488581

nefopam
15.78
−0.091
−0.874
−1.042
−0.688
0.686
0.225
0.106
−0.140
0.543
1016
11467377

nefopam
20
−0.789
0.061
−1.349
−1.142
1.277
0.349
−0.857
−0.672
−1.059
1016
11489232

acetyltryptophan
20
−0.798
−0.284
−0.813
−0.592
0.503
−0.382
−0.550
−0.550
−0.440
1017
11489164

dextromethorphan
20
0.075
−0.432
−0.746
−0.515
0.358
0.395
0.241
0.373
−0.003
1018
11488837

carbamazepine
16.92
1.020
0.385
−1.902
−0.344
0.805
0.360
−1.277
−1.012
−1.608
1019
11467200

carbamazepine
20
1.887
−1.047
−2.228
−0.453
1.009
−0.634
0.007
0.176
−0.391
1019
11487941

pentamidine
11.76
−2.143
−4.070
−3.893
−0.932
−1.397
−1.865
−2.038
−1.261
−3.248
1020
11467701

pentamidine
20
−1.636
−3.221
−3.397
−1.306
−1.151
−2.196
−0.869
−0.621
−1.273
1020
11487971

neriifolin
20
−0.034
0.392
−0.435
−0.351
−0.062
0.711
−0.798
−0.822
−0.562
1021
11488349

citropten
20
−1.279
0.097
−1.290
−0.080
0.342
0.140
−0.358
−0.533
0.064
1022
11488630

N-methyl-D-aspartic acid
20
−0.482
−0.100
−0.376
−0.637
0.408
−0.275
0.240
0.210
0.260
1023
11489396

dibenzothiophene
20
−0.010
0.007
−1.120
−0.421
0.284
0.679
−0.451
−0.101
−1.006
1024
11488827

acetylphenylalanine
20
0.715
1.525
−0.051
−0.384
0.676
0.571
0.669
0.760
0.355
1026
11489168

nalbuphine
11.2
−1.178
−0.542
−1.290
−0.208
0.441
−0.613
0.285
0.696
−0.637
1027
11467266

rosolic acid
20
−0.618
0.479
−0.312
−1.145
−0.025
0.187
−1.477
−0.286
−3.643
1028
11488578

indoprofen
14.22
−1.226
−0.927
−2.111
−0.752
0.446
1.566
−0.251
−0.188
−0.321
1029
11467984

indoprofen
20
−1.164
−0.920
−0.622
−0.662
0.768
0.319
0.056
0.035
0.068
1029
11488601

fenoterol
13.18
0.195
0.115
−1.586
−1.093
0.259
−1.597
−0.265
−0.101
−0.549
1033
11467430

fenoterol
20
0.062
0.922
−0.379
−0.300
1.191
−0.262
0.071
−0.044
0.293
1033
11489204

acetylglutamic acid
20
−0.950
−0.372
−0.807
0.004
0.942
−0.444
0.310
0.166
0.560
1034
11489165

meclozine
10.24
0.016
0.594
−0.273
−0.139
1.378
−0.039
−0.711
−0.322
−1.358
1035
11467605

meclizine
20
0.628
−0.312
0.635
0.500
2.646
0.156
1.309
1.497
0.610
1035
11487926

enalapril
20
−0.352
0.288
−0.660
−0.050
0.099
−0.112
−0.678
−0.745
−0.406
1036
11489271

cefadroxil
11
−0.655
0.236
−1.404
−0.662
−0.125
0.223
−0.580
−0.400
−0.824
1037
11467582

cefadroxil
20
0.195
1.578
−1.221
0.414
0.399
0.289
−0.900
−0.914
−0.757
1037
11487903

oxotremorine
20
−1.489
−1.076
−0.215
−0.476
1.202
−0.261
−0.412
−0.366
−0.420
1038
11489384

eburnamonine
13.58
−0.759
0.053
−1.487
−0.487
0.351
0.126
0.126
0.007
0.349
1039
11467755

eburnamonine
20
−0.505
−0.483
−0.739
−0.267
0.275
0.287
−0.169
−0.061
−0.345
1039
11489320

prochlorperazine
10.7
0.496
0.031
−0.411
0.183
1.779
−0.482
1.093
0.911
1.254
1041
11467547

prochlorperazine
20
−0.374
−0.550
−1.926
1.205
1.894
0.405
−0.283
−0.426
0.062
1041
11489113

merbromin
5.66
1.019
1.139
−1.209
−2.986
4.234
21.904
−0.859
−0.695
−1.023
1043
11467935

merbromin
20
1.957
2.538
0.388
−3.495
8.568
18.194
−1.088
−0.783
−1.454
1043
11488449

ursodiol
20
−0.795
−0.134
−2.521
−0.320
1.682
0.756
−0.037
0.288
−0.702
1044
11488763

flumethasone
20
−0.733
−0.167
−0.816
−0.061
−0.544
−0.073
−0.133
−0.097
−0.178
1045
11489261

hecogenin
20
0.954
3.010
−0.948
0.106
0.155
0.715
−1.032
−1.077
−0.713
1046
11488379

promazine
14.06
−0.582
−0.563
−2.407
−0.926
1.386
−1.034
−0.079
0.052
−0.333
1047
11467841

promazine
20
−1.189
−0.312
−0.741
−0.318
0.777
−0.352
0.023
−0.041
0.124
1047
11488655

enoxacin
12.48
−1.019
0.405
−1.038
−1.177
1.209
0.386
−0.315
−0.250
−0.377
1048
11467501

enoxacin
20
0.085
0.467
−0.478
−0.685
0.722
0.243
−0.766
−0.582
−0.966
1048
11489547

chloroacetoxyquinoline
20
0.077
−0.386
−0.873
−0.690
0.479
−0.249
0.310
0.633
−0.444
1051
11488683

hydroquinidine
20
−0.694
−0.213
0.138
0.079
0.248
−0.272
0.120
0.020
0.300
1052
11489155

trimethobenzamide
10.3
−0.159
−0.172
−0.614
−0.232
0.500
−0.117
−0.319
−0.636
0.346
1053
11467228

trimethobenzamide
20
−1.465
0.148
−1.238
−0.636
−0.028
−0.050
−1.401
−1.261
−1.429
1053
11488660

clofoctol
20
−0.833
1.721
−1.149
−2.157
−1.502
−0.531
−0.681
−0.186
−1.558
1054
11489349

nadolol
12.92
0.347
−0.290
−0.846
−0.338
1.238
0.338
−0.387
−0.091
−0.915
1055
11467966

nadolol
20
−0.201
0.540
−1.549
−0.518
0.763
0.868
−0.452
−0.280
−0.714
1055
11489362

thioguanine
20
−0.940
0.920
−2.346
−0.835
−0.712
−1.454
0.683
0.967
−0.044
1056
11488511

procyclidine
13.92
−1.239
−0.211
−2.028
−1.028
0.256
0.610
−0.716
−0.771
−0.473
1057
11467992

procyclidine
20
−0.102
−0.064
−0.530
−1.291
1.339
−0.060
−0.545
−0.339
−0.848
1057
11489114

danazol
20
0.440
0.314
−1.138
0.168
−0.552
1.060
−0.252
−0.208
−0.221
1058
11488939

doxepin
20
−0.220
−0.287
−0.903
−0.646
1.002
−0.095
0.233
0.237
0.142
1059
11487949

pimethixene
13.64
−0.272
−0.127
−1.211
−0.885
0.869
0.397
−0.622
−0.499
−0.749
1060
11467442

triamterene
15.8
−0.864
−0.018
−1.059
−0.908
0.719
0.111
0.074
0.162
−0.156
1061
11467182

triamterene
20
−0.509
0.250
−1.578
−0.930
0.638
0.183
0.734
0.936
0.166
1061
11488754

methocarbamol
16.58
−0.807
1.160
−0.963
−0.530
1.555
0.308
−0.480
−0.731
0.084
1062
11467332

methocarbamol
20
0.036
2.654
0.511
−0.474
0.607
1.906
0.800
0.938
0.424
1062
11489088

dobutamine
20
−0.481
0.409
−1.565
−1.494
−0.972
−0.220
−0.633
−0.642
−0.487
1063
11489351

isosorbide
16.94
−0.812
−0.782
−1.334
−0.859
0.861
0.382
0.056
0.242
−0.336
1064
11467862

isosorbide
20
0.058
−0.265
−0.920
−0.657
1.447
0.448
0.109
0.156
0.066
1064
11488885

lobeline
20
0.485
0.734
−0.228
1.276
0.889
1.198
−0.945
−0.921
−0.810
1065
11489177

cefmetazole
20
−0.305
0.589
−0.867
−0.616
0.207
0.609
−0.291
−0.223
−0.376
1067
11489278

ranitidine
12.72
0.191
0.319
−1.831
−0.407
0.553
0.312
−1.078
−0.905
−1.263
1068
11467349

ranitidine
20
−1.609
0.291
−1.945
−0.794
0.816
−0.271
0.316
0.307
0.272
1068
11489241

pergolide
12.72
0.162
0.542
−0.962
−1.002
1.385
−1.011
−0.129
0.027
−0.425
1069
11467443

pergolide
20
0.335
−0.143
0.059
−0.706
0.930
0.336
0.188
0.085
0.321
1069
11489786

hexestrol
14.8
−0.712
−0.564
−1.841
−0.476
1.177
−1.006
−0.246
−0.198
−0.291
1070
11467847

hexestrol
20
1.429
−0.753
−2.041
0.418
−0.899
0.353
−0.952
−0.594
−1.518
1070
11488707

progesterone
12.72
0.392
−0.655
0.732
0.006
−0.413
−0.187
0.442
0.313
0.619
1072
11467625

alanyl-DL-phenylalanine
20
−0.406
0.328
−0.694
−0.366
0.348
0.241
−0.069
0.011
−0.218
1073
11489163

tropicamide
14.06
−0.740
−0.343
−0.819
−0.706
1.365
1.285
−0.349
−0.547
0.084
1075
11467376

tropicamide
20
−1.161
−0.307
−1.601
−0.954
1.207
−0.064
0.126
0.141
0.057
1075
11488752

xylazine
18.16
−1.082
−0.227
−1.261
−0.874
1.126
0.333
−0.296
−0.252
−0.315
1076
11467746

xylazine
20
0.639
0.226
0.174
−0.403
−0.036
−0.288
−0.292
−0.230
−0.361
1076
11489264

minocycline
8.74
−0.150
1.286
−0.919
−0.905
1.108
0.612
0.421
0.175
0.848
1077
11467463

minocycline
20
−0.640
1.387
−1.103
0.117
1.514
0.075
0.074
0.097
0.089
1077
11488863

levodopa
20.28
−0.654
1.146
−0.708
−1.811
0.543
0.483
0.265
0.400
−0.096
1079
11467165

levodopa
20
0.500
0.407
−1.040
−1.168
−0.031
1.093
−1.010
−1.107
−0.552
1079
11488312

D-phenylalanine
20
−0.947
−0.684
−1.086
−0.184
0.641
−0.427
−0.024
0.155
−0.371
1080
11489374

4-aminoantipyrine
19.68
0.567
0.926
−1.339
−0.304
−0.270
1.252
−1.099
−1.079
−0.975
1081
11467329

aminophenazone
20
−0.257
1.068
−1.344
−0.666
0.612
1.148
−0.513
−0.410
−0.634
1081
11488750

bromhexine
20
1.674
0.710
−1.434
0.026
−0.198
0.816
−0.463
−0.160
−0.994
1082
11489342

naphazoline
19.02
−0.526
0.689
−0.849
−1.091
1.495
−0.269
−0.127
−0.195
−0.009
1083
11467194

naphazoline
20
−0.110
0.869
−1.192
−0.530
0.644
−0.476
−0.316
−0.175
−0.480
1083
11488870

flutamide
14.48
−0.432
−0.194
0.389
0.034
1.704
1.332
−0.645
−0.689
−0.471
1086
11467328

flutamide
20
1.461
−0.360
−0.814
0.792
−0.018
0.121
−0.210
0.035
−0.594
1086
11489017

dichlorophene
20
0.136
−0.164
−0.524
−1.353
0.317
0.390
0.017
−0.193
0.503
1087
11489030

clomiphene
20
0.533
1.376
0.169
−0.381
1.174
0.025
−0.767
−0.538
−1.009
1088
11488955

clindamycin
20
0.050
0.714
−0.864
0.284
0.845
0.525
−0.601
−0.505
−0.697
1090
11488701

edoxudine
20
−1.208
0.396
−0.856
−0.637
0.867
−0.799
−0.747
−0.718
−0.687
1091
11489776

ampicillin
11.44
−1.225
−0.766
−1.864
−0.560
0.652
−0.307
−1.078
−1.037
−0.988
1092
11467262

ampicillin
20
−0.846
−0.258
−1.457
−0.776
1.396
0.060
−0.210
−0.043
−0.529
1092
11488585

sulfameter
14.28
−0.944
−0.666
−1.124
−0.109
0.220
0.087
−0.791
−0.572
−1.069
1094
11467917

sulfameter
20
−1.360
−0.049
−1.116
−0.655
1.210
−0.560
0.114
0.104
0.123
1094
11489244

benserazide
15.54
−0.141
−1.054
−0.598
−0.348
−0.106
−0.938
−0.065
−0.187
0.187
1095
11468086

benserazide
20
−2.722
−3.927
−2.336
0.303
1.417
−0.129
−1.291
−1.371
−0.930
1095
11487956

carnitine
20
0.421
1.410
0.245
0.847
0.548
0.664
−0.017
−0.007
−0.094
1096
11487825

hydrocortisone
20
0.064
0.783
−0.167
−0.395
0.001
0.320
1.153
0.961
1.241
1098
11488128

acexamic acid
20
−0.238
0.407
−0.698
−0.919
−0.149
−0.025
−0.926
−0.815
−0.995
1099
11488669

labetalol
12.18
−1.600
0.291
−0.721
−1.086
0.867
−0.075
0.078
−0.031
0.291
1100
11467425

labetalol
20
−0.153
0.411
−0.707
−1.038
0.010
0.137
0.453
0.564
0.126
1100
11488679

budesonide
20
−0.107
−0.165
−0.867
−0.542
0.279
−0.004
−0.318
−0.285
−0.277
1101
11488439

suprofen
15.36
−0.084
0.426
−1.379
−0.949
1.315
−0.859
−0.408
−0.147
−0.861
1102
11467964

suprofen
20
−0.963
−0.612
−0.667
−0.294
0.585
0.879
−0.202
−0.368
0.192
1102
11489246

sodium dehydrocholate
20
−0.058
−0.236
−0.875
−0.220
0.251
0.701
−0.139
−0.104
−0.124
1104
11488967

hycanthone
11.22
−0.738
−0.114
−1.626
−0.151
0.610
−1.292
0.860
0.837
0.741
1105
11467503

hycanthone
20
−1.418
−0.146
−1.485
−0.090
0.221
−0.009
−0.383
−0.138
−0.828
1105
11488494

flopropione
20
−0.260
0.869
−0.475
−0.473
0.270
1.173
−1.405
−1.255
−1.449
1106
11488770

cyclocreatine
20
−1.237
−0.225
−1.813
−1.176
0.957
0.848
0.152
0.262
−0.121
1107
11488741

antipyrine
21.26
−0.606
−0.249
−0.829
−0.523
1.394
0.898
0.573
0.636
0.287
1108
11467177

antipyrine
20
0.566
0.338
−0.565
0.962
1.384
0.053
1.453
1.345
1.324
1108
11487904

medroxyprogesterone
20
−0.629
−1.575
−1.060
−0.347
2.109
0.254
−0.968
−0.898
−0.981
1110
11487963

colistimethate
20
−0.769
0.698
−1.244
−0.613
0.817
−0.163
0.945
0.860
1.011
1111
11488891

disopyramide
11.78
0.158
−0.247
−1.356
−0.948
0.362
−0.068
−0.112
−0.010
−0.304
1112
11467414

disopyramide
20
0.221
1.221
−0.037
−0.536
−0.395
0.407
−0.403
−0.197
−0.679
1112
11488849

acemetacin
9.62
0.251
−0.358
−1.188
−0.769
1.639
0.313
−0.321
−0.494
0.093
1113
11467444

acemetacin
20
0.535
−0.630
−0.427
−0.722
1.088
−0.409
−0.016
0.038
−0.059
1113
11488978

benzthiazide
9.26
0.101
0.052
−1.733
−0.960
1.797
1.057
−0.581
−0.604
−0.422
1114
11467972

benzthiazide
20
0.498
−0.053
−0.755
−0.375
−0.253
−0.067
−0.438
−0.203
−0.768
1114
11488957

norethynodrel
20
−0.126
0.366
−0.861
−0.641
0.264
−0.058
0.093
0.116
0.109
1115
11488843

mercaptopurine
20
0.125
−2.053
−1.336
0.609
1.142
−0.431
−0.061
−0.159
0.098
1116
11487876

folic acid
20
−0.031
−0.200
−0.778
−0.291
0.228
−0.542
−0.368
−0.317
−0.401
1117
11489275

N-formylmethionylphenylalanine
20
0.205
0.383
0.154
−0.371
−0.333
0.092
0.487
0.607
0.225
1119
11489009

roxarsone
15.2
1.100
0.878
1.210
1.005
−0.366
0.274
0.333
0.320
0.288
1120
11468118

roxarsone
20
−0.711
0.274
−0.453
−0.478
2.262
0.874
0.835
0.763
0.865
1120
11488295

azobenzene
20
−0.872
1.236
−0.857
−1.081
0.275
0.149
0.717
0.787
0.439
1122
11489249

meclofenamic acid
13.5
−1.379
−0.490
−1.303
−0.965
1.148
0.208
−1.220
−1.337
−0.776
1123
11467354

sodium meclofenamate
20
0.317
−0.210
−1.445
1.124
1.308
−0.596
0.128
0.230
−0.033
1123
11488861

hyoscyamine
20
−0.646
−1.042
−0.732
−0.953
0.418
0.235
−1.165
−1.169
−0.988
1124
11487928

todralazine
17.22
−0.140
0.376
−1.412
−0.289
0.663
0.074
0.259
0.316
0.046
1125
11467219

todralazine
20
−0.520
1.082
−1.365
−0.503
−0.108
0.438
0.097
0.119
0.117
1125
11488963

phenytoin sodium
20
−0.113
1.189
−0.121
0.597
0.631
0.674
−0.810
−0.760
−0.760
1126
11489097

indapamide
20
0.701
0.658
−0.971
0.188
0.616
−0.659
0.235
0.152
0.433
1127
11488796

piromidic acid
13.88
0.960
0.501
−1.520
−0.452
1.051
−0.210
−0.254
−0.053
−0.618
1129
11467953

piromidic acid
20
−0.829
0.578
−1.525
−0.432
0.880
0.980
−0.243
−0.233
−0.219
1129
11489281

fluphenazine
9.14
0.095
−0.168
0.102
1.160
1.059
−0.074
0.802
0.639
0.989
1130
11467468

flufenazine
20
1.020
0.118
1.290
0.563
0.736
−0.485
0.487
0.386
0.675
1130
11489015

hydroflumethiazide
12.08
−0.321
1.235
−0.769
−0.610
0.790
−0.610
−1.026
−1.097
−0.731
1131
11467161

hydroflumethiazide
20
−0.676
0.157
−1.183
−0.378
0.618
0.369
−0.231
−0.177
−0.214
1131
11488826

chlorpropamide
14.46
−0.326
2.633
−0.291
0.368
0.287
0.928
−0.085
−0.101
−0.046
1132
11467471

chlorpropamide
20
−0.004
0.756
−0.045
0.986
1.009
1.558
0.969
0.769
1.127
1132
11487905

lysergol
15.72
−0.510
0.207
−1.006
−1.681
0.791
0.344
−0.745
−0.399
−1.318
1134
11467602

mitoxanthrone
9
−2.511
−1.146
−3.096
−0.273
−1.616
−6.280
0.039
0.013
0.084
1135
11467533

mitoxanthrone
20
−6.150
−5.230
−4.730
−2.820
−3.148
−1.242
0.121
−0.779
1.953
1135
11488724

hydrocortisone hemisuccinate
20
−0.936
−0.993
−1.102
0.140
0.566
−0.370
−0.432
−0.510
−0.106
1136
11489085

diethylstilbestrol
14.9
−0.705
−0.971
−2.051
−0.256
0.178
0.228
0.068
0.362
−0.525
1138
11467904

diethylstilbestrol
20
−0.300
−0.525
−1.931
−0.006
1.254
−0.250
0.673
0.698
0.437
1138
11487964

ethinyl estradiol
20
1.138
0.575
−1.972
−1.024
0.416
0.376
−0.421
−0.146
−0.832
1139
11488820

retinyl acetate
20
1.151
0.777
−0.672
−0.031
−0.007
0.772
−1.220
−1.077
−1.239
1140
11488317

benztropine
20
−0.529
−1.577
−2.046
0.055
1.455
−1.170
−0.332
−0.183
−0.624
1141
11487922

zidovudine
20
−1.328
−0.159
−1.105
−0.815
0.567
0.637
−0.345
−0.166
−0.667
1142
11488743

fenspiride
15.36
−0.076
0.370
−1.797
−0.502
0.830
−0.076
−0.481
−0.472
−0.448
1144
11467361

fenspiride
20
−1.248
0.927
−1.260
−0.708
0.880
−0.127
−0.323
−0.227
−0.452
1144
11489212

sulfanilamide
23.22
1.066
1.330
−0.944
−0.640
−0.379
−0.647
0.029
0.022
0.032
1146
11467877

sulfanilamide
20
−0.872
0.421
−0.772
−0.667
0.416
0.532
−0.397
−0.187
−0.773
1146
11488662

bergapten
20
−0.501
0.188
−0.679
−0.740
0.234
0.328
−0.412
−0.448
−0.211
1147
11488350

streptozosin
20
0.049
−0.382
−0.932
−0.257
0.042
0.717
0.137
0.024
0.271
1149
11487878

azelaic acid
20
−1.214
−0.024
−1.754
−0.890
0.433
−0.125
−0.501
−0.394
−0.554
1150
11488811

alpha-tochopherol
20
0.471
0.587
−0.595
0.447
0.323
0.544
−1.489
−1.206
−1.789
1151
11488538

tripelennamine
20
−0.871
0.257
−0.283
−1.094
0.920
1.663
−0.992
−0.897
−1.015
1152
11488773

strychnine
20
0.311
0.458
−0.684
0.051
0.490
0.031
0.699
0.729
0.448
1154
11487893

sulfabenzamide
14.48
−0.547
0.121
−0.357
−0.804
1.590
−0.031
−0.151
−0.115
−0.197
1155
11467859

sulfabenzamide
20
−2.139
0.688
−1.959
−0.602
0.078
0.410
0.120
0.187
−0.036
1155
11489133

gentisic acid
20
−0.811
0.666
−1.242
−2.086
0.540
0.210
−0.514
−0.406
−0.654
1156
11488589

ketoconazole
20
0.144
−0.607
−0.254
−0.327
1.704
0.109
−0.113
−0.313
0.253
1157
11487946

perhexiline
14.42
−0.143
−0.146
−1.391
−0.963
1.080
−4.917
0.239
0.350
−0.028
1158
11467434

perhexiline
20
−5.923
−8.143
−6.395
−3.988
−1.486
−0.729
−3.483
−4.037
−1.656
1158
11489355

sulfadiazine
15.98
−0.436
0.216
−1.326
−0.599
1.154
−0.501
−1.619
−1.536
−1.513
1159
11467171

sulfadiazine
20
−1.032
−0.063
−0.723
−0.299
1.058
0.301
−0.144
−0.263
0.133
1159
11489135

nifenazone
12.98
−0.606
−0.220
−2.019
−0.474
0.633
−0.977
−0.862
−0.909
−0.626
1162
11467373

nifenazone
20
0.123
0.371
−0.430
−0.210
1.445
−0.156
0.389
0.087
0.911
1162
11488676

naltrexone
20
0.167
0.046
−1.996
−0.374
0.817
0.312
0.200
0.396
−0.235
1163
11489363

diethylcarbamazine
20.08
−0.682
0.321
−1.825
−0.747
0.102
0.200
−0.219
−0.196
−0.230
1164
11467432

diethylcarbamazine
20
−0.556
0.154
−1.272
−0.352
0.059
0.308
0.586
0.706
0.297
1164
11488838

aminocaproic acid
30.5
−0.552
0.200
0.544
0.257
1.822
0.280
1.061
0.869
1.249
1167
11468108

6-aminocaproic acid
20
−0.572
−0.949
−0.672
−0.732
0.474
−0.680
−0.523
−0.316
−0.897
1167
11487947

estriol benzyl ether
20
0.551
2.168
2.975
3.459
−0.504
1.667
−0.114
0.122
−0.574
1168
11489258

norethindrone
20
−0.977
0.144
−1.543
−0.681
1.394
0.056
−0.684
−0.694
−0.459
1169
11488882

aspirin
20
−0.717
−0.668
−1.128
−0.523
0.336
−0.047
−0.390
−0.241
−0.579
1171
11489715

fenofibrate
11.08
−1.195
0.944
−1.105
−0.813
0.626
−0.542
0.389
0.325
0.442
1172
11467423

fenofibrate
20
−0.791
−0.278
−1.298
−0.064
0.401
0.279
0.279
−0.005
0.803
1172
11489206

imipramine
14.26
−0.842
0.714
−1.040
−0.215
0.993
−0.901
−0.442
−0.503
−0.282
1174
11467220

imipramine
20
−0.222
0.162
−1.230
−0.603
0.879
−0.672
0.134
−0.025
0.505
1174
11488806

sulfathiazole
15.66
−1.131
1.534
−0.404
−0.815
1.828
0.611
0.172
0.419
−0.398
1175
11467164

sulfathiazole
20
−1.556
0.653
−0.273
−0.504
−0.433
0.353
0.782
1.028
0.117
1175
11488657

ethambutol
20
−0.578
0.056
−1.099
−0.971
0.914
−0.012
−0.623
−0.462
−0.753
1176
11488830

sulfamerazine
15.14
−0.911
−0.008
−1.697
−0.719
0.577
−0.754
0.024
0.182
−0.301
1177
11467842

sulfamerazine
20
−0.611
−0.004
−0.919
−0.003
0.927
0.288
−0.480
−0.501
−0.339
1177
11489136

spiperone
10.12
−1.242
0.116
−3.128
0.096
−0.540
−0.992
−0.131
−0.030
−0.314
1180
11467436

spiperone
20
−1.435
−0.830
−2.328
−0.510
−1.311
−1.822
0.482
0.681
−0.020
1180
11489242

oxymetazoline
15.36
−0.605
−0.680
−1.062
−0.450
0.473
−0.717
−1.412
−1.673
−0.662
1181
11467372

oxymetazoline
20
−0.861
0.087
−1.251
−0.378
0.564
−0.757
−0.552
−0.540
−0.382
1181
11488814

adenosine phosphate
20
1.152
0.702
−1.145
0.139
−0.364
0.271
−0.531
−0.437
−0.552
1184
11489018

dapsone
16.1
−1.186
0.786
−0.540
−0.573
0.993
0.168
0.114
−0.004
0.282
1186
11467183

dapsone
20
0.099
0.024
−1.085
−0.470
0.366
0.139
−0.832
−0.698
−0.877
1186
11488949

estradiol-3-sulfate
20
−0.258
0.896
−0.606
−0.317
0.444
−0.697
0.718
0.735
0.589
1187
11488355

furosemide
12.1
0.801
0.877
−0.455
−0.374
1.307
0.234
−0.355
−0.292
−0.405
1188
11467489

furosemide
20
−1.396
0.768
−1.510
−0.787
0.313
0.342
0.198
0.309
0.011
1188
11488821

cefoxitin
9.36
−0.397
−0.321
−2.375
−0.659
0.739
0.000
−0.650
−0.732
−0.369
1189
11467980

cefoxitin
20
−1.166
0.444
−1.230
−1.202
0.253
−0.219
−0.195
−0.232
−0.092
1189
11488492

hydroxytacrine
20
−0.081
−0.060
−1.660
−0.541
1.330
0.143
−0.729
−0.736
−0.500
1190
11489031

chloroxine
20
−1.392
−1.831
−2.014
1.120
−2.934
−0.800
−1.089
−0.461
−2.181
1191
11488503

sulfisoxazole
14.96
−0.535
0.366
−1.140
−0.765
0.970
0.001
0.293
0.304
0.217
1192
11467482

sulfisoxazole
20
−1.895
0.384
−0.835
−0.543
−0.095
0.649
0.103
0.239
−0.187
1192
11489141

phenacetin
22.32
0.588
0.157
−1.856
−1.039
1.110
−0.611
−0.311
−0.148
−0.584
1193
11467681

phenacetin
20
0.665
1.310
0.760
−0.255
1.491
0.005
0.811
0.833
0.564
1193
11489756

strophanthidin
20
0.028
0.227
−0.828
−1.126
1.582
1.100
−0.232
−0.222
−0.231
1195
11488603

zaprinast
20
0.602
1.768
−1.175
−0.347
−0.482
0.226
0.076
0.220
−0.234
1196
11489263

azathioprine
20
−0.519
−0.888
−1.658
0.139
0.426
−0.533
−1.254
−1.242
−1.093
1198
11487884

N-formylmethionyl-leucylphenylalanine
20
0.354
2.059
−1.240
0.476
1.017
0.374
−0.370
−0.517
−0.051
1199
11487824

tranylcypromine
20
−0.673
−0.231
0.085
0.032
0.093
−0.318
0.008
−0.018
0.015
1200
11488776

trimethoprim
13.78
−1.021
−0.569
−0.979
−0.713
1.094
0.667
0.033
0.110
−0.166
1201
11467356

trimethoprim
20
−0.102
−0.450
−0.944
−0.733
1.375
−0.368
−0.189
−0.194
−0.149
1201
11488753

galanthamine
13.92
−0.383
1.321
−0.377
−0.543
1.301
−1.112
−0.338
−0.310
−0.312
1202
11467736

methacycline
9.04
0.323
2.538
−0.031
−0.517
0.261
0.020
0.913
0.781
0.984
1203
11468112

methacycline
20
−1.645
−0.365
−1.744
−1.616
1.083
0.723
−0.340
−0.600
0.258
1203
11489214

dihydroergotamine
20
0.293
0.585
−0.604
0.372
1.157
−0.494
0.008
−0.021
0.143
1204
11489004

lapachol
20
−0.409
−0.409
−1.211
0.035
−0.544
0.325
−1.316
−1.308
−1.077
1205
11489267

picrotoxinin
20
−1.116
0.141
−1.611
−1.064
1.094
0.172
−0.512
−0.408
−0.551
1206
11488901

chlorpheniramine
14.56
−1.458
0.060
−1.540
−0.945
0.521
0.080
0.504
0.533
0.308
1207
11467265

phenylephrine
20
−0.349
−0.455
1.105
−0.460
0.474
−0.187
0.254
0.120
0.536
1208
11489096

ketoprofen
15.74
−0.408
−0.207
−0.502
−0.432
1.026
1.538
0.103
−0.084
0.427
1209
11467367

ketoprofen
20
0.048
0.194
0.268
−0.241
0.545
0.119
−0.471
−0.428
−0.486
1209
11488772

probucol
7.74
−1.116
−0.447
−1.514
−0.459
0.627
−0.232
0.311
0.396
0.076
1210
11467532

probucol
20
−0.586
−0.915
−1.114
−0.142
0.464
−0.180
−0.053
−0.002
−0.136
1210
11489216

methoxyamine
20
−1.064
0.789
−1.833
−0.754
0.751
0.749
−1.274
−1.049
−1.494
1211
11488730

sulindac
20
0.777
0.793
−0.974
−0.591
0.107
−0.574
−0.304
−0.224
−0.401
1212
11489142

betahistine
29.38
−0.129
0.297
−0.984
−0.896
0.557
0.296
−0.175
−0.111
−0.280
1213
11467691

betahistine
20
1.068
1.977
0.861
0.125
−0.176
0.386
−0.284
−0.008
−0.718
1213
11489007

molsidomine
16.44
−0.281
−1.227
−1.312
−0.968
1.246
−0.533
−0.253
−0.168
−0.366
1214
11467695

molsidomine
20
−0.665
−0.269
−0.651
−0.537
−0.398
0.339
0.250
0.331
0.106
1214
11488994

fendiline
12.68
0.636
−0.301
0.307
0.421
1.303
−0.405
0.614
0.636
0.448
1215
11467418

fendiline
20
−0.080
0.842
−1.007
−1.174
0.912
−0.752
−1.005
−0.896
−0.951
1215
11488822

estriol
20
−0.020
1.939
−0.528
1.334
0.104
0.814
−0.307
−0.108
−0.583
1216
11488779

tetracaine
15.14
−0.370
0.665
−0.809
−0.119
−0.042
−0.536
−0.246
−0.058
−0.584
1218
11467719

tetracaine
20
−0.539
−0.220
−0.048
−0.492
0.320
0.383
−0.280
−0.376
−0.034
1218
11489144

norgestrel
20
−0.966
0.593
−0.761
−0.965
0.831
−0.027
−0.225
−0.183
−0.187
1219
11488823

(+)-bicuculline
10.88
−0.190
−0.677
−1.330
−0.852
0.256
0.300
0.304
0.163
0.533
1220
11467737

cyclopentolate
13.72
−0.114
−0.678
−0.400
−0.335
0.345
0.859
0.035
0.091
−0.093
1221
11468243

cyclopentolate
20
−0.300
0.293
−0.756
−0.072
−0.406
−0.283
0.556
0.830
−0.037
1221
11488938

theobromine
22.2
−1.067
−0.710
−0.948
−0.513
0.512
0.007
−0.141
−0.294
0.207
1222
11468022

theobromine
20
−0.264
0.392
−0.982
−0.847
0.179
−0.026
−0.561
−0.449
−0.609
1222
11488801

acebutolol
11.88
−0.383
−0.543
−0.837
−1.006
1.266
−0.884
−0.311
−0.431
−0.037
1223
11467217

acebutolol
20
−0.271
0.310
−0.548
0.016
1.061
0.214
−0.511
−0.591
−0.254
1223
11489156

estradiol cypionate
20
0.219
0.452
−2.428
−0.489
−0.010
0.408
−0.124
0.072
−0.418
1224
11488819

chrysin
15.74
1.243
1.238
0.370
0.765
−0.602
0.920
0.205
0.280
0.003
1225
11468037

chrysin
20
−0.802
0.097
−1.566
−0.941
0.949
0.655
−0.137
0.071
−0.552
1225
11488569

gamma-aminobutyric acid
20
1.043
−0.314
−0.777
0.550
0.209
−0.038
−0.119
0.212
−0.693
1227
11489024

thimerosal
20
−5.590
−8.416
−6.206
−3.315
−3.880
−5.732
2.733
−1.197
10.413
1228
11488368

N-acetylneuramic acid
20
1.009
0.869
−0.118
0.053
0.063
−0.254
1.061
1.111
0.813
1229
11488375

N-acetyl-L-leucine
23.1
−0.252
1.398
−0.698
−0.581
0.537
0.648
−0.316
−0.410
−0.067
1231
11468044

acetyl-L-leucine
20
−0.465
0.771
−0.804
−0.575
1.139
0.267
0.328
0.438
0.088
1231
11488291

tetrahydroxy-1,4-quinone
23.24
−1.006
−0.157
−1.965
−0.511
0.667
−0.785
−0.907
−0.979
−0.592
1232
11467983

tetroquinone
20
0.088
0.130
−0.574
−0.424
0.638
0.386
0.067
0.028
0.112
1232
11488682

peruvoside
20
0.426
0.065
−1.190
−0.906
0.997
0.075
0.328
0.297
0.324
1233
11489218

methylprednisolone
20
−0.631
−0.352
−1.014
−0.375
0.133
−0.102
−0.220
−0.138
−0.270
1234
11489090

chaulmoogric acid, ethyl ester
20
−0.015
−0.123
−0.612
−0.536
0.513
0.617
−0.730
−0.876
−0.265
1235
11488327

acetaminosalol
20
0.144
1.128
−0.142
−0.707
0.308
0.465
0.083
0.145
−0.060
1237
11489247

hexachlorophene
20
−3.480
−5.584
−1.203
−2.559
−3.378
−2.828
−2.471
−1.371
−4.169
1238
11488921

dyclonine
13.82
−0.872
0.108
−0.221
−0.746
0.775
0.597
−0.237
−0.137
−0.405
1240
11467412

dyclonine
20
−0.640
0.157
−0.882
−1.085
0.379
1.243
−0.690
−0.377
−1.117
1240
11488829

sulfaguanidine
20
−0.691
−0.667
−0.421
0.217
0.902
0.147
−0.571
−0.522
−0.556
1241
11489236

dipyrone
12.84
−0.607
0.325
−1.243
−0.738
−0.683
0.356
0.172
0.100
0.296
1242
11467861

dipyrone
20
−0.809
0.582
−1.908
−0.760
−1.148
0.337
−0.955
−0.930
−0.820
1242
11489369

floxuridine
20
−0.712
0.511
−1.643
−1.275
0.063
−0.314
0.909
0.993
0.539
1243
11488483

mepenzolate
11.74
−0.261
1.157
−0.744
−0.524
1.206
0.666
−0.318
−0.454
0.003
1244
11467801

mepenzolate
20
0.333
0.633
−0.894
1.198
0.368
0.855
−0.025
0.062
−0.129
1244
11488858

pipenzolate
11.28
−1.074
0.785
−0.654
−0.281
0.627
0.192
−0.473
−0.553
−0.217
1246
11467908

pipenzolate
20
0.001
1.043
0.060
−0.205
0.166
−0.954
−0.495
−0.411
−0.569
1246
11489330

bithionol
20
−2.247
−4.693
0.593
−2.723
1.449
−2.613
−1.531
−1.261
−1.838
1247
11487929

estrone hemisuccinate
20
−0.076
0.242
−0.686
−0.573
0.834
0.250
0.261
0.370
−0.003
1248
11489394

betaine
20
0.548
−0.215
1.036
0.345
−0.348
−0.998
0.478
0.354
0.604
1249
11488696

methoxyvone
20
0.596
−1.793
−0.620
0.104
0.512
0.419
−0.499
−0.706
−0.030
1250
11487872

metaproterenol
18.94
0.116
0.450
−1.595
−1.153
0.539
0.339
−0.021
0.165
−0.393
1252
11467653

metaproterenol
20
0.206
0.018
−0.832
−1.005
2.154
0.212
0.086
0.138
−0.094
1252
11487912

citrinin
20
−0.040
0.637
−0.980
−0.590
0.122
0.012
0.608
0.730
0.218
1253
11488550

epicatechin
13.78
0.077
2.069
−1.037
−1.966
−0.231
0.446
−0.384
−0.419
−0.233
1254
11467790

catechin hydrate
13.78
0.165
1.848
−1.301
−1.926
0.880
1.085
−0.716
−0.596
−0.835
1254
11467965

cianidanol
20
0.630
1.283
−1.471
−1.746
−0.371
0.639
−0.113
−0.357
0.347
1254
11487983

aklomide
20
0.408
1.316
1.426
−0.447
0.061
0.510
0.378
0.594
−0.136
1255
11489327

sulfamethoxazole
15.8
0.057
1.529
−1.373
−0.894
1.190
0.332
−2.872
−3.540
−0.968
1256
11467325

sulfamethoxazole
20
−1.184
0.305
−1.108
−0.666
1.114
0.962
−0.491
−0.629
−0.140
1256
11488604

gallamine
7.84
0.266
−0.114
−0.712
−0.287
0.302
0.036
0.626
0.747
0.207
1257
11467305

gallamine
20
−1.064
−0.341
−1.683
−0.882
1.259
−0.492
0.057
−0.292
0.843
1257
11488894

pipemidic acid
13.18
−0.296
0.903
0.331
−0.613
0.743
0.101
0.006
−0.001
0.009
1258
11468045

pipemidic acid
20
−0.716
0.849
−0.367
−0.736
0.010
0.140
0.045
0.264
−0.333
1258
11489001

pyrimethamine
16.08
−0.974
−0.284
−1.597
−1.370
3.264
1.048
0.534
0.622
0.202
1259
11467185

pyrimethamine
20
0.994
0.449
−1.810
−0.696
0.329
−0.306
−0.657
−0.526
−0.825
1259
11488702

melphalan
20
−0.360
1.590
−1.387
0.151
−0.265
−0.954
1.449
1.282
1.453
1260
11487890

haloperidol
10.64
−0.724
0.613
−1.574
−0.350
0.415
−0.273
−0.735
−0.724
−0.641
1261
11467263

haloperidol
20
−0.814
−0.045
−0.795
0.733
0.915
0.465
−0.138
−0.072
−0.154
1261
11489084

tranexamic acid
25.44
0.823
0.745
−0.832
−0.479
0.254
−0.023
−0.165
0.003
−0.511
1262
11467319

tranexamic acid
20
−0.812
0.791
−0.710
−0.427
0.053
0.797
0.439
0.336
0.548
1262
11488471

artemisinin
14.16
0.529
−0.511
−0.505
−1.117
1.177
0.522
0.282
0.354
0.087
1263
11467646

artemisinin
20
0.336
0.737
0.616
−0.832
0.123
1.104
0.704
0.537
0.903
1263
11489328

salicyl alcohol
20
0.377
0.113
−0.178
−0.590
0.479
0.424
−0.486
−0.433
−0.498
1264
11489127

dicloxacillin sodium salt
8.5
−0.036
0.270
−0.883
−0.055
0.390
0.836
−0.206
0.009
−0.612
1265
11467598

dicloxacillin sodium
20
−0.214
−0.299
−0.587
0.196
−0.070
−1.277
0.661
0.533
0.870
1265
11488797

oxolinic acid
15.32
−0.516
0.455
−2.028
−0.445
1.339
0.227
−0.933
−1.010
−0.639
1266
11467341

oxolinic acid
20
−0.913
0.276
−1.598
−0.640
0.681
0.083
0.217
0.211
0.171
1266
11488749

acetaminophen
26.46
−0.635
0.239
−0.948
−0.670
0.917
0.803
−0.036
−0.177
0.259
1267
11468016

acetaminophen
20
−0.550
−0.283
−1.264
0.682
0.527
0.248
0.104
−0.038
0.317
1267
11487901

isoxicam
11.92
−0.403
−0.088
−1.505
−0.548
1.145
0.177
−0.744
−0.885
−0.352
1268
11467192

isoxicam
20
0.010
0.708
−0.152
−1.091
0.030
−0.169
−0.423
−0.221
−0.770
1268
11488678

spaglumic acid
13.14
0.790
1.145
−0.089
0.160
−0.046
0.600
1.074
0.963
1.087
1269
11468239

spaglumic acid
20
−0.009
0.357
−0.779
−0.685
0.615
0.191
0.120
0.307
−0.284
1269
11489387

hexamethonium bromide
19.76
−0.994
−0.586
−1.279
−1.259
3.128
−0.284
0.227
0.294
0.025
1270
11467186

hexamethonium bromide
20
−0.378
0.695
−1.179
−0.602
0.176
0.087
−0.735
−0.806
−0.442
1270
11489368

acetylcarnitine
20
−0.980
0.681
−1.275
−0.930
0.476
−0.192
−1.051
−1.015
−0.943
1271
11488742

clotrimazole
11.6
0.128
0.247
−0.610
−1.216
2.043
0.262
−0.278
−0.386
−0.006
1272
11467415

clotrimazole
20
0.099
−1.954
−2.182
−1.661
2.521
0.531
0.449
−0.106
1.434
1272
11487944

prednisone
20
−0.474
0.376
−1.054
0.258
0.253
−0.034
−0.290
−0.177
−0.473
1273
11489108

levamisole
19.58
0.266
1.515
−1.556
−0.266
0.798
−0.129
−0.076
−0.060
−0.144
1274
11467330

levamisole
20
−0.266
0.100
−0.340
−0.603
0.391
0.166
1.521
1.641
0.961
1274
11488681

carbenoxolone
7
−0.737
−0.425
−1.173
−0.878
1.614
0.145
0.074
0.071
0.063
1276
11467985

lanatoside C
20
−0.704
0.349
−0.887
−1.105
−0.033
0.664
−0.931
−0.844
−0.935
1277
11489268

diosmin
20
−0.712
0.452
−0.708
−0.501
0.321
−0.433
−1.223
−1.150
−1.147
1278
11488674

N-(2-aminoethyl)-4-chlorobenzamide
20
−1.090
0.830
−0.669
−1.051
1.036
−0.423
0.065
0.175
−0.205
1280
11489784

chlorothiazide
13.52
−0.647
1.522
−0.649
−0.130
0.110
0.431
−0.059
0.057
−0.267
1282
11467399

chlorothiazide
20
0.116
0.445
−0.711
−0.831
1.202
0.566
−0.331
−0.608
0.221
1282
11487970

calcein
20
5.567
2.057
−0.243
−3.437
11.668
0.465
−0.625
−0.468
−0.829
1284
11489179

methyl benzethonium chloride
9.38
−2.690
−3.432
−4.304
0.480
−1.501
−4.134
−0.165
−0.411
0.369
1286
11467853

methylbenzethonium
20
−4.580
−4.939
−5.614
−4.202
−3.108
−1.750
−1.868
−2.103
−1.043
1286
11489360

aklavine
20
−2.971
−8.498
−6.213
−3.626
−2.347
−5.658
0.706
0.430
1.063
1288
11487895

prednisolone
20
1.018
0.134
0.031
1.121
0.248
−1.111
−0.042
−0.155
0.191
1289
11489106

halazone
20
−0.242
−0.116
−0.445
−0.334
0.779
−0.942
0.565
0.593
0.385
1290
11488486

proglumide
11.96
0.138
−0.867
−0.599
−0.312
0.068
−0.001
−0.513
−0.787
0.094
1291
11467388

proglumide
20
−0.750
1.059
−1.254
−0.910
2.083
−0.033
−0.541
−0.394
−0.730
1291
11489222

allopurinol
20
0.376
1.218
−1.611
−0.204
1.448
−0.105
−0.869
−0.849
−0.798
1292
11487914

acetylcholine
20
−0.299
−0.013
−0.712
−0.520
0.622
−0.038
0.358
0.533
0.014
1293
11489074

amodiaquine
20
−0.547
−0.270
−1.008
−1.178
0.877
−0.008
0.398
0.317
0.481
1294
11488584

chlorambucil
13.14
−0.507
−0.010
−0.069
0.199
0.056
0.035
0.249
0.147
0.398
1295
11468227

chlorambucil
20
−0.007
0.189
−1.519
−0.826
0.165
−0.955
0.725
0.360
1.273
1295
11487881

eugenol
20
−0.943
0.081
−0.243
−0.816
1.068
0.307
−0.254
−0.166
−0.320
1297
11489080

nimesulide
12.98
−0.822
−0.018
−1.583
−0.754
1.468
0.400
−1.217
−1.237
−0.978
1298
11467342

nimesulide
20
0.614
0.567
−0.534
−0.731
1.174
0.089
−0.661
−0.775
−0.313
1298
11489357

aminohippuric acid
20.6
−0.266
0.957
−0.126
−0.343
0.426
0.320
0.568
0.976
−0.395
1299
11468043

aminohippuric acid
20
0.597
0.226
−0.983
−0.606
−0.310
0.243
0.220
0.160
0.304
1299
11489331

dipyridamole
7.92
2.069
1.296
−0.034
0.298
−0.282
0.377
−0.352
−0.128
−0.777
1301
11467290

dipyridamole
20
1.042
0.127
−0.606
0.474
0.044
0.276
−0.245
−0.314
0.010
1301
11488788

bromocriptine
20
1.142
0.331
−1.667
0.037
0.176
−0.064
0.006
0.199
−0.322
1302
11488940

clidinium
11.34
0.172
0.127
−2.250
−0.715
1.870
0.176
−0.462
−0.202
−0.903
1303
11467970

clidinium
20
−0.084
−0.723
−1.393
−0.772
1.625
−0.062
−0.556
−0.503
−0.602
1303
11487940

endrin
20
0.522
0.305
−1.710
0.129
0.770
0.726
−0.680
−0.738
−0.385
1304
11489682

quinine ethyl carbonate
20
−0.167
0.317
−0.071
−0.661
0.401
0.822
−1.190
−1.003
−1.297
1305
11489729

mitotane
20
−1.631
0.341
−1.708
−0.542
0.460
−0.216
−0.030
0.072
−0.244
1307
11488732

ciclopirox ethanolamine
19.3
0.101
−1.563
−2.239
2.994
−1.968
−0.351
−0.888
−0.577
−1.343
1309
11467689

ciclopirox olamine
20
−1.409
−1.900
−3.390
2.355
−1.545
−0.381
−0.965
−1.098
−0.569
1309
11487962

sodium beta-nicotinamide adenine dinucleotide phosphate
20
−0.562
0.550
−1.286
−0.582
−0.038
0.101
−0.424
−0.307
−0.615
1310
11487839

cacodylic acid
20
−1.224
0.283
−0.720
0.227
0.527
−0.903
−0.597
−0.504
−0.587
1312
11488986

niclosamide
12.22
−1.410
−6.135
−3.816
−3.700
−3.069
−3.177
−0.976
−1.007
−0.755
1313
11467188

niclosamide
20
−0.944
−6.076
−0.296
−4.256
−3.862
−2.947
−1.042
−0.288
−2.299
1313
11488999

quinapril
20
0.034
0.434
−1.111
−0.276
1.175
0.237
−0.132
−0.127
−0.130
1314
11488641

hesperidin
20
0.694
0.769
−0.992
−0.251
−0.281
0.621
−0.618
−0.106
−1.561
1315
11488619

tulobuterol
20
−0.239
−0.653
−0.706
−1.186
0.569
0.326
−0.101
−0.257
0.258
1316
11489432

flutrimazole
20
0.858
0.176
−0.356
−0.429
0.781
0.904
−0.763
−0.592
−0.915
1317
11489422

oxethazaine
8.56
−0.497
−1.284
−1.374
−0.742
1.092
−0.550
0.473
0.335
0.609
1318
11467206

oxethazaine
20
−0.294
−0.217
−1.451
0.173
−0.055
−0.278
−0.739
−0.812
−0.486
1318
11489803

putrescine
20
−0.586
1.023
−0.806
−0.888
0.279
0.897
−0.341
−0.160
−0.684
1319
11489751

methylthiouracil
20
−0.235
0.145
−0.633
−0.553
0.815
0.846
−0.029
0.146
−0.302
1321
11489092

scopoletin
20.82
0.413
1.951
0.261
0.146
−0.017
0.501
−0.462
−0.513
−0.291
1322
11468110

scopoletin
20
0.675
2.444
−0.957
−0.056
0.727
0.928
0.543
0.746
0.101
1322
11489023

ofloxacin
11.06
−0.425
−0.350
−0.967
−0.891
0.908
0.492
0.182
0.059
0.353
1323
11467385

ofloxacin
20
−1.148
1.339
−1.248
−0.281
−0.182
0.309
−0.458
−0.622
−0.041
1323
11489280

alexidine
7.86
−4.805
−5.106
−5.432
−3.726
−4.270
−3.201
−1.696
−1.387
−2.011
1324
11467925

alexidine
20
−2.974
−1.715
−2.693
−1.139
−0.298
−3.981
−0.288
−0.289
−0.150
1324
11488915

cycloleucine
20
−1.300
0.045
−1.310
−0.765
0.024
0.822
−0.839
−0.495
−1.397
1325
11488747

1r-camphor
20
−0.744
0.270
−0.402
−0.794
0.042
0.372
0.073
0.107
0.023
1326
11488199

carbachol
27.18
−0.239
−1.509
0.905
−0.296
1.223
−0.202
−0.060
−0.176
0.191
1327
11468028

carbachol
20
−0.502
−0.772
−1.002
−0.965
1.304
−0.154
0.355
0.273
0.391
1327
11487930

trichlormethine
20
−0.518
−0.063
−0.632
0.122
−0.166
−0.075
0.575
0.436
0.723
1330
11488596

pentoxifylline
14.38
−1.056
0.512
−2.051
−0.753
1.324
0.568
−0.828
−0.817
−0.725
1331
11467344

pentoxifylline
20
0.375
−0.027
−0.600
−0.696
0.182
−0.798
0.062
0.292
−0.344
1331
11488997

chlorthalidone
11.8
0.081
0.147
−1.736
−0.750
1.047
0.531
−0.236
−0.009
−0.641
1332
11467499

chlorthalidone
20
0.308
0.323
−1.134
−0.257
1.655
0.066
0.793
0.646
0.877
1332
11487915

polymyxin b sulfate
20
0.819
1.157
−0.522
0.738
0.342
−0.323
−0.382
−0.349
−0.341
1333
11488306

dexamethasone
20
−0.614
0.457
−1.038
0.273
0.021
0.032
−0.901
−0.915
−0.718
1334
11488640

carbenicillin
20
−0.524
0.037
−0.565
0.298
2.042
−0.074
−0.869
−0.835
−0.823
1336
11487936

cloxacillin
9.18
−0.639
−0.258
−1.268
−0.547
1.697
0.381
−0.901
−0.799
−0.974
1337
11467334

cloxacillin
20
−0.395
0.231
−1.769
−0.339
0.259
0.459
−0.568
−0.506
−0.508
1337
11488959

proadifen
11.32
−0.388
−0.746
−1.220
−0.557
0.616
0.223
−0.364
−0.414
−0.201
1338
11467926

proadifen
20
−1.715
−0.702
−1.808
−0.654
0.678
−0.077
−0.377
−0.243
−0.595
1338
11488740

tiapride
12.18
−1.454
0.231
−1.563
−0.800
0.653
0.917
0.341
0.416
0.086
1339
11467364

tiapride
20
1.174
0.797
−0.646
0.171
−0.466
−0.107
−0.283
−0.220
−0.355
1339
11489337

triacetin
20
−0.842
−0.008
−0.717
−0.571
0.431
−0.264
−0.327
−0.187
−0.569
1341
11488755

thiram
20
−5.812
−8.121
−6.222
−4.011
−3.915
−4.853
−2.420
−2.770
−1.220
1342
11489370

quassin
20
−0.688
0.866
−0.400
0.033
0.925
−0.233
0.095
0.205
−0.168
1343
11488532

hydrocortisone butyrate
20
−1.654
−0.353
−0.932
−0.808
1.234
−0.064
0.666
0.514
0.916
1344
11488922

mefexamide
14.26
−0.541
−0.271
−1.363
−0.719
1.172
0.129
−0.340
−0.498
0.009
1346
11467363

mefexamide
20
−2.120
−0.606
−1.270
−0.643
0.837
−0.257
−0.215
−0.253
−0.101
1346
11489215

fipexide
10.28
−0.617
−0.148
−0.924
−0.624
0.307
0.573
0.169
0.163
0.155
1348
11467446

fipexide
20
0.721
−0.397
−0.186
−0.354
0.873
−0.071
−0.241
−0.010
−0.657
1348
11489354

mebendazole
13.54
0.064
0.344
−2.797
−0.054
−0.791
−0.685
0.013
−0.200
0.398
1350
11467365

mebendazole
20
0.512
−0.483
−2.060
−0.434
−1.003
−1.473
1.160
1.212
0.824
1350
11489217

dequalinium
8.76
−3.696
−5.078
−5.151
−3.242
−3.041
−4.108
−1.322
−0.852
−2.024
1351
11467536

dequalinium
20
−3.176
−5.120
−4.446
−2.506
−3.055
−3.241
−1.733
−1.087
−2.705
1351
11488466

colchicine
10.02
−0.197
−0.451
−3.253
−1.055
−0.345
−0.642
0.551
0.807
−0.072
1352
11467511

colchicine
20
0.571
0.011
−2.566
−0.237
−0.377
−1.079
1.293
1.549
0.472
1352
11487891

vulpinic acid
20
−1.120
0.685
0.403
−3.484
1.407
1.037
−0.152
0.168
−0.792
1353
11488613

picrotin
20
−0.278
0.205
−1.155
−0.167
0.917
0.184
0.253
0.404
−0.167
1355
11488095

oxyquinoline
20
−1.140
0.574
−0.815
−0.867
0.684
−0.121
0.534
0.526
0.435
1356
11488513

bupivacaine
13.86
−0.663
−0.329
−1.440
−0.938
0.545
−0.058
−0.227
−0.316
0.002
1357
11467453

bupivacaine
20
−1.202
−1.058
−0.841
0.084
0.801
0.190
0.392
0.548
0.009
1357
11489405

mechlorethamine
20
−4.522
−7.662
−5.914
−3.054
−1.607
−4.774
0.791
−0.193
2.727
1358
11488264

chlorhexidine
7.92
−1.859
−2.238
−4.138
0.348
−2.490
0.090
0.775
0.990
0.140
1360
11467291

chlorhexidine
20
−0.976
−1.078
−2.340
0.412
1.660
−1.683
−0.455
−0.592
−0.141
1360
11487951

methoxy-8-psoralen
18.5
1.463
−0.070
−0.371
0.605
0.103
0.227
0.803
0.952
0.340
1362
11467627

methoxsalen
20
0.416
0.776
−0.976
−0.034
0.310
−0.889
−0.562
−0.513
−0.489
1362
11488868

erythromycin ethylsuccinate
20
−0.945
0.825
−1.100
−0.488
0.555
0.220
−0.390
−0.433
−0.163
1363
11488799

alpha-cyano-3-hydroxycinnamic acid
20
−0.861
−0.225
−0.323
−0.165
0.452
0.349
−0.747
−0.903
−0.285
1364
11489287

amitriptyline
14.42
−1.086
−1.116
−1.566
−0.712
1.177
−1.338
−0.898
−0.914
−0.743
1365
11467222

amitriptyline
20
−0.040
−1.393
−1.785
0.136
−0.471
0.013
−0.903
−0.890
−0.807
1365
11487917

chlorocresol
20
−0.414
−0.105
−0.607
0.528
0.102
0.747
0.206
0.611
−0.728
1367
11487818

bacitracin
20
−0.312
0.131
−0.826
−0.113
1.177
0.305
1.271
1.374
0.798
1368
11488555

dienestrol
15.02
0.829
−0.794
−0.652
−0.205
−0.210
0.894
0.033
−0.191
0.481
1370
11467946

dienestrol
20
0.290
0.336
−0.326
0.129
−0.260
−0.653
−0.280
−0.251
−0.222
1370
11488787

altretamine
19.02
−0.533
−0.294
−0.442
−0.440
0.462
0.040
0.884
0.750
0.972
1371
11468094

altretamine
20
−0.315
0.427
−1.416
−0.322
0.103
−0.631
0.379
0.488
0.069
1371
11488723

quinolinic acid
20
−0.516
0.107
−1.118
−1.023
0.849
−0.222
−0.586
−0.575
−0.519
1372
11488745

benzethonium
9.7
−3.952
−4.769
−4.836
−0.956
−1.431
−3.642
−0.549
−0.892
0.252
1373
11467856

benzethonium
20
−3.709
−5.713
−5.088
−3.825
−1.610
−2.507
−2.587
−2.402
−2.525
1373
11487950

broxyquinoline
20
−2.006
−1.237
−1.180
1.701
−1.081
0.410
−0.830
−1.095
−0.157
1374
11488760

penicillin V
20
0.062
0.818
−1.319
−0.564
0.748
0.258
−0.849
−0.844
−0.654
1377
11488311

dopamine
20
−0.964
0.276
−0.754
−0.849
−0.046
0.007
−0.337
−0.112
−0.655
1378
11488839

potassium p-aminobenzoate
20
−0.277
−0.299
−1.445
−0.826
0.818
0.519
−1.001
−1.085
−0.673
1381
11487939

salinomycin
20
−0.247
−3.542
−2.918
2.976
−3.111
−0.566
−1.400
−0.345
−3.359
1383
11487889

clopidogrel
20
−1.134
1.367
−1.447
−0.698
−0.196
0.410
−1.470
−1.328
−1.441
1384
11488328

cinnarazine
20
0.752
0.694
−1.003
0.544
0.777
0.758
−0.648
−0.541
−0.742
1385
11489347

nomifensin
16.78
0.121
1.748
−0.534
−0.329
3.133
−1.298
−0.331
−0.571
0.181
1386
11467256

nomifensin
20
0.525
1.604
−0.885
−0.059
3.112
−1.233
−0.131
−0.169
−0.026
1386
11489364

mefloquine
10.58
−0.183
−0.789
−1.368
−0.537
−0.069
0.498
−0.036
−0.073
0.007
1387
11467274

mefloquine
20
1.135
0.104
0.374
−0.505
−0.983
−1.496
0.362
0.552
−0.093
1387
11489332

loratadine
20
0.552
0.033
−1.609
0.191
0.764
−0.317
−0.306
−0.182
−0.499
1389
11489400

clenbuterol
14.44
0.134
−0.416
−1.330
−1.139
0.914
−0.261
0.054
0.063
0.011
1390
11467493

clomipramine
12.7
0.325
0.119
−0.916
−0.664
0.309
−1.110
0.513
0.663
0.109
1393
11467417

clomipramine
20
−0.924
−1.580
−0.508
0.121
0.466
−0.084
−0.808
−0.776
−0.679
1393
11489545

pipobroman
20
−0.792
−0.161
−1.907
−0.580
0.342
0.441
−1.074
−0.918
−1.219
1394
11488728

phenoxybenzamine
13.16
−0.751
0.878
−0.159
−0.422
0.444
−0.470
−0.155
−0.306
0.167
1395
11468092

phenoxybenzamine
20
−0.906
0.340
−1.049
0.021
0.256
−0.188
−1.302
−1.077
−1.462
1395
11489631

chloroxylenol
20
−0.639
−1.134
−2.046
−0.917
2.165
0.499
−0.811
−0.857
−0.614
1396
11487952

propantheline
10.86
−0.361
0.808
−1.670
−0.893
0.589
−0.615
−0.301
0.104
−1.055
1397
11467975

propantheline
20
0.142
0.070
−1.026
−0.082
2.062
0.379
0.458
0.254
0.783
1397
11489116

alpha-tochopheryl acetate
20
−0.957
0.293
−1.398
−0.734
0.364
0.261
0.212
0.339
−0.094
1398
11488559

ergocalciferol
20
0.372
−0.913
−1.658
−0.449
1.541
−0.118
0.661
0.723
0.357
1400
11487942

triflupromazine
11.36
−0.423
−0.564
−1.896
−0.417
1.208
−0.802
0.225
0.404
−0.230
1401
11467201

edrophonium
24.06
0.250
1.406
0.901
−0.161
0.343
0.177
−0.803
−0.611
−1.083
1402
11467231

edrophonium
20
−0.291
0.134
−0.015
0.391
1.006
1.045
−0.806
−1.001
−0.183
1402
11488926

arecoline
25.78
0.481
1.774
−0.607
−0.281
−1.084
0.503
0.098
0.385
−0.513
1403
11467550

arecoline
20
0.018
−0.361
−0.452
−0.451
−1.032
0.839
−0.545
−0.261
−1.072
1403
11487867

phenazopyridine
18.76
−0.413
−0.676
−2.094
0.126
0.587
0.678
−0.561
−0.323
−0.930
1404
11467900

phenazopyridine
20
0.627
0.077
−0.692
1.263
1.911
0.335
0.362
0.207
0.544
1404
11487833

equilin
14.9
−0.882
−0.045
−2.270
−0.408
0.259
−0.069
−0.626
−0.538
−0.676
1405
11467998

nitromide
20
−0.259
0.548
−1.071
1.648
1.299
−0.346
−0.128
−0.100
−0.086
1406
11488860

O-benzyl-L-serine
20
−0.140
1.374
0.176
−0.374
0.228
0.513
0.750
0.854
0.378
1407
11489167

adamantamine
26.44
0.544
2.278
−0.637
−1.007
−0.537
0.293
−0.051
0.110
−0.374
1408
11467555

amantadine
20
−0.755
0.261
−0.267
1.115
−0.239
0.758
−0.415
−0.421
−0.386
1408
11487897

carisoprodol
15.36
0.291
0.357
−1.027
−0.276
0.321
0.553
−0.293
0.040
−0.920
1409
11467571

carisoprodol
20
−0.444
0.373
−1.366
−0.597
0.185
0.256
−0.099
−0.072
−0.066
1409
11488969

thiotepa
20
−0.029
0.586
−1.879
0.010
0.678
−0.181
−0.262
−0.289
−0.156
1410
11489373

carbinoxamine
13.76
2.471
1.444
−0.685
−0.435
−0.603
0.034
−0.720
−0.795
−0.435
1412
11467949

carbinoxamine
20
0.299
1.215
−1.163
−0.287
−0.216
1.098
0.126
0.257
−0.095
1412
11488943

menthol
20
−0.489
−0.065
−0.673
−0.872
1.316
−0.074
−1.207
−1.028
−1.345
1413
11488671

acetohydroxamic acid
20
−0.102
−0.596
−1.547
−0.353
1.489
0.637
0.353
0.480
−0.031
1414
11487925

N-(3-trifluoromethylphenyl)piperazine
20
0.030
−0.069
−1.081
−0.280
0.211
−0.808
−0.244
−0.076
−0.538
1415
11489389

8-cyclopentyltheophylline
20
−0.704
−0.448
−1.776
−0.715
1.385
0.425
−1.051
−0.934
−1.039
1416
11489550

benzalkonium
20
−5.597
−8.103
−5.999
−4.220
−2.894
−5.374
−2.209
−2.811
−0.558
1417
11489382

tetracycline
9
−0.461
0.284
0.314
−1.031
0.987
−0.461
0.538
−0.066
1.642
1418
11467288

tetracycline
20
−0.405
−0.099
0.144
−0.854
0.275
−0.453
−0.307
−0.903
0.970
1418
11489145

cystamine
20
0.077
1.203
0.470
−0.542
0.154
0.575
−0.241
−0.229
−0.232
1419
11489407

bucladesine
20
0.404
0.685
0.236
0.081
−0.704
0.232
−0.193
−0.127
−0.293
1424
11489329

mexiletine
22.32
−1.055
0.883
−0.564
0.161
0.003
1.114
−0.622
−0.495
−0.746
1425
11467389

pindolol
16.1
1.151
0.582
0.527
−0.282
0.171
0.446
−0.179
−0.067
−0.414
1428
11467238

pindolol
20
−1.160
1.183
−1.010
0.284
0.584
−0.510
0.580
0.750
0.120
1428
11489101

butamben
20.7
0.465
−0.329
−1.413
−0.405
0.458
−1.345
0.249
0.462
−0.220
1429
11467909

butamben
20
−0.599
−0.280
−1.083
0.155
0.587
0.499
−0.168
−0.299
0.111
1429
11488666

beclomethasone
20
−1.221
0.138
−1.585
−0.124
−0.235
0.742
−0.363
−0.121
−0.717
1430
11488968

cloperastine
12.12
1.312
−0.362
−0.617
0.444
−0.058
−2.035
0.163
−0.055
0.565
1431
11467941

cloperastine
20
−1.911
−1.783
−2.310
1.329
−0.584
0.236
0.098
0.023
0.244
1431
11489412

doxylamine
14.8
−0.205
−0.615
−0.786
−0.987
1.374
0.376
0.608
0.733
0.189
1432
11467175

doxylamine
20
−0.540
−0.432
−1.702
−0.607
0.824
0.403
1.206
1.249
0.832
1432
11487931

thiamphenicol
11.22
−1.067
0.539
−1.142
−1.450
1.069
−0.244
0.379
−0.128
1.288
1433
11467173

thiamphenicol
20
−0.141
1.214
−0.592
−1.738
0.259
0.684
−0.184
−0.555
0.576
1433
11488672

mianserine
15.14
0.046
−0.121
0.311
−1.027
0.821
0.473
0.177
0.196
0.064
1434
11467247

mianserin
20
1.265
2.340
−0.571
0.032
−0.195
0.027
−2.484
−2.139
−2.627
1434
11489019

prilocaine
18.16
−0.849
0.292
−0.942
−1.028
1.264
0.451
−0.114
−0.250
0.147
1436
11467347

prilocaine
20
−0.199
0.692
−1.488
−0.236
1.108
−0.128
−0.510
−0.380
−0.660
1436
11489365

busulfan
20
−0.872
−0.512
−1.724
−0.640
0.750
−0.091
−0.521
−0.589
−0.351
1437
11487883

fenoprofen
16.52
−1.127
−0.273
−2.117
−0.883
0.643
0.630
−0.069
0.089
−0.378
1438
11467902

fenoprofen
20
0.208
0.310
−0.901
−0.574
0.466
0.615
−0.299
−0.193
−0.458
1438
11489207

methionyl-leucylphenylalanine
20
0.092
0.113
−0.588
−0.520
−0.238
0.307
−0.566
−0.494
−0.548
1439
11488338

nabumetone
17.52
1.588
−0.738
0.192
−0.258
−0.321
−0.220
0.861
0.735
0.950
1440
11468057

nabumetone
20
0.467
−0.618
−0.708
−0.551
0.637
0.002
−0.574
−0.655
−0.331
1440
11489785

diphenylpyraline
14.22
−0.989
−0.041
−1.315
−0.876
1.563
0.321
−0.149
−0.125
−0.157
1441
11467855

diphenylpyraline
20
−0.669
−0.242
−1.169
−0.754
0.224
0.558
0.019
0.157
−0.196
1441
11488798

citiolone
20
0.835
1.581
−0.973
−0.561
0.172
0.781
0.272
0.477
−0.203
1442
11489348

orphenadrine
14.84
−0.069
−0.863
0.082
−0.402
1.010
−0.764
−0.143
−0.491
0.548
1443
11467387

orphenadrine
20
0.128
−0.073
−0.675
−0.712
1.018
0.090
0.605
0.655
0.453
1443
11488854

tetrahydrozoline
19.98
−0.895
−1.172
−1.638
−0.912
1.093
−0.635
−0.209
−0.275
−0.038
1444
11467846

tetrahydrozoline
20
−0.613
−0.208
−0.804
−0.172
0.334
0.250
0.144
0.168
0.073
1444
11489146

veratrine
20
−0.110
−0.519
−1.983
−0.605
1.771
0.166
0.710
0.440
1.068
1445
11487954

cevadine
20
−0.774
1.682
0.154
0.976
0.811
0.751
−0.061
−0.197
0.270
1445
11488225

cromolyn
8.54
0.234
0.485
−1.485
−0.558
1.343
−0.227
−0.015
0.163
−0.379
1446
11467960

cromolyn
20
−0.052
0.255
−0.892
−0.444
0.231
0.869
−0.251
−0.309
−0.008
1446
11488953

salicylamide
20
−1.007
−0.150
−1.355
−0.463
0.005
0.508
−0.736
−0.669
−0.742
1447
11489128

sulfasalazine
10.04
−1.107
−0.490
−0.392
−0.688
0.782
0.073
−0.230
−0.080
−0.487
1448
11467668

sulfasalazine
20
−0.153
1.270
−1.245
−0.834
1.165
−0.230
−0.495
−0.477
−0.365
1448
11489032

(−)-cotinine
22.7
0.390
2.001
−0.864
−0.172
−0.622
0.628
0.395
0.540
−0.026
1449
11467230

tryptamine
20
0.186
1.142
0.144
−0.190
−0.902
0.265
−0.253
−0.133
−0.479
1450
11488689

demeclocycline
8.6
−0.733
−0.208
−2.363
−1.613
0.110
0.583
−0.419
−0.596
0.029
1451
11467901

demeclocycline
20
0.335
−0.475
−0.417
−0.818
0.335
0.288
0.257
0.051
0.687
1451
11488948

butacaine
13.06
0.068
0.171
−1.779
−0.803
1.431
1.442
−0.782
−0.628
−0.942
1452
11467979

butacaine
20
−0.314
1.044
1.041
−0.643
0.851
0.853
−0.035
0.096
−0.289
1452
11489409

morantel
20
−0.771
−0.407
0.409
−0.462
0.854
0.336
−0.298
−0.433
0.043
1453
11489415

digoxin
20
−0.496
0.763
−0.712
−0.649
0.811
0.445
0.055
0.352
−0.478
1454
11489078

prednisolone acetate
20
−0.718
0.779
−0.849
0.408
−0.427
0.542
−0.663
−0.647
−0.577
1455
11489107

amcinonide
20
−1.374
−0.809
−0.832
0.024
−0.029
−0.388
0.347
0.218
0.553
1457
11489404

p-chlorophenylalanine
20
−0.693
−0.481
−0.682
0.132
0.459
−0.836
−0.912
−0.932
−0.693
1458
11489295

periciazine
20
−0.660
1.176
−0.926
0.103
0.438
0.380
−0.073
0.127
−0.431
1459
11489420

oxyphencyclimine
20
−0.350
−0.530
0.758
−0.078
0.273
−0.467
−0.445
−0.471
−0.298
1461
11489416

eucatropine
20
−0.370
0.786
−1.051
−0.460
0.779
−0.178
−0.784
−0.829
−0.468
1462
11488840

acacetin
14.08
−0.644
−0.392
−1.686
−0.249
0.407
0.284
−0.125
−0.153
−0.031
1463
11467843

perphenazine
9.9
−0.669
−0.649
−1.350
0.363
0.220
−5.391
−3.078
−3.105
−2.462
1465
11467273

perphenazine
20
−5.616
−8.464
−6.728
−3.919
−2.181
−1.097
−1.879
−4.321
3.415
1465
11489418

pramoxine
13.64
−0.472
0.272
−0.996
−0.786
1.252
0.281
−0.417
−0.312
−0.553
1467
11467864

pramoxine
20
0.281
−0.351
0.408
0.784
1.645
1.272
−0.384
−0.464
−0.213
1467
11487846

estradiol valerate
20
−0.004
1.049
−1.328
−0.438
0.024
0.511
−0.247
−0.319
0.017
1468
11488789

para-aminoglutethimide
17.22
−1.894
2.546
−0.986
−0.416
0.462
0.101
−0.273
−0.068
−0.631
1469
11467392

aminoglutethimide
20
−0.567
0.702
−1.626
−0.414
0.643
0.832
−0.932
−1.079
−0.505
1469
11487909

d[-arg-2]kyotorphan acetate
20
−0.130
−0.165
−0.797
−0.763
0.435
−0.278
−0.327
−0.304
−0.262
1470
11488365

chlormezanone
14.62
0.263
0.644
−1.097
−0.954
1.905
−0.393
0.013
0.271
−0.501
1471
11467484

chlormezanone
20
−0.982
1.028
−0.816
−0.656
0.376
0.366
−0.904
−0.934
−0.621
1471
11489623

S-(+)-ibuprofen
19.4
−0.372
0.087
0.383
−0.423
0.394
0.056
−0.090
−0.188
0.114
1472
11468055

enoxolone
20
−2.187
−0.994
−1.993
−1.187
0.093
−1.053
−0.061
−0.265
0.420
1473
11488280

cisplatin
20
0.096
1.546
−0.436
−0.211
1.080
−0.018
−1.012
−0.963
−0.932
1475
11488715

maprotiline
14.42
−0.127
−0.733
−2.004
−0.689
0.689
−3.786
0.189
0.168
0.192
1476
11467494

maprotiline
20
−3.819
−6.642
−3.986
2.189
−1.099
−0.559
−0.506
−0.665
−0.146
1476
11487955

carboplatin
20
0.649
0.654
−1.486
0.094
1.451
0.594
0.053
0.165
−0.217
1477
11488714

celecoxib
20
0.351
0.274
−1.656
−0.672
0.658
−0.042
−0.202
−0.178
−0.212
1478
11489392

(−)-isoproterenol
18.94
0.087
0.181
−0.723
−1.028
−0.331
0.363
−0.200
−0.128
−0.316
1479
11468245

isoproterenol
20
0.730
0.168
−0.882
−0.779
0.605
−0.801
0.262
0.386
0.017
1479
11488877

chlorzoxazone
23.58
0.774
2.443
−0.611
−0.272
−0.121
−0.145
−1.678
−1.598
−1.554
1480
11467311

chlorzoxazone
20
−0.501
0.017
−0.785
0.156
0.101
0.869
−0.150
−0.008
−0.327
1480
11488965

dicumarol
11.9
0.172
−0.207
1.467
−1.176
0.459
0.667
0.083
0.097
0.040
1481
11467933

dicumarol
20
−0.920
−0.578
0.942
−1.580
1.278
−0.303
−0.134
−0.240
0.043
1481
11487960

hydrastinine
19.3
−1.121
0.204
−1.069
−0.613
1.251
0.936
−0.846
−0.941
−0.521
1482
11467343

hydrastinine
20
−0.659
−0.066
−0.492
−0.480
1.192
0.115
0.058
0.044
0.052
1482
11488558

ethacrynic acid
13.2
−0.069
1.674
−0.744
−0.682
0.089
−0.033
−0.036
0.149
−0.403
1485
11467407

ethacrynic acid
20
0.284
1.296
−0.997
−0.505
0.061
0.129
0.505
0.998
−0.638
1485
11487913

practolol
15.02
0.251
1.735
−0.117
−0.473
0.732
0.038
−0.600
−0.494
−0.698
1486
11467480

practolol
20
−0.031
0.132
−1.098
−1.018
0.234
0.424
0.087
0.203
−0.164
1486
11489388

iopanoic acid
7
0.265
0.322
−0.551
−0.198
0.019
0.294
−1.601
−1.415
−1.687
1487
11468200

iopanic acid
20
0.374
1.094
−0.784
−0.025
0.025
0.503
0.027
0.023
0.113
1487
11489022

propafenone
11.72
0.606
0.478
−1.005
−0.247
0.684
−0.486
0.062
0.170
−0.167
1489
11467647

propafenone
20
−0.412
−1.777
−1.869
0.754
−0.397
0.385
−0.333
−0.158
−0.584
1489
11489419

clobetasol
20
−0.819
−0.048
0.167
0.247
0.083
0.087
−0.276
−0.209
−0.346
1493
11489410

quipazine
18.76
−0.544
−0.866
−1.353
−0.877
0.634
0.445
−0.271
−0.186
−0.385
1494
11467765

quipazine
20
0.646
−1.077
−0.264
−0.143
−0.670
−0.072
−0.334
−0.227
−0.423
1494
11488998

thioctic acid
20
0.440
1.725
0.035
−0.534
0.002
0.758
0.258
0.423
−0.104
1495
11489421

methiothepin
11.22
−0.990
−0.955
−1.614
−0.409
1.188
−3.974
−0.262
−0.159
−0.427
1496
11467523

methiothepin
20
−2.027
−5.584
−3.763
1.341
−0.285
−1.216
−0.086
−0.375
0.475
1496
11489783

foscarnet
20
−0.207
1.127
−0.681
−0.158
0.437
−2.013
−1.257
−1.184
−1.178
1498
11488484

leflunomide
14.8
−0.145
−0.678
−0.758
−0.317
0.744
0.293
−0.697
−0.329
−1.303
1499
11467920

tyramine
20
−0.048
0.109
−0.760
−0.170
1.977
0.316
−0.493
−0.679
−0.038
1501
11488554

lansoprazole
10.82
−0.710
0.403
−0.974
−0.117
0.243
0.264
−1.144
−1.071
−1.089
1503
11468220

lansoprazole
20
−0.829
0.866
−1.210
−0.539
0.862
0.372
−0.954
−0.942
−0.755
1503
11488260

buspirone
10.38
−0.642
0.084
−0.306
−0.555
1.384
0.228
−0.237
−0.130
−0.411
1504
11467517

isobutylmethylxanthine
20
−1.003
−0.512
−1.388
−1.195
1.347
−0.320
0.023
0.064
−0.024
1505
11489551

kojic acid
20
0.022
−0.307
−0.583
−0.698
0.452
−0.170
−1.176
−1.166
−0.914
1506
11489644

heptaminol
27.54
−0.287
0.919
−1.086
−0.701
1.049
0.515
0.814
0.951
0.334
1507
11467163

heptaminol
20
−0.057
0.764
−1.067
−0.723
0.571
−0.049
−0.838
−0.743
−0.880
1507
11489352

N-formylmethionylalanine
20
0.189
0.518
−1.235
0.069
1.037
0.200
0.600
0.647
0.462
1508
11488876

ronidazole
19.98
−0.232
−0.358
−0.118
0.050
−0.309
−0.232
0.352
0.460
0.051
1509
11468263

ronidazole
20
−0.379
1.734
−0.413
−0.452
1.160
−0.017
−0.220
−0.159
−0.229
1509
11488853

methapyrilene
15.3
0.186
−0.116
−1.192
−0.775
0.798
−0.022
0.110
0.100
0.101
1510
11467490

methapyrilene
20
−0.409
−0.039
−1.213
−0.638
1.114
0.413
0.426
0.400
0.356
1510
11489802

phenolphthalein
20
−0.278
−1.699
−2.400
−1.090
−0.942
−2.351
0.932
0.671
1.341
1511
11489095

pronethalol
17.44
−0.005
1.102
−0.566
−0.600
0.951
−0.239
−0.038
0.090
−0.309
1512
11468122

pronetalol
20
0.173
−0.128
0.091
−0.325
0.758
0.559
−0.573
−0.592
−0.427
1512
11489386

benzocaine
24.22
−1.335
−0.085
−1.492
−0.788
0.998
0.490
0.227
0.141
0.358
1513
11467860

benzocaine
20
−0.252
−0.632
−2.225
−0.534
1.361
0.099
0.299
0.215
0.345
1513
11487933

fosfomycin
20
−0.499
0.611
−1.058
−0.679
0.789
−0.407
−0.210
−0.185
−0.245
1514
11488502

tacrine
20.18
−0.621
1.500
−0.730
−0.639
0.880
−0.250
−0.039
−0.020
−0.079
1516
11467477

aminacrine
20
−1.222
1.719
−1.273
−0.517
0.686
0.340
0.883
1.309
−0.097
1516
11488928

9-amino-1,2,3,4-tetrahydroacridine
20
0.348
−0.633
−1.045
−1.032
0.240
0.967
−0.946
−0.736
−1.154
1516
11489628

mephenytoin
18.32
0.032
−0.688
−0.090
−0.115
−0.081
−0.461
0.471
0.285
0.757
1517
11468256

diflunisal
15.98
−2.269
−0.477
−0.998
−0.194
1.159
0.255
−0.541
−0.378
−0.797
1518
11467187

diflunisal
20
−0.137
−0.283
−1.398
−0.690
−0.211
0.174
−0.195
0.056
−0.599
1518
11488828

dimethadione
30.98
−0.300
0.012
−1.204
−0.494
1.532
−1.458
−0.735
−0.571
−0.929
1519
11467977

dimethadione
20
0.829
0.249
−0.537
0.206
0.933
0.572
−0.276
−0.186
−0.459
1519
11487924

hamidium
20
−3.449
−6.380
−4.647
−2.831
−1.903
−2.061
−2.145
−0.555
−4.967
1520
11489403

hydroxychloroquine
20
−0.578
−0.057
−1.295
−0.692
1.276
−0.214
0.033
−0.008
0.194
1522
11489054

salbutamol
16.72
−1.273
−0.806
−1.380
−0.648
1.008
−1.464
0.581
0.539
0.508
1523
11467346

albuterol
20
−0.495
0.505
−0.573
−0.319
0.938
−0.191
0.783
0.558
1.116
1523
11489166

isopyrin
16.3
0.412
1.307
−0.704
−0.743
−1.749
0.254
0.093
0.153
−0.053
1524
11467870

ramifenazone
20
−0.444
0.456
−0.091
−0.668
−0.730
1.006
0.468
0.538
0.230
1524
11489408

clopamide
11.56
−2.152
0.299
−1.129
−0.726
0.878
−0.184
−0.075
0.110
−0.440
1526
11467502

clopamide
20
−0.562
0.929
−0.901
−0.617
0.554
0.162
−0.144
−0.129
−0.144
1526
11489411

rotenone
20
−2.235
−4.842
−4.233
−2.300
−0.346
−2.362
−1.812
−1.341
−2.365
1527
11488273

mizoribine
20
−0.681
0.264
−1.321
−0.362
0.646
−0.205
−0.173
−0.106
−0.267
1528
11489375

sulfamonomethoxine
14.28
0.300
0.906
−2.190
−0.680
1.104
0.387
−0.373
−0.427
−0.203
1529
11467971

sulfamonomethoxine
20
−1.144
0.386
−0.526
−0.478
0.665
0.452
−0.320
−0.219
−0.461
1529
11489237

harmaline
18.66
−0.434
−0.629
−0.217
−0.760
1.154
1.579
−0.226
−0.214
−0.203
1530
11467758

harmaline
20
0.790
0.791
−0.838
0.032
0.388
−0.615
−0.533
−0.659
−0.125
1530
11488227

ebselen
14.58
−1.470
0.244
−0.380
−0.959
−0.844
−0.439
−0.938
−0.999
−0.627
1531
11467888

ebselen
20
−0.617
1.192
−0.905
−0.192
−4.078
−1.821
−2.264
−3.031
−0.239
1531
11489257

zomepirac
13.72
−0.137
0.596
−1.027
−0.815
0.497
0.878
−0.181
−0.162
−0.186
1533
11467927

zomepirac
20
−0.791
0.928
−0.589
−0.794
0.402
−0.581
0.342
0.552
−0.179
1533
11488771

piperine
14.02
1.753
−0.553
−0.741
−0.378
−0.318
−0.301
0.020
−0.005
0.060
1534
11467622

piperine
20
0.565
−0.406
−1.093
−0.009
0.688
0.269
−0.944
−1.088
−0.526
1534
11487865

midodrine
15.74
−0.603
0.608
−1.667
−0.627
0.636
0.698
−0.629
−0.303
−1.198
1535
11467339

midodrine
20
−0.509
0.297
−0.795
−0.346
0.666
0.184
−0.628
−0.512
−0.732
1535
11489361

p-fluorophenylalanine
20
0.072
1.220
−1.136
−0.627
0.637
0.280
−0.118
0.011
−0.390
1537
11488718

morin
20
−0.962
1.309
−0.293
−2.534
0.880
−0.180
−0.557
−0.445
−0.685
1538
11488531

monocrotaline
12.3
−0.074
0.717
−2.328
−1.116
0.234
0.515
−0.758
−0.506
−1.109
1539
11467751

monocrotaline
20
−0.637
0.277
−1.519
−0.263
1.636
0.283
−1.124
−1.043
−1.085
1539
11488722

thiamylal
20
0.131
0.166
−0.754
−0.672
0.362
0.190
−0.453
−0.487
−0.252
1570
11488200

pentobarbital
20
0.149
1.143
−0.468
−0.137
−0.496
0.095
0.061
0.008
0.101
1572
11489807

thiopental
20
−0.167
−0.081
−1.043
−0.426
0.356
−0.299
0.646
0.672
0.427
1573
11489814

chlordiazepoxide
20
−1.397
0.117
−1.872
−0.837
0.465
0.132
−0.015
0.215
−0.409
1575
11488973

pomiferin
20
−2.196
−3.179
−3.847
−1.730
−0.899
−2.458
−0.984
−0.931
−0.914
1576
11488615

dimercaptopropanol
20
0.558
0.652
−2.089
0.155
0.556
0.282
−0.488
−0.408
−0.474
1577
11489034

harmalol
19.98
0.225
−0.390
−1.308
−0.761
−0.130
8.863
−0.142
−0.065
−0.282
1578
11467759

harmalol
20
0.188
0.143
−0.505
−0.800
−0.419
6.615
0.839
0.778
0.846
1578
11488372

Ng-methyl-L-arginine acetate
20
−0.533
0.021
−0.692
−0.870
−0.128
0.182
−0.355
−0.422
−0.156
1581
11489298

beta-propiolactone
20
0.044
0.942
−0.834
−0.403
0.386
0.121
−0.590
−0.642
−0.415
1582
11489798

rhapontin
20
−0.359
0.348
−1.009
−0.981
0.073
0.179
0.675
0.675
0.559
1583
11489321

guaiazulene
20
−0.274
0.237
−1.147
−0.886
1.360
−0.055
−0.067
−0.071
0.029
1585
11488905

spermidine
20
0.047
0.821
0.897
−0.323
−0.154
0.029
−0.507
−0.455
−0.539
1586
11488690

lividomycin
20
−1.398
−0.063
−1.482
−0.929
0.368
0.116
−0.417
−0.533
−0.026
1587
11488970

usnic acid
20
−0.677
0.145
−2.122
−0.863
0.866
0.479
−0.671
−0.371
−1.189
1588
11488560

leucine enkephalin
20
0.081
1.105
−0.846
−0.601
−0.107
−0.167
−0.451
−0.320
−0.547
1589
11488993

terfenadine
8.48
−0.199
−0.604
−1.333
−0.174
0.266
−0.611
−0.299
−0.358
−0.157
1590
11467286

N-(9-fluorenylmethoxycarbonyl)-L-leucine
20
0.170
1.110
−0.823
0.228
1.863
−1.594
−0.510
−0.624
−0.172
1591
11489284

N-(g)-nitro-L-arginine
20
−1.111
−0.073
−0.921
−0.297
0.542
−0.969
−0.300
−0.203
−0.429
1594
11489294

gambogic acid
20
−5.274
−8.275
−6.255
−3.614
−3.708
−5.807
ND
ND
ND
1597
11488204

safrole
20
−1.569
0.106
−1.653
−0.743
1.151
0.308
0.319
0.366
0.150
1599
11488591

actinonin
20
−0.831
−0.270
−1.219
−0.829
1.177
0.354
0.189
−0.113
0.830
1600
11488444

pimpinellin
20
−0.369
1.040
−0.698
−0.031
1.874
−0.988
0.229
0.264
0.086
1601
11488536

biochanin A
20
−0.454
−0.069
−1.052
−0.316
0.948
−0.017
0.715
0.513
0.928
1602
11487863

succinylsulfathiazole
11.26
−0.619
−0.325
−1.459
−0.741
0.734
0.482
0.114
0.018
0.279
1603
11467850

succinylsulfathiazole
20
−0.607
0.111
−0.718
−0.673
0.617
0.367
−0.361
−0.409
−0.239
1603
11489762

phthalylsulfathiazole
9.92
−0.354
−0.359
−1.114
−0.293
0.995
0.373
−0.443
−0.394
−0.451
1604
11468017

fluconazole
20
0.018
1.381
0.188
−0.480
0.167
0.741
−0.329
−0.543
0.216
1605
11489423

althiazide
10.42
0.474
1.673
−0.458
−0.163
−0.976
0.491
−0.293
−0.138
−0.554
1606
11467869

althiazide
20
0.218
2.149
−0.724
0.272
1.286
1.305
−0.320
−0.202
−0.491
1606
11489183

lovastatin
9.88
−1.137
−2.217
−2.530
−0.122
−1.374
−1.628
0.334
0.280
0.382
1607
11467664

lisinopril
9.86
0.378
0.387
−0.230
−0.202
0.395
0.265
−1.562
−1.629
−1.109
1608
11467449

lisinopril
20
−0.611
0.030
−1.223
−0.397
0.590
0.412
−0.763
−0.837
−0.472
1608
11489272

gedunin
20
1.017
−0.064
0.444
1.552
−1.448
0.455
−0.592
−0.374
−0.990
1609
11488050

hesperetin
13.24
−0.860
−0.368
−1.684
−0.633
0.674
0.367
−1.018
−1.000
−0.900
1610
11467272

hesperetin
20
−0.764
0.123
−1.157
−0.650
0.147
−0.348
−0.680
−0.463
−0.959
1610
11489609

glimepiride
8.16
0.927
0.600
−1.071
−0.088
0.764
1.009
0.180
0.350
−0.210
1624
11467799

irbesartan
20
1.023
0.581
−1.038
−0.454
1.092
−0.331
−0.652
−0.729
−0.328
1635
11489491

milrinone
18.94
0.265
1.049
−0.224
−0.030
0.704
0.140
−0.026
−0.046
0.005
1666
11468213

ganciclovir
15.68
−0.790
0.414
−1.421
−0.148
0.593
0.005
−0.452
−0.231
−0.809
1670
11467987

oxaprozin
13.64
0.551
0.385
0.442
0.325
−0.224
−0.071
−0.486
−0.537
−0.301
1672
11468208

oxaprozin
20
−0.176
0.847
−0.958
−0.993
1.017
−0.994
0.297
0.381
0.102
1672
11489512

propofol
22.44
0.480
−0.249
0.018
0.039
−0.419
0.242
0.262
0.387
−0.047
1677
11468079

raloxifene
8.44
2.037
−0.803
−0.189
0.287
1.547
0.232
−0.639
−0.610
−0.575
1694
11468010

famciclovir
20
−1.094
−0.720
−0.988
−0.488
0.599
0.779
−0.135
0.125
−0.573
1696
11488917

letrozole
14.02
−1.150
−0.488
−1.505
−0.128
0.554
−0.105
0.806
0.656
0.942
1698
11468173

metformin
30.96
−0.388
1.857
−0.276
0.175
0.413
0.597
0.297
0.516
−0.263
1714
11467152

fluvastatin
9.72
−1.351
−3.178
−3.244
0.811
−1.812
−2.180
−0.209
−0.217
−0.148
1736
11468007

gabapentin
23.36
0.021
0.087
−0.449
−1.028
0.336
−0.111
−0.193
0.105
−0.747
1764
11468009

nilutamide
12.6
−0.653
−0.364
0.031
−0.324
0.641
−0.135
−0.933
−0.970
−0.685
1765
11468076

nilutamide
20
−0.193
0.303
−1.291
−0.670
0.649
−0.409
−1.586
−1.507
−1.482
1765
11489789

mesalamine
26.12
−0.213
0.208
−0.560
−0.257
−0.577
−0.325
−0.451
−0.499
−0.270
1778
11468217

moxonidine
16.56
−1.463
−0.492
−0.691
−0.724
2.064
0.163
−0.167
−0.013
−0.459
1779
11468164

omeprazole
11.58
0.321
0.461
−1.418
−0.768
0.355
0.828
−0.681
−0.500
−0.914
1782
11467641

modafinil
20
−1.484
−0.436
−0.859
−0.387
0.644
0.141
−0.907
−0.764
−0.985
1788
11489528

risperidone
9.74
−1.004
−0.813
−0.267
0.478
1.159
0.243
0.887
0.615
1.266
1795
11468177

ticlopidine
15.16
−0.687
0.326
−1.403
−0.863
1.252
−0.316
0.200
0.254
0.017
1821
11467195

dorzolamide
12.32
−0.030
−0.808
−0.323
0.180
−0.044
−0.076
0.990
0.975
0.829
1829
11468264

sildenafil
20
−0.402
−0.645
−0.519
0.312
1.028
−0.864
−0.496
−0.551
−0.254
1835
11489464

rofecoxib
20
−0.930
0.935
−2.253
−1.000
1.755
0.131
0.209
0.138
0.363
1837
11488262

epigallocatechin-3-monogallate
20
1.161
1.521
−0.164
−0.586
0.177
0.290
−0.083
−0.109
−0.079
1859
11487984

MY-5445
20
−0.255
0.348
−0.285
−0.571
1.358
−1.229
0.164
0.193
0.113
1865
11489636

bovinocidin
20
0.168
0.970
0.453
−0.385
0.357
−0.045
−0.611
−0.436
−0.867
1898
11488692

flucytosine
30.98
−0.729
0.283
−0.714
−0.503
0.520
0.107
−0.687
−0.685
−0.567
1910
11468082

7-nitroindazole
20
−0.990
0.589
−1.157
−0.933
0.565
0.618
−0.238
−0.178
−0.276
1912
11489531

aminocyclopropanecarboxylic acid
20
−0.938
0.420
−1.980
−0.372
−0.055
0.213
−0.566
−0.573
−0.433
1923
11489291

baicalein
20
−0.456
1.556
−1.632
−2.552
0.851
1.049
0.699
0.444
1.140
1950
11488282

betulinic acid
8.76
0.910
1.086
−2.668
−1.366
−0.038
0.751
−0.037
0.128
−0.370
1960
11467565

caffeic acid
22.2
−0.291
0.443
−0.963
−1.448
−1.104
0.512
−0.136
−0.192
−0.004
1978
11468050

caffeic acid
20
−1.020
−0.153
−1.817
−4.427
−2.045
−0.003
−0.914
−0.783
−0.966
1978
11489428

clioquinol
13.1
−1.660
−1.663
−1.672
2.483
−1.879
1.216
−0.761
−0.811
−0.536
1999
11468034

pentetic acid
10.16
0.590
−0.276
0.586
0.181
−0.104
0.444
0.509
0.395
0.633
2030
11468089

disulfiram
13.48
−3.107
0.167
−1.891
−2.228
−0.898
−5.825
−1.156
−1.020
−1.252
2038
11467245

disulfiram
20
−5.476
−6.037
−5.086
−3.244
−3.188
−1.545
−2.620
−4.097
0.927
2038
11488992

thiorphan
15.8
0.169
0.495
−1.618
−0.273
−0.185
0.083
−0.070
−0.004
−0.186
2041
11467781

ellipticine
16.24
−4.355
−6.206
−3.881
−1.483
1.606
−5.622
−1.053
−0.425
−2.134
2057
11467762

formononetin
20
0.658
0.203
0.503
0.495
0.115
−0.178
0.656
0.471
0.947
2070
11488376

fusaric acid
22.32
−0.549
−0.122
−1.387
−0.832
0.347
−0.004
−0.077
−0.052
−0.117
2078
11467590

gabexate
12.44
−0.955
−0.212
−0.701
−0.488
1.154
−0.161
0.540
0.319
0.884
2080
11468156

miltefosine
20
−0.727
0.150
−1.088
−0.429
0.493
−0.928
0.221
0.221
0.164
2097
11488495

hydroquinone
20
−5.481
−8.318
−6.520
−4.469
−4.148
−4.999
−3.360
−3.940
−1.450
2101
11489488

indole-3-carbinol
20
−0.133
0.851
−0.881
−1.071
1.260
0.096
0.188
0.243
0.074
2109
11489526

kaempferol
13.98
−0.013
0.060
−0.352
−2.485
−1.322
−0.523
−0.278
−0.322
−0.141
2121
11468246

luteolin
13.98
−0.627
−0.637
−0.209
−1.473
0.247
−0.440
−0.240
−0.379
0.091
2137
11468018

myricetin
12.56
−0.099
−0.306
−1.209
−1.577
0.077
0.084
−0.006
−0.018
0.019
2181
11467613

clorgyline
14.7
−0.489
0.494
−0.460
−0.631
1.023
0.228
0.051
0.338
−0.541
2203
11467492

picotamide
10.62
−1.774
−0.210
−0.155
−0.285
0.828
−0.504
−1.237
−1.260
−0.986
2241
11467267

piribedil
13.4
−0.355
0.175
0.905
0.249
0.639
0.264
0.451
0.552
0.153
2245
11468128

resveratrol
17.52
0.069
1.364
−0.765
−0.462
1.992
−0.119
0.063
0.159
−0.147
2269
11467656

resveratrol
20
−0.963
0.437
−1.562
−3.524
−0.339
−1.039
−1.233
−1.262
−0.925
2269
11489313

selegiline
21.36
−0.251
0.099
−0.278
−0.594
−0.032
0.224
0.124
0.155
0.035
2284
11467700

S-nitroso-N-acetylpenicillamine
20
−0.254
0.568
−0.843
−0.321
0.213
0.155
−0.292
−0.237
−0.342
2294
11489282

tetrahydropalmatine
20
0.104
0.597
−0.758
−0.961
1.124
0.035
0.687
0.644
0.625
2321
11488552

D,L-threo-3-hydroxyaspartic acid
20
−0.438
−0.580
−0.811
−0.716
0.366
0.934
−0.297
−0.299
−0.195
2325
11489730

tranilast
20
0.160
−0.384
−0.710
−0.037
0.080
0.755
−0.955
−0.825
−1.088
2335
11487858

vinpocetine
11.42
1.168
1.960
0.886
0.174
1.353
0.297
0.092
0.142
−0.024
2359
11467416

vinpocetine
20
0.669
0.260
−1.030
0.242
1.318
−1.089
−0.370
−0.400
−0.250
2359
11489345

zardaverine
14.92
0.491
1.567
−0.675
−0.382
1.406
0.166
0.022
0.060
−0.077
2372
11468125

meloxicam
20
−0.324
0.573
−0.329
−0.929
0.224
0.207
−1.255
−0.850
−1.857
2407
11488757

procainamide
17
0.503
1.195
−0.573
−1.152
0.773
0.492
−0.328
−0.116
−0.696
2431
11467485

procainamide
20
−1.102
1.117
−1.144
−0.366
0.351
1.015
−0.044
0.057
−0.247
2431
11489111

chrysanthemic acid
20
−0.009
0.472
−0.908
0.060
0.472
0.611
−0.693
−0.657
−0.598
2475
11489498

diazinon
20
−0.010
0.074
−1.251
−0.558
0.998
0.298
−1.047
−0.762
−1.349
2476
11489042

ethion
20
1.318
0.899
−1.264
−0.987
0.841
0.432
0.404
0.487
0.229
2477
11489041

methyl parathione
20
1.967
0.145
−0.341
−0.353
0.218
0.414
0.500
0.500
0.450
2478
11489665

coumophos
20
3.041
−0.106
−0.752
0.860
−0.085
0.083
0.029
−0.186
0.479
2479
11489661

azinphos methyl
20
1.987
0.997
−0.974
0.280
0.702
0.900
0.452
0.405
0.482
2480
11489662

disulfoton
20
0.122
0.226
−1.501
−0.989
0.929
0.572
0.002
0.022
−0.005
2481
11489672

mevinphos
20
0.130
0.496
−1.230
−0.859
1.071
0.643
−0.949
−1.016
−0.592
2482
11489673

naled
20
−0.669
−0.307
−1.559
−0.313
0.120
0.966
0.273
0.432
−0.065
2483
11489674

dichlorvos
20
−0.805
0.791
−2.000
−0.589
0.668
0.165
0.118
0.375
−0.339
2484
11489043

oxdemetonmethyl
20
−0.511
0.724
−0.494
−0.255
0.833
0.196
0.122
0.246
−0.125
2485
11489675

dimethoate
20
0.942
0.487
−1.273
0.139
1.036
0.837
−1.431
−1.309
−1.363
2486
11489677

malathion
20
0.419
1.406
−1.414
0.397
1.064
−0.938
−0.209
−0.397
0.287
2487
11489044

phosalone
20
2.358
0.897
−0.750
−0.407
−1.945
0.522
−0.767
−0.578
−0.959
2488
11489678

methamidophos
20
2.972
1.038
−0.710
−0.473
0.289
0.635
−1.162
−0.894
−1.435
2489
11489679

phorate
20
0.649
0.220
−0.526
−0.116
0.740
−0.612
0.282
0.133
0.562
2490
11489676

dacthal
20
−0.954
−0.561
−2.116
−0.046
0.253
−0.159
−0.916
−1.062
−0.402
2491
11489692

propazine
20
−0.634
−0.606
−1.928
−0.648
0.725
−0.083
−0.837
−0.761
−0.783
2492
11489693

propanil
20
−0.873
−0.530
−1.657
−0.091
−0.085
−0.108
0.576
0.574
0.511
2493
11489694

simazine
20
−0.698
−0.125
−0.829
−0.390
0.382
−0.360
−0.386
−0.400
−0.238
2494
11489695

atrazine
20
−0.129
0.081
−0.347
−0.236
0.634
−0.617
−0.342
−0.242
−0.436
2495
11489696

diuron
20
−0.314
0.513
−1.203
−0.105
1.122
0.530
0.400
0.580
0.070
2496
11489045

tebuthiuron
20
−0.844
0.546
−0.407
−0.317
1.164
0.051
−1.404
−1.187
−1.523
2497
11489697

dicamba
20
−0.500
−0.078
−1.617
−0.328
0.818
0.278
−1.740
−1.356
−2.129
2498
11489698

benfluralin
20
−1.241
0.210
−1.927
−0.527
0.989
−0.193
−0.791
−0.809
−0.558
2499
11489699

prometon
20
−0.783
−0.867
−2.162
−0.905
1.142
−0.259
−0.744
−0.632
−0.790
2500
11489700

metolachlor
20
−1.168
−0.705
−2.217
−0.659
0.959
0.156
−0.487
−0.279
−0.763
2501
11489701

dichlobenil
20
−0.587
−0.660
−1.515
−0.543
−0.032
−0.025
−0.784
−0.670
−0.819
2502
11489702

prometryn
20
−0.336
−0.095
−1.458
−0.891
1.172
0.093
−0.288
−0.130
−0.514
2503
11489703

trifluralin
20
−0.731
−0.083
−1.149
−0.333
0.868
−0.378
−0.480
−0.577
−0.147
2504
11489704

bentazon
20
−0.857
−0.173
−0.852
−0.531
0.539
−0.324
−1.017
−0.977
−0.850
2505
11489705

2,4-dichlorophenoxyacetic acid
20
−0.123
0.028
−1.450
−0.625
0.554
0.309
−0.423
−0.237
−0.669
2506
11489671

2,4-dichlorophenoxybutyric acid
20
0.337
−0.337
−1.368
−0.479
0.758
0.711
−0.476
−0.439
−0.423
2507
11489670

2,4,5-trichlorophenoxyacetic acid
20
−0.192
0.831
−1.619
−0.215
1.217
0.531
−0.669
−0.420
−0.977
2508
11489040

alachlor
20
−3.839
−7.372
−3.820
−1.048
−0.917
−5.053
−2.717
−2.562
−2.460
2509
11489669

2,4-dichlorophenoxyacetic acid, methyl ester
20
0.777
0.234
−0.975
−0.464
0.503
0.708
−1.200
−0.982
−1.362
2510
11489667

2,4-dichlorophenoxybutyric acid, methyl ester
20
0.178
−0.331
−0.845
−0.247
0.476
0.749
−0.401
−0.336
−0.426
2511
11489668

2,4,5-trichlorophenoxyacetic acid, methyl ester
20
0.801
0.136
−0.691
0.201
−0.070
−0.066
1.089
1.061
0.964
2512
11489666

glyphosate
20
0.663
1.910
−0.806
−0.537
0.189
1.051
0.944
1.048
0.584
2513
11489663

2,4-dichlorophenoxyacetic acid, isooctyl ester
20
0.656
0.224
−0.700
−0.029
−0.120
0.575
−0.116
0.002
−0.296
2514
11489664

2,4,5-trichlorophenoxyacetic acid, isooctyl ester
20
1.258
0.541
−0.607
0.066
0.118
0.997
−0.759
−0.689
−0.713
2515
11489657

chlorpropham
20
0.050
0.553
−1.623
−0.832
0.158
0.110
0.316
0.598
−0.384
2516
11487860

propachlor
20
−5.583
−8.358
−6.698
−4.270
−3.747
−4.882
−3.430
−4.130
−1.250
2517
11489658

S,S,S,-tributylphosphorotrithioate
20
4.229
1.660
−0.580
0.275
−0.757
0.365
−1.911
−1.877
−1.570
2518
11489659

triallate
20
0.579
0.532
−1.481
−0.214
0.153
0.374
−0.246
−0.231
−0.192
2519
11489660

paradichlorobenzene
20
−0.777
0.640
−1.083
−0.184
1.100
0.599
0.050
0.050
0.030
2520
11489685

pentachlorophenol
20
−2.253
−5.275
2.658
−3.529
0.192
−3.176
−0.930
−0.905
−0.763
2521
11489686

carbofuran
20
2.257
0.452
−1.613
−0.481
0.504
0.315
−0.925
−0.770
−1.020
2522
11489687

chlorpyrifos
20
0.980
0.799
−1.253
0.032
0.455
−0.067
−0.534
−0.446
−0.545
2523
11489046

acephate
20
−0.491
−0.395
−1.983
−0.831
0.882
0.136
0.002
−0.018
0.085
2524
11489541

temefos
20
−0.761
−0.378
−1.645
−0.119
0.681
0.316
−1.403
−1.230
−1.431
2527
11489689

bendiocarb
20
0.816
−0.186
−1.742
−0.553
1.492
−0.178
−0.141
0.016
−0.390
2528
11489542

fenthion
20
0.594
0.527
−1.111
0.015
1.063
0.845
−0.270
−0.234
−0.224
2529
11489047

ethoprop
20
0.070
−0.054
−2.177
−0.500
0.988
0.271
−0.222
0.003
−0.595
2530
11489690

propoxur
20
2.120
0.743
−1.580
−0.736
0.679
−0.200
−0.473
−0.266
−0.729
2531
11489048

propargite
20
−0.582
0.065
−2.401
−0.388
0.208
0.130
−0.985
−1.134
−0.455
2532
11489691

dichlorodiphenyltrichloroethane
20
−1.165
0.206
−1.627
−0.807
0.757
0.399
−0.430
−0.013
−1.105
2533
11489049

dichlorodiphenyldichloroethylene
20
−0.282
−0.072
−1.949
−0.753
3.563
0.831
−0.433
−0.302
−0.572
2534
11489681

toxaphene
20
−1.096
−1.562
−2.310
0.375
−0.885
−0.903
−0.017
0.239
−0.491
2535
11489683

chlordane
20
−0.052
0.691
−0.712
0.713
1.698
−0.640
−0.632
−0.565
−0.598
2536
11489684

methoxychlor
20
−0.656
−0.734
−0.510
−0.180
0.503
−0.578
−1.000
−0.934
−0.885
2537
11489706

heptachlor
20
−0.375
0.049
0.387
0.337
0.601
0.657
−0.593
−0.449
−0.729
2538
11489707

strobane
20
−0.034
−0.266
−1.114
−0.727
0.352
−0.198
−0.368
−0.234
−0.535
2539
11489708

aldrin
20
−0.489
0.264
−1.145
−0.757
0.701
0.343
−1.254
−1.009
−1.458
2540
11489710

endosulfan
20
−1.047
0.622
−1.178
0.278
0.558
0.482
−0.283
−0.161
−0.434
2541
11489709

benzylbutylphthalate
20
−1.041
−0.007
−1.437
−0.679
−0.168
−0.174
−0.454
−0.411
−0.407
2542
11489621

4-nonylphenol
20
0.969
1.011
0.389
0.271
−0.420
0.444
0.176
0.683
−0.843
2543
11489648

acetochlor
20
−0.632
0.978
0.226
0.015
−0.124
0.075
−0.260
−0.318
−0.045
2544
11489731

dimethyl 4,4-o-phenylene-bis
20
−0.641
−1.181
−1.142
0.613
0.454
0.393
−0.632
−0.380
−1.036
2546
11488462

sanguinarine
12.04
−5.346
−8.386
−5.277
−3.957
−1.134
−2.136
−1.550
−2.600
0.830
2549
11468135

sanguinarine
20
−1.023
−1.435
−2.258
−0.858
−0.697
−5.748
−2.099
0.009
−6.006
2549
11488540

chloramphenicol
20
−0.216
1.169
−0.228
−0.337
−0.659
0.489
0.333
0.087
0.718
2550
11487899

primaquine
15.42
−5.256
−8.264
−6.088
−3.330
−3.563
1.155
0.595
0.622
0.415
2551
11467624

primaquine
20
0.984
2.199
−1.333
0.152
0.792
−5.704
0.743
0.674
0.708
2551
11488703

1,2-dimethylhydrazine
20
−1.633
0.180
−1.531
−0.907
1.083
0.303
0.739
0.717
0.626
2553
11488593

conessine
20
−0.739
0.461
−1.459
−0.262
0.970
1.197
−1.055
−1.058
−0.871
2554
11488731

diaziquone
20
−0.617
0.938
−1.450
−0.438
0.106
−0.829
0.398
0.365
0.469
2555
11489002

methylmethane
20
−1.159
0.234
−1.330
−0.924
0.909
0.221
−0.516
−0.362
−0.754
2557
11488733

benzo[a]pyrene
20
0.501
0.381
−0.946
−0.254
1.095
0.652
0.246
0.366
0.020
2558
11488897

cadmium acetate
20
−1.393
0.954
−1.896
−1.276
−1.066
−2.166
1.464
1.340
1.491
2559
11488294

3-methylcholanthrene
20
−1.203
0.397
−1.878
−0.411
0.849
0.846
−0.168
0.112
−0.629
2560
11488910

2,4-dinitrophenol
20
−1.024
−1.036
−0.839
0.489
1.402
0.031
−0.088
−0.131
−0.003
2561
11488489

penicillic acid
20
−1.082
0.598
−0.634
−0.210
−1.003
−0.243
−1.311
−1.206
−1.244
2565
11488407

desmethyldihydrocapsaicin
20
0.046
0.130
−1.248
−0.672
0.636
0.605
−0.576
−0.497
−0.563
2566
11488907

dichlorphenamide
13.1
0.692
0.479
−1.076
−0.465
0.222
0.842
−0.442
−0.401
−0.441
2570
11467957

tubocurarine
20
−0.589
0.899
−0.749
−0.866
0.451
0.387
−0.325
−0.272
−0.370
2572
11489151

tinidazole
16.18
−1.120
0.167
−1.767
−0.967
0.480
0.150
−0.611
−0.104
−1.508
2575
11467914

tinidazole
20
−1.121
1.810
−0.734
0.347
0.558
−0.492
0.054
0.148
−0.174
2575
11488464

benzyl isothiocyanate
20
−0.764
−0.015
−1.178
−0.141
−0.803
−0.443
−0.932
−0.755
−1.123
2576
11488668

thiodiglycol
20
−0.423
3.392
−1.250
0.184
0.861
1.028
−0.492
−0.456
−0.426
2579
11488223

ticarcillin
10.4
0.216
1.089
−0.127
0.047
0.415
0.002
0.183
0.315
−0.126
2586
11468215

crotamiton
19.68
1.013
1.174
1.423
−1.055
0.190
0.084
0.653
0.997
−0.184
2660
11468099

crotamiton
20
−0.270
0.010
−0.870
−1.322
0.638
0.073
−0.044
0.319
−0.742
2660
11489516

iodipamide
3.5
−0.961
−0.669
−0.253
0.039
0.913
−0.891
0.060
−0.070
0.290
2685
11468087

epirizole
17.08
−0.756
0.455
−1.614
−0.525
0.765
−0.453
−1.362
−1.296
−1.279
2702
11467180

pyridoxine
23.64
−0.182
−0.160
−1.535
−0.421
0.937
0.286
0.246
0.149
0.398
2709
11467771

ethynylestradiol 3-methyl ether
12.88
−0.071
−0.281
−0.915
−0.824
0.867
0.724
−0.938
−0.690
−1.272
2710
11467994

testosterone propionate
11.62
0.371
1.906
−0.649
−0.434
−0.576
0.346
−0.784
−0.579
−1.063
2717
11467549

hymecromone
22.7
0.273
0.379
0.139
−0.454
0.284
1.733
1.085
0.979
1.081
2732
11468049

ozagrel
17.52
0.168
0.739
−0.543
−0.086
1.631
0.251
0.882
0.807
0.867
2742
11468127

metyrapone
17.68
−1.204
−0.176
−0.539
−0.268
−0.087
0.372
0.354
0.375
0.234
2743
11468052

zalcitabine
18.94
−0.670
0.005
−0.535
−0.518
0.899
0.157
0.059
0.048
0.066
2747
11468185

methotrimeprazine
12.18
−0.002
−0.906
−1.154
−0.140
0.033
−0.199
0.223
0.177
0.274
2752
11467945

etidronic acid
19.42
−0.135
−0.143
−1.408
−0.600
1.192
0.462
0.026
0.022
0.025
2764
11468011

felbinac
18.84
−0.265
1.401
−0.648
0.052
2.434
0.714
−0.928
−0.838
−0.949
2776
11468041

clebopride
10.7
−0.607
−0.674
−0.911
0.709
1.496
0.179
0.070
−0.044
0.284
2777
11467528

clebopride
20
−0.658
0.232
−1.789
−0.237
1.468
0.602
0.323
0.406
0.078
2777
11488583

canrenoic acid
11.16
0.484
−0.790
−0.668
−0.667
1.092
−0.361
0.474
0.407
0.485
2784
11467296

indomethacin
11.18
−0.249
−0.314
−1.259
−0.535
2.161
−2.360
−0.207
−0.199
−0.172
2797
11467420

indomethacin
20
1.222
0.596
−1.394
1.943
0.846
0.107
1.771
1.318
2.396
2797
11488786

carmofur
20
−0.126
0.283
−2.715
−0.528
−0.305
−0.087
−0.338
−0.352
−0.283
2801
11487842

bemegride
25.78
−0.962
2.019
0.024
0.808
0.108
0.970
−0.279
−0.069
−0.658
2819
11468030

domperidone
9.4
0.888
0.194
−0.331
0.126
0.152
0.276
−0.099
−0.029
−0.234
2830
11467609

S(+)-terguride
11.74
−0.531
−0.681
−0.964
−0.585
0.083
−0.138
0.926
0.474
1.666
2844
11468093

moxisylyte
14.32
0.426
−0.135
−1.330
−0.807
0.441
−0.330
−0.147
−0.127
−0.207
2847
11467190

cilostazol
20
−0.200
0.623
−0.215
−0.908
2.587
0.481
0.157
−0.113
0.736
2857
11488934

benzbromarone
9.44
−0.067
0.079
0.360
−1.098
0.591
0.340
0.195
0.088
0.380
2873
11467518

glutamine
20
−0.030
0.880
−0.888
−0.851
2.225
0.452
0.213
0.208
0.182
2880
11489193

cyclacillin
11.72
−0.221
−0.257
1.769
−0.107
−0.360
−0.886
0.039
−0.069
0.250
2884
11468268

meticrane
14.52
0.323
1.068
−1.627
−0.012
0.443
0.527
0.003
0.066
−0.179
2898
11467159

trimethadione
27.94
−1.300
0.162
−1.825
−0.503
1.082
0.085
−0.930
−0.741
−1.139
2900
11467663

dosulepin
13.54
1.339
0.875
−0.806
0.069
0.095
0.997
−0.215
0.065
−0.761
2911
11467636

trapidil
19.48
−0.011
0.155
−0.788
−0.215
0.898
0.082
−0.158
−0.039
−0.378
2920
11468160

bromperidol
9.52
1.393
0.434
−0.005
0.033
1.607
0.998
0.081
0.060
0.099
2922
11467657

iodipamide
20
0.451
−0.423
−1.303
−0.147
1.515
−0.253
0.729
0.633
0.860
2935
11488886

ioxaglic acid
3.16
−0.293
1.071
−0.820
−0.321
0.042
0.422
−0.333
−0.355
−0.237
2957
11468210

dilazep
6.62
−1.111
−0.641
−1.284
−0.865
0.972
−0.150
0.109
−0.054
0.371
2997
11467384

diphenidol
12.92
−0.622
1.158
−0.364
−0.471
0.308
1.413
1.217
1.221
0.975
3036
11467400

diflorasone diacetate
8.08
−0.860
−0.652
−1.681
−0.039
−0.021
−0.871
−0.080
−0.240
0.240
3043
11467767

alpha-santonin
16.24
0.154
0.732
0.149
0.619
−0.403
−1.010
0.249
0.056
0.582
3047
11468218

santonin
20
−1.099
0.556
−1.064
−0.433
0.461
−0.759
−0.385
−0.478
−0.147
3047
11488515

guanethidine
20.18
0.543
1.295
−0.740
−0.504
0.048
0.290
0.135
0.031
0.319
3055
11467465

guanethidine
20
−0.898
0.054
−1.416
−0.594
0.976
−0.026
0.145
0.224
0.027
3055
11488919

panthenol (D)
19.48
−0.109
0.699
−1.407
−0.466
0.430
0.048
−1.611
−1.685
−1.206
3060
11467170

cefoperazone
6.2
−0.399
2.066
−0.776
−0.184
0.148
0.967
0.346
0.437
0.075
3063
11467475

methimazole
35.04
0.022
−0.033
−1.626
−0.369
0.106
−0.372
−0.090
−0.159
0.065
3092
11467934

hydrocotarnine
18.08
−0.296
−0.016
−2.202
−0.818
0.946
−0.062
0.177
0.287
−0.092
3100
11467753

hydrocotarnine
20
−1.349
−0.397
−1.162
−0.841
0.878
0.124
0.560
0.356
0.861
3100
11489209

flavoxate
10.22
−1.126
2.109
−0.174
−0.324
0.521
1.276
−0.112
0.059
−0.431
3101
11467390

benoxinate
12.96
−0.753
−0.177
−0.975
−0.410
1.135
−0.489
0.348
0.588
−0.254
3127
11467205

dydrogesterone
12.8
0.425
−0.222
−0.997
−0.554
0.729
0.873
−0.141
−0.090
−0.220
3129
11467819

rescinnamin
6.3
1.773
2.812
−0.246
−0.048
1.685
0.566
0.378
0.262
0.541
3141
11467716

piretanide
11.04
0.737
2.322
−0.288
−0.577
−0.655
0.188
−0.246
−0.212
−0.290
3168
11468195

lisuride
11.82
−0.329
1.157
−2.069
−0.838
0.023
0.617
−0.899
−0.922
−0.723
3169
11467254

cinnarazine
10.86
−0.692
1.178
−0.009
−0.711
1.252
−0.519
0.362
0.338
0.349
3172
11467426

prothionamide
20
0.236
1.276
−1.091
−0.056
1.300
0.156
−0.310
−0.318
−0.282
3182
11487835

acetohexamide
12.34
−1.368
−0.025
−1.503
−1.107
1.642
−0.453
−0.862
−0.945
−0.568
3186
11467203

procarbazine
18.08
1.082
0.133
0.595
0.240
−0.880
−0.008
1.248
1.288
0.922
3199
11468260

urapidil
10.32
−0.651
−0.283
−0.597
−0.538
0.411
0.487
−0.066
−0.021
−0.161
3202
11468053

urapidil
20
−0.316
−0.374
−0.668
−0.361
0.438
0.151
−0.168
0.035
−0.486
3202
11488988

salsalate
20
−0.591
0.602
−1.448
−0.733
0.320
0.435
−1.090
−0.859
−1.360
3235
11488509

batyl alcohol
20
−0.197
1.347
0.138
0.201
−0.324
0.278
−0.371
−0.686
0.366
3250
11489425

alverine citrate
14.22
1.004
0.883
0.006
−0.087
1.231
1.451
−0.641
−0.545
−0.756
3256
11467322

mephentermine
24.5
0.521
0.503
−0.784
−0.591
−0.319
0.554
−0.097
0.018
−0.319
3263
11467874

mephentermine
20
−0.969
0.911
−0.450
−1.120
0.882
1.371
−0.210
−0.021
−0.513
3263
11488290

cefamandole
20
−0.861
0.335
−0.518
−0.177
−0.328
0.439
0.018
0.237
−0.428
3264
11489279

phenelzine
29.38
0.907
0.744
−0.341
0.015
0.544
−0.707
0.527
0.552
0.325
3273
11467318

phenelzine
20
0.149
0.907
−0.744
−0.485
0.608
0.437
−0.938
−0.955
−0.629
3273
11488825

ketanserin
20
−1.051
−0.727
−0.987
−0.439
1.244
0.509
−1.015
−0.935
−0.952
3304
11489529

cyproheptadine
13.92
−0.558
0.745
−1.321
0.430
0.366
0.064
−1.166
−0.919
−1.483
3326
11467251

guanfacine
16.26
−0.015
1.119
−1.173
−0.622
1.249
0.613
0.496
0.638
0.110
3368
11467487

thiamine
15.08
−0.247
0.706
0.145
−0.160
1.222
0.284
0.259
0.161
0.412
3382
11467779

isocarboxazid
17.3
−0.205
−0.386
−0.860
−0.637
0.106
−0.005
−0.325
−0.340
−0.230
3383
11467943

(−)-levobunolol
13.72
−0.923
0.019
−1.716
−0.772
1.403
0.049
−0.595
−0.647
−0.372
3452
11467995

umbelliferone
20
0.137
0.726
−1.479
−1.303
0.545
−0.272
−0.788
−0.661
−0.935
3526
11489778

guvacine
20
−1.458
−0.056
−1.711
−0.677
−0.161
0.280
−0.412
−0.678
0.201
3684
11489290

dimaprit
24.8
0.169
0.490
−0.416
2.136
0.016
−0.184
−0.311
−0.403
−0.076
3723
11468131

decamethonium bromide
15.48
0.213
1.342
1.618
0.049
1.665
0.967
0.938
0.940
0.744
3855
11468116

mecamylamine
23.92
1.457
−0.130
0.560
−0.349
−0.583
−0.062
0.123
0.389
−0.447
3856
11468259

ciprofibrate
13.84
−0.930
0.365
−0.632
−0.154
0.271
−0.078
0.572
0.421
0.763
3903
11468224

carprofen
20
−0.827
0.752
−1.838
−0.481
0.724
0.138
−0.857
−0.801
−0.729
4164
11489052

isoetharine
16.72
−0.131
0.237
−0.882
−0.965
−0.727
−0.262
−0.412
−0.399
−0.363
4338
11467897

loxapine
12.2
1.467
0.168
−1.459
−0.312
−0.254
0.366
−0.849
−0.766
−0.897
4362
11467280

loxapine
20
1.067
−0.106
−0.898
−0.731
1.305
−0.072
−0.311
−0.387
−0.065
4362
11489553

megestrol acetate
10.4
0.304
0.577
0.085
0.141
0.953
−0.308
1.288
1.214
1.175
4369
11468104

meglumine
20.5
−1.025
1.957
−0.525
0.293
0.274
0.969
−0.117
−0.089
−0.143
4370
11468032

mesoridazine
10.34
−0.524
−0.524
−0.938
−0.393
0.760
−0.121
−0.812
−0.847
−0.583
4379
11467677

methantheline
11.74
−0.041
1.257
−0.454
0.057
0.199
0.326
−0.068
−0.003
−0.199
4382
11468214

oxamniquine
14.32
−1.195
−1.036
−0.401
−0.392
0.581
−0.104
0.181
−0.060
0.630
4425
11468174

proguanil
15.76
−0.921
−1.029
−0.493
0.189
−0.929
−0.064
−0.480
−0.557
−0.238
4480
11468147

chlorguanide
20
0.105
0.500
−0.742
−0.718
0.276
−0.543
−0.250
−0.129
−0.379
4480
11488951

proparacaine
13.58
0.375
−0.446
0.278
0.031
0.730
−1.020
1.027
0.933
1.013
4481
11468107

protriptyline
15.18
−0.906
−0.995
0.049
0.508
−0.007
−1.335
0.719
0.778
0.438
4487
11468078

trigonelline
20
−1.304
0.777
−1.906
−0.748
0.695
−0.072
−0.372
−0.511
0.035
4895
11488412

fluspirilen
8.42
0.640
−0.546
−0.239
0.538
−0.191
−0.063
−0.910
−0.789
−1.002
23081
11468054

mexamine
20
−0.163
0.061
−0.245
−0.712
1.030
0.234
0.070
0.177
−0.090
52159
11488927

5,7-dichlorokynurenic acid
20
0.384
0.128
−0.711
−0.406
1.628
−0.534
1.079
0.900
1.186
89599
11489815

harmine
18.84
−0.515
−0.633
−2.665
−0.421
−0.521
0.187
0.068
−0.081
0.368
297849
11467761

harmine
20
0.658
−0.104
−2.629
0.463
−0.395
0.396
0.208
−0.039
0.717
297849
11488384

5-fluoroindole-2-carboxylic acid
20
−0.059
−0.383
−0.968
−0.373
0.371
−0.043
−0.105
−0.284
0.279
348755
11489285

1-(2-methoxyphenyl)piperazine
20
−0.289
0.326
−1.047
−0.272
−0.114
−0.744
−0.878
−0.743
−0.933
352677
11489634

clemizole
12.28
0.147
−0.736
0.264
−0.615
1.477
0.226
0.561
0.593
0.349
386963
11467375

amodiaquin
11.24
0.263
−1.051
−1.100
−0.547
0.192
−0.247
0.506
0.360
0.720
467359
11467457

ferulic acid
20
−1.181
0.133
−1.254
−0.844
−0.272
0.169
−0.380
−0.432
−0.191
802058
11489210

glycocholic acid
8.6
−0.392
0.088
−0.789
−0.577
0.470
0.143
−0.950
−0.778
−1.118
821975
11467669

isoliquiritigenin
20
0.088
0.601
−0.121
0.011
0.228
0.089
−0.987
−0.856
−1.073
831758
11488691

succinylacetone
20
−0.870
−0.284
−1.695
−0.770
0.905
0.901
−0.771
−0.884
−0.337
832189
11488283

aspartame
20
−0.475
0.544
−1.203
−0.659
0.815
0.554
0.146
0.172
0.103
832325
11489522

agmatine
20
−0.180
2.210
−0.522
0.134
1.006
0.402
−0.547
−0.388
−0.729
839435
11489424

5-aminopentanoic acid
20
−0.492
−0.549
−1.044
−0.917
0.645
0.309
0.282
0.136
0.534
840551
11489226

anabasine
24.66
−0.010
−0.872
−0.191
−1.113
2.431
0.716
0.141
0.200
−0.013
852250
11467817

anabasine
20
−0.552
−0.450
−0.128
−0.672
0.352
0.635
−1.317
−1.009
−1.645
852250
11489608

nialamide
13.4
−0.341
0.092
0.025
0.394
0.058
−0.726
1.166
1.235
0.796
865102
11468247

7-chlorokynurenic acid
20
0.449
0.838
−0.636
0.461
1.279
−0.539
0.185
0.139
0.247
873168
11489286

7-chloroethyltheophylline
20
−0.272
−0.243
−0.681
−0.631
−0.025
−0.182
−1.393
−1.263
−1.337
907089
11489633

alaproclate
20
−0.052
−0.288
−0.621
−0.073
0.591
0.372
−0.717
−0.426
−1.124
907120
11489469

N,N-dimethylamiloride
20
−0.932
0.150
−1.283
−0.618
0.309
0.249
−0.096
0.113
−0.468
907149
11489431

N,N-hexamethyleneamiloride
20
0.387
−1.805
−1.069
−0.285
0.428
−0.256
−0.015
−0.128
0.273
907181
11489485

2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane
20
−0.819
−0.657
−1.987
−0.474
1.695
−0.140
0.010
−0.031
0.100
907188
11489391

bretylium
16.46
−0.520
−0.045
−0.192
−0.347
0.191
0.295
0.113
0.245
−0.195
907192
11468090

buflomedil
13.02
−0.432
1.151
−0.385
−0.688
0.537
0.464
−0.015
0.037
−0.117
907205
11467574

clofilium
11.8
−2.024
−5.798
−4.093
0.584
−2.010
−3.111
−0.510
−0.876
0.338
907228
11467467

GBR 12909
8.88
−1.147
−0.535
−0.212
0.556
1.362
0.644
0.566
−0.002
1.620
907273
11467534

debrisoquin sulfate
22.82
−0.349
−0.410
−1.458
−0.615
0.684
−0.125
−0.782
−0.655
−0.882
907283
11467520

dihydroergocristine
6.54
−0.726
1.259
−0.970
1.322
0.624
1.286
−0.183
−0.292
0.077
907285
11467710

(−)-eseroline
18.32
0.123
−1.664
−0.982
0.158
−0.538
−0.565
0.087
0.144
−0.056
907302
11468230

epigallocatechin
20
−1.489
0.559
−1.197
−2.502
−0.531
0.046
−0.238
−0.133
−0.418
907310
11488519

famprofazone
10.6
1.369
−0.725
−1.707
−0.633
0.919
0.525
0.265
0.223
0.297
907320
11467851

hemicholinium
9.64
−0.716
0.385
−1.279
−0.412
1.071
0.136
0.273
0.364
0.047
907335
11467541

lidoflazine
8.14
0.280
−0.611
−0.424
−0.165
0.968
−0.101
−0.703
−0.647
−0.679
907366
11467529

lorglumide
8.7
−0.989
0.392
0.105
−0.220
0.174
0.058
−0.281
−0.423
0.057
907370
11468063

dizocilpine
18.08
0.028
−0.120
−0.772
−0.328
0.684
−0.006
−0.530
−0.557
−0.409
907387
11467257

meprylcaine
17
−0.674
0.647
−1.775
−0.319
0.180
0.336
−0.500
−0.470
−0.480
907413
11468212

nisoxetine
14.74
0.290
−0.479
0.123
0.268
−0.042
−0.937
0.422
0.277
0.636
907434
11468058

pirenperone
10.16
0.385
0.486
−1.310
−0.314
0.470
−0.623
−0.417
−0.337
−0.502
907463
11467679

pirenperone
20
−0.167
1.471
0.205
0.099
0.890
0.319
0.181
0.148
0.254
907463
11489496

(−)-quinpirole
18.24
0.267
0.316
−0.818
−0.447
−0.410
0.222
−0.334
−0.175
−0.598
907479
11468241

tracazolate
13.14
1.005
1.151
−1.205
0.090
1.591
0.440
0.363
0.356
0.295
907524
11468124

telenzepine
10.8
−0.672
−0.155
−1.150
0.033
−0.046
0.023
0.093
0.232
−0.206
907526
11467451

tremorine
20.8
0.408
1.262
−0.389
−0.283
1.072
0.670
0.500
0.700
−0.040
907527
11467479

isotretinoin
13.32
−0.793
0.181
−1.870
−0.022
−0.287
−0.301
1.064
0.989
1.007
1000009
11467404

emetine
20
−1.392
−0.323
−3.535
1.463
−3.162
−0.191
−0.052
1.934
−4.145
1000036
11487888

amiloride
17.42
−0.180
2.179
−0.998
−0.350
0.689
0.137
0.202
0.378
−0.233
1000042
11467155

amiloride
20
−1.067
−1.069
−1.763
−0.880
1.523
0.965
−0.626
−0.618
−0.570
1000042
11487934

paclitaxel
20
0.528
0.812
−0.628
−0.106
−1.967
−1.583
1.683
1.916
0.861
1000045
11488688

bepridil
10.92
−0.391
−0.405
−1.164
−0.821
1.695
0.541
0.316
0.226
0.450
1000048
11467516

bepridil
20
0.890
0.753
−0.802
−0.687
1.217
−0.436
−1.443
−1.250
−1.563
1000048
11488717

gramicidin
20
−3.206
−4.404
−3.832
−3.957
−2.491
−3.179
−1.904
−1.890
−1.510
1000054
11488892

verapamil
8.8
0.905
0.254
−0.022
−0.040
0.124
0.128
−0.024
0.178
−0.465
1000056
11467289

verapamil
20
0.686
−0.638
−1.004
−0.385
1.279
0.053
−0.812
−1.037
−0.159
1000056
11489556

yohimbine
20
−0.411
0.317
−1.180
−0.854
−0.067
0.135
−0.766
−0.464
−1.253
1000060
11488482

amethopterin
8.8
−0.619
0.459
−2.015
−1.117
0.785
−0.343
−0.232
−0.194
−0.264
1000064
11467521

cepharanthine
20
−1.186
0.450
−0.947
−0.297
−0.071
0.057
−1.259
−1.111
−1.332
1000069
11488648

chenodiol
10.18
−0.163
0.190
−1.448
−0.839
0.124
0.090
0.162
0.416
−0.387
1000071
11467433

ifosfamide
15.32
−1.270
0.352
−2.121
−0.547
1.175
0.159
−0.995
−0.833
−1.134
1000080
11467981

rolipram
14.52
−0.116
0.352
−0.854
−0.743
0.302
−0.367
0.476
0.693
−0.077
1000092
11468072

rosiglitazone
20
−0.908
−0.023
−0.990
−0.352
0.382
−0.121
−0.066
0.023
−0.165
1000093
11489057

simvastatin
9.56
−0.166
−2.986
−3.288
0.101
−1.761
−2.713
−0.039
−0.322
0.550
1000094
11468013

simvastatin
20
−1.051
−3.923
−2.644
0.240
−1.276
−1.750
−0.310
−0.448
0.062
1000094
11489487

tetramisole
19.58
−0.035
0.468
−0.507
−0.712
1.088
0.209
−0.045
0.000
−0.124
1000096
11467693

protoporphyrin IX
20
−1.308
0.421
−2.485
−1.307
0.321
−0.180
−0.457
−0.215
−0.792
1000104
11488832

bezafibrate
11.06
−0.864
−0.822
−0.802
−0.364
1.462
0.802
0.408
0.337
0.472
1000105
11467526

bezafibrate
20
−1.167
0.337
−1.393
−0.762
0.861
−0.066
−0.500
−0.137
−1.168
1000105
11488738

praziquantel
12.8
0.677
0.696
0.160
0.110
1.420
−0.166
0.689
0.665
0.615
1000106
11467408

praziquantel
20
−0.918
0.739
−0.219
0.901
0.518
−0.447
−0.134
−0.249
0.130
1000106
11489104

norethindrone acetate
20
−0.119
0.055
−1.400
−0.734
0.393
0.140
0.510
0.640
0.260
1000107
11488879

nadide
20
−0.381
0.549
−1.173
−0.397
1.019
0.126
0.127
0.140
0.152
1000108
11488872

vidarabine
20
−0.817
0.064
−1.227
−0.923
0.451
−0.469
−0.768
−0.785
−0.581
1000109
11489152

isoreserpine
20
1.421
0.495
0.926
−0.748
0.869
0.366
0.194
0.131
0.306
1000110
11489586

biotin
20
−0.621
0.477
−0.488
0.035
0.518
−1.123
0.491
0.376
0.636
1000111
11489326

colforsin
20
0.685
0.921
0.699
−0.647
0.064
−0.130
−1.181
−0.680
−1.990
1000112
11488687

chloroquine
12.5
0.169
−0.540
−1.509
−0.791
0.887
−0.119
−0.191
−0.173
−0.184
1000114
11467696

chloroquine
20
−0.225
−1.253
−2.252
−1.109
1.504
−0.096
0.087
−0.013
0.203
1000114
11487943

rauwolscine
11.28
0.696
1.591
−0.519
−1.075
0.835
−1.218
0.129
0.398
−0.433
1000115
11467725

rauwolscine
20
0.279
0.379
−0.143
−0.092
0.697
0.671
0.099
0.202
−0.150
1000115
11488686

warfarin
20
−0.573
−0.390
−1.607
−0.869
1.144
0.267
0.117
−0.040
0.411
1000116
11488751

progesterone
20
−0.149
−0.703
0.211
0.803
2.274
0.069
−0.741
−0.876
−0.330
1000117
11489115

pseudoephedrine
20
−0.852
0.262
−0.875
−0.687
0.210
0.554
−0.075
−0.171
0.130
1000118
11489119

retinol
20
0.969
0.236
−0.374
0.314
−0.098
−0.791
−0.028
−0.119
0.167
1000121
11489266

cinchonidine
20
0.224
−0.165
0.142
−0.515
1.788
−0.839
0.395
0.392
0.304
1000122
11488535

triamcinolone diacetate
20
0.245
−0.873
0.334
−0.048
−0.125
−0.519
0.272
0.003
0.751
1000123
11488775

atropine sulfate
13.82
−1.258
1.555
−1.107
−0.388
0.338
0.071
0.362
0.481
0.057
1000124
11467713

atropine
20
0.144
−0.142
−0.973
−0.261
1.677
1.709
−0.046
−0.072
−0.036
1000124
11487910

chenodiol
20
−0.576
0.331
−1.535
−0.682
1.400
0.378
0.112
−0.055
0.470
1000126
11488430

triamcinolone acetonide
20
−1.108
−0.121
−0.645
−0.532
−0.589
−0.827
−1.180
−1.318
−0.680
1000127
11488659

carbenoxolone
20
−0.985
1.241
−0.858
−0.952
−0.097
1.239
−0.334
−0.181
−0.600
1000129
11488767

testosterone
20
−0.683
0.074
−1.060
0.259
0.727
−0.787
−1.401
−1.296
−1.306
1000133
11489615

cytidine
20
0.026
−0.291
−0.405
−0.557
−0.229
0.658
0.492
0.547
0.354
1000134
11488977

flurbiprofen
16.38
−1.607
0.523
−1.110
−0.349
0.266
−0.058
−0.151
−0.215
0.004
1000135
11468065

flurbiprofen
20
−0.630
0.116
−1.494
−1.110
0.145
−0.011
0.023
0.008
0.123
1000135
11488841

equilin
20
−0.475
0.291
−0.585
−0.681
0.633
0.464
0.464
0.474
0.341
1000136
11488562

ibuprofen
20
−0.496
−0.246
−1.141
−0.112
0.749
0.425
−0.460
−0.408
−0.531
1000138
11487945

moxalactam
7.68
0.045
0.978
−0.992
−0.516
0.917
0.101
−0.167
−0.104
−0.274
1000139
11467967

moxalactam
20
−0.223
0.469
−1.248
−0.553
1.021
0.395
0.344
0.392
0.257
1000139
11488883

aesculin
20
−0.110
0.965
−1.939
−0.533
1.052
0.687
−0.080
0.059
−0.299
1000141
11488392

18alpha-glycyrrhetinic acid
20
0.249
0.392
−1.047
−0.080
1.345
0.126
0.342
0.351
0.295
1000142
11488236

mimosine
20.18
−0.944
−0.168
−0.913
−0.593
0.789
0.344
−0.354
−0.293
−0.415
1000143
11467527

mimosine
20
−0.286
−0.397
−1.208
−0.140
0.352
0.021
−0.133
−0.106
−0.179
1000143
11488472

levofloxacin
20
−0.073
1.037
−0.557
−0.435
0.757
−0.071
0.303
0.352
0.186
1000155
11489492

naproxen
17.38
−0.979
0.098
−1.287
−0.935
0.565
0.344
−0.546
−0.584
−0.413
1000165
11467193

tobramycin
8.56
−0.704
−1.234
−1.211
−0.868
0.653
0.335
−0.251
−0.278
−0.154
1000177
11467692

hyoscyamine
13.82
−0.871
0.018
−0.804
0.167
0.584
0.319
−1.052
−0.909
−1.177
1000200
11467381

(R)-propranolol
15.42
−0.913
−0.657
−0.854
−0.406
−0.010
0.018
−0.292
−0.450
0.073
1000206
11468223

fusidic acid
7.74
−0.475
−0.781
−1.231
−0.238
0.899
0.047
−0.160
−0.276
0.109
1000211
11467538

urosiol
10.18
−0.172
−0.402
−0.103
0.058
0.054
−0.412
0.638
0.447
0.902
1000212
11468106

thyroxine
5.14
0.900
2.161
−0.689
−0.714
−0.304
0.694
−0.769
−0.424
−1.324
1000219
11467551

thyroxine
20
0.805
1.712
−1.486
−0.646
0.259
1.161
−0.838
−0.847
−0.628
1000219
11488389

fluticasone
8
−1.133
−0.825
−0.911
0.243
0.938
−1.313
0.412
0.220
0.717
1000221
11468145

fludrocortisone acetate
9.46
0.352
−0.711
−0.539
−0.314
−0.337
−0.100
−0.536
−0.599
−0.315
1000235
11467429

flurandrenolide
9.16
0.120
0.061
−0.617
0.531
0.656
0.966
0.508
0.490
0.442
1000240
11467793

cefotiam
7.6
1.338
1.785
−0.522
−0.191
−0.450
1.058
−0.329
−0.142
−0.645
1000242
11467630

dexamethasone acetate
9.2
−0.935
−0.334
−0.041
0.478
−0.110
−1.608
0.056
−0.230
0.593
1000246
11467278

aclacinomycin A1
20
−1.848
1.204
−1.542
−1.920
0.586
0.186
−1.653
−1.759
−1.166
1000247
11489750

becanamycin
20
0.295
−0.371
0.002
−0.339
0.623
0.195
0.068
0.170
−0.120
1000253
11488456

ethambutol
19.58
−0.326
1.132
0.669
−0.448
1.772
−1.231
0.624
0.518
0.667
1000260
11467176

beclomethasone
7.68
−0.448
−0.527
−1.896
−0.501
0.634
−0.129
−0.055
−0.152
0.158
1000270
11468003

bromocriptine
6.12
2.123
0.048
−0.409
−0.738
0.237
−0.066
0.150
0.435
−0.491
1000273
11467269

doxorubicin
7.36
−3.833
−4.338
−4.858
−2.782
−3.244
−4.653
−0.420
−1.850
2.569
1000279
11467586

norethindrone
13.4
−0.987
1.253
−0.971
−0.627
0.371
0.903
−0.282
−0.083
−0.624
1000286
11467401

ritodrine
13.92
0.892
−0.401
−0.658
−1.012
1.731
−0.319
0.439
0.459
0.315
1000292
11467497

mometasone
7.68
−0.544
−0.485
−0.899
0.515
0.261
−0.329
0.624
0.642
0.457
1000293
11467720

cefmetazole
8.48
−0.798
−0.622
−1.102
−0.012
0.777
0.363
−0.526
−0.434
−0.603
1000312
11467848

benazepril
20
−0.214
1.249
−1.063
0.132
−0.701
0.877
−0.488
−0.246
−0.856
1000322
11488298

liothyronine
6.14
0.478
0.874
−1.516
−0.507
1.438
−0.017
−0.090
−0.029
−0.200
1000323
11468001

liothyronine
20
−0.337
0.371
−0.990
−0.267
0.645
−0.118
−1.581
−1.758
−0.963
1000323
11489800

strophantine
6.84
0.897
0.392
0.489
−0.432
−0.336
0.295
−0.500
−0.170
−1.073
1000325
11467619

dibekacin
20
1.367
0.050
−1.282
0.289
0.027
0.464
−0.603
−0.522
−0.645
1000338
11489344

cephalexin
11.52
−1.163
0.555
−0.897
−0.568
1.140
0.140
0.062
0.000
0.178
1000342
11467506

dextromethorphan
14.74
−1.339
0.408
−0.580
−0.583
1.381
0.106
0.216
0.202
0.209
1000343
11467507

meropenem
10.44
−0.017
−0.578
−0.190
−0.198
−0.091
−0.519
0.773
0.732
0.697
1000348
11468254

rosuvastatin
20
−0.298
0.668
−0.858
−0.713
0.573
−0.198
−0.017
−0.175
0.377
1000377
11488906

almotriptan
20
0.044
0.944
−1.755
−0.188
0.388
0.905
−0.888
−0.674
−1.113
1000393
11488314

tegaserod
20
−0.414
0.226
−0.521
−0.148
0.945
0.003
−0.339
−0.278
−0.321
1000411
11488916

atovaquone
20
0.141
−0.954
−1.839
−0.627
−0.475
−0.263
0.775
0.478
1.282
1000656
11489481

teniposide
20
−3.245
−5.758
−4.575
−3.373
−1.526
−3.537
−1.760
−2.625
0.375
1000697
11489463

cyclizine
15.02
0.498
0.836
−0.248
−0.355
1.001
0.646
−0.412
−0.325
−0.515
1000807
11467658

cyclizine
20
0.072
1.230
−0.487
−0.793
0.711
0.061
−1.114
−0.822
−1.428
1000807
11488990

miglitol
20
−0.485
0.607
−1.538
−0.529
1.288
0.148
−0.187
−0.315
0.158
1000878
11488323

laudanosine
11.2
−0.259
0.002
−0.873
−0.944
−0.038
0.092
0.056
−0.021
0.190
1000946
11467739

laudanosine
20
−0.500
0.558
−0.349
−0.779
0.292
0.873
−1.200
−0.885
−1.619
1000946
11488479

valdecoxib
20
0.658
2.260
−0.932
0.408
1.164
−1.335
−0.348
−0.381
−0.168
1001030
11488324

avobenzone
20
−0.230
0.492
−0.339
−0.129
0.116
0.098
−0.816
−0.637
−0.979
1001204
11489479

dactinomycin
20
−3.297
−4.046
−4.712
−2.545
−2.743
−4.013
1.193
−0.575
4.709
1001284
11488251

diphemanil
14.36
−0.579
−0.453
−0.489
−0.112
1.826
0.139
0.376
0.332
0.361
1001312
11467227

dirithromycin
20
−0.880
−0.210
−0.816
−0.455
0.753
0.126
−0.035
0.046
−0.154
1001314
11489471

trisodium ethylenediamine tetracetate
20
−0.946
0.328
−1.123
0.474
−0.436
0.392
−0.539
−0.367
−0.829
1001324
11487819

escitalopram
20
1.301
0.837
1.059
−0.425
−0.377
0.752
−0.372
−0.037
−0.946
1001332
11488367

ezetimibe
20
2.411
1.732
−0.377
0.879
−0.183
−0.066
−0.152
−0.147
−0.093
1001346
11488305

gatifloxacin
20
0.995
1.542
−0.531
−0.248
0.452
0.765
0.305
0.357
0.188
1001366
11488303

metaxalone
20
0.239
0.421
−0.973
−0.359
0.377
−0.068
0.167
0.107
0.298
1001451
11488364

monobenzone
19.98
−0.166
−0.012
−0.874
−0.741
0.059
0.289
−0.414
−0.556
−0.052
1001471
11468060

olmesartan medoxomil
20
−0.233
0.783
−1.486
−0.603
−0.320
0.612
−0.497
−0.468
−0.407
1001491
11488322

oxcarbazepine
20
1.186
1.316
−0.752
0.049
0.052
0.568
−0.838
−0.699
−0.921
1001496
11488299

perindopril erbumine
20
−1.461
1.120
−1.318
−0.841
1.294
0.540
−0.410
−0.468
−0.132
1001518
11488924

fenamisal
20
−0.505
0.548
−1.690
−0.495
1.273
0.492
0.371
0.145
0.804
1001523
11488255

podophyllotoxin
9.66
−0.077
−0.405
−1.865
−0.902
−1.401
−1.416
1.189
1.598
0.118
1001531
11467930

podofilox
20
0.789
−0.716
−1.507
−0.212
−1.436
−0.487
2.274
2.534
1.280
1001531
11488694

tannic acid
20
0.979
1.307
−1.257
−4.214
−1.385
0.416
0.778
0.673
0.881
1001621
11488359

torsemide
11.48
−0.063
−0.620
−0.196
0.218
−0.076
0.826
−0.148
−0.282
0.151
1001638
11468178

torsemide
20
−0.180
0.707
−0.787
−0.536
0.679
−0.369
0.055
0.048
0.111
1001638
11488958

tocopherol
9.28
−1.090
0.824
−1.285
−0.794
−0.564
0.977
−0.714
−0.508
−0.996
1001661
11467552

(S)-(−)-atenolol
15.02
0.012
0.476
−0.552
0.396
−0.554
0.030
−0.280
−0.224
−0.357
1001857
11468101

(R)-(+)-atenolol
15.02
−0.846
−0.351
−1.053
−0.573
1.639
−0.033
−0.106
−0.170
0.053
1001858
11467684

acetylcysteine
20
−0.303
−0.172
−1.437
0.809
0.885
0.402
1.142
1.107
0.920
1001897
11487902

epicatechin
20
−1.657
0.915
−1.727
−2.362
0.513
−0.087
−0.903
−0.887
−0.771
1001923
11488491

epiandrosterone
13.78
−1.401
0.361
0.386
0.515
0.723
−1.183
0.911
0.882
0.791
1001924
11467588

flupentixol
9.2
1.078
0.634
0.369
0.364
1.219
0.933
0.320
0.188
0.521
1001939
11467488

gelsemine
12.4
−0.066
0.190
−1.414
−0.678
1.248
0.289
0.178
0.274
−0.062
1001945
11467810

huperzine A
20
−1.231
0.388
−1.723
−0.628
0.302
−0.152
−0.618
−0.549
−0.653
1001954
11488651

methylprednisolone, 6-alpha
10.68
−0.893
−0.062
−0.968
0.330
0.622
−1.075
0.382
0.331
0.419
1001967
11467427

oxprenolol
15.08
0.312
0.436
0.479
−0.842
−0.060
0.047
−0.060
0.047
−0.283
1001977
11468205

1R,2S-phenylpropylamine
20
−0.684
0.610
−1.501
−1.027
0.690
−0.340
1.123
1.182
0.832
1001994
11488332

shikimic acid
20
−0.210
−0.054
−0.775
−0.574
0.752
−0.575
0.390
0.358
0.393
1002002
11489324

triamcinolone
10.14
−1.198
−0.030
0.109
−0.005
0.391
−1.483
0.019
−0.199
0.424
1002008
11467268

vigabatrin
30.96
1.247
1.232
−1.673
−0.961
1.259
1.011
−0.999
−0.819
−1.173
1002022
11467649

zimelidine
12.6
−0.256
0.669
−1.241
−0.299
0.451
0.133
−0.638
−0.501
−0.837
1002029
11467240

perseitol
20
−1.138
0.707
−0.276
−0.981
1.184
0.652
−0.400
−0.515
−0.054
1002679
11489572

hydroxytoluic acid
20
−0.105
0.802
0.548
−0.525
0.821
1.179
0.651
0.570
0.627
1002775
11487967

phenylbutyrate
20
−0.302
0.550
−0.567
−0.133
1.253
−0.262
−0.397
−0.361
−0.359
1002855
11488326

fenbutyramide
20
0.675
1.115
−0.675
−0.485
0.163
0.580
−1.233
−1.228
−0.971
1002856
11488308

thymoquinone
20
−0.503
0.856
−0.212
−0.361
0.641
−0.765
−0.569
−0.501
−0.617
1003215
11488516

eudesmic acid
20
−0.436
0.802
−0.440
−0.769
0.640
0.841
−0.405
−0.402
−0.341
1003514
11488607

phenylacetohydroxamic acid
20
−0.682
−0.170
−1.861
−0.849
0.883
0.136
0.062
0.055
0.101
1003535
11489532

larixinic acid
20
−0.702
0.333
−1.835
−0.810
0.179
0.132
−1.054
−1.119
−0.673
1003823
11489611

N-methylanthranilic acid
20
−0.146
−0.082
−0.120
−1.181
0.967
0.299
−0.385
−0.179
−0.683
1004713
11489732

metacetamol
20
−1.338
0.154
−2.107
−0.578
0.692
0.182
−0.259
−0.114
−0.460
1004889
11488333

benzanthrone
20
0.277
0.108
−1.435
−1.288
1.609
−0.308
0.690
0.880
0.155
1005991
11488582

5,7-dihydroxy-4-methylcoumarin
20
−0.483
1.206
−0.741
−1.609
0.687
0.189
0.525
0.710
0.052
1006104
11489172

purpurin
20
−1.205
−0.402
−2.248
−2.389
1.584
1.010
0.375
0.336
0.331
1007083
11487853

chrysanthemic acid
20
−0.582
0.602
−0.735
−0.366
−0.121
0.675
−0.437
−0.489
−0.222
1007364
11489607

thonzonium bromide
7.82
−1.864
−2.454
−1.328
−0.236
−1.390
−1.152
0.868
0.997
0.413
1007994
11468073

pentylenetetrazole
28.94
1.091
1.642
−1.013
−0.228
0.069
1.064
−0.462
−0.422
−0.495
1008060
11467310

pentetrazole
20
0.523
0.164
−0.423
0.010
−0.535
0.949
0.382
0.373
0.386
1008060
11488937

diffratic acid
20
0.620
1.210
−2.807
0.281
1.373
0.318
0.959
0.666
1.344
1008178
11488546

dibenzoylmethane
20
−0.350
−1.193
−1.719
−0.031
0.846
−0.484
−0.553
−0.956
0.330
1008492
11487854

O-veratraldehyde
20
−1.299
−1.020
−2.796
0.347
−0.925
−1.483
−0.478
−0.568
−0.245
1008535
11489780

mandelic acid, methyl ester
20
0.277
−0.088
−0.364
−0.284
0.074
0.835
−0.312
−0.147
−0.650
1008719
11487998

alloxan
20
0.483
1.409
−0.552
−0.634
0.080
0.678
0.373
0.362
0.358
1009258
11488347

alizarin
20
−0.562
1.648
−0.981
−2.407
1.154
0.211
0.600
0.667
0.401
1009294
11488213

hematein
20
−0.357
−0.036
−1.726
−1.215
0.835
0.132
−0.042
−0.084
0.086
1009367
11488428

veratric acid
20
0.049
−0.216
−1.025
−0.545
0.049
−0.013
0.147
0.295
−0.111
1009654
11488898

anthraquinone
20
0.201
0.593
−0.987
0.865
0.859
0.975
−0.476
−0.435
−0.431
1009851
11488221

mucic acid
20
−0.614
0.362
−1.136
−0.633
−0.025
0.379
−0.939
−1.022
−0.592
1009973
11489270

chloranil
20
−4.795
−8.532
−6.360
−4.051
−3.428
−5.311
−0.841
−2.448
2.504
1010201
11487840

diphenylurea
20
1.065
−1.101
0.770
−0.598
−0.022
−0.392
0.472
0.423
0.510
1010251
11489654

lawsone
20
−0.304
0.103
−0.834
−0.260
−0.103
−0.273
0.227
0.240
0.163
1010348
11489322

brazilin
20
−1.426
1.655
−1.218
−0.602
−1.481
−0.848
−0.672
0.001
−1.884
1010376
11488198

haematoxylin
20
−1.044
0.382
−1.335
−1.035
0.225
0.028
0.094
0.337
−0.395
1010377
11488415

coumarin
20
−0.167
0.494
−0.805
−0.518
0.740
0.232
−0.132
−0.217
0.011
1010471
11488119

trichlorfon
15.54
1.232
0.239
−1.804
−0.493
−0.740
0.081
−1.085
−0.845
−1.404
1010605
11467199

apiole
20
0.028
0.655
−1.184
−0.188
1.294
0.460
0.591
0.611
0.470
1010689
11488235

1,4-naphthoquinone
20
−5.494
−8.116
−6.183
−3.902
−3.491
−4.549
−2.220
−2.490
−1.260
1011006
11488297

apomorphine
20
−0.852
−1.905
−2.279
−1.416
−0.457
0.044
0.302
0.401
−0.037
1011303
11487958

4-methylesculetin
20
−0.301
0.901
−2.063
−0.362
1.255
0.262
−0.300
−0.190
−0.430
1011559
11488433

tryptophan
20
−0.209
0.143
−1.175
−0.878
0.517
0.200
0.239
0.190
0.360
1012497
11488918

butylparaben
20.6
−0.445
1.180
−0.832
−0.442
0.648
0.379
−1.142
−1.062
−1.095
1012530
11468042

norcantharidin
20
−0.657
−0.697
−3.125
0.478
0.510
−1.419
−0.399
−0.196
−0.699
1013144
11489499

adenine
20
−0.236
0.732
−1.384
−0.283
0.030
0.146
−1.374
−1.354
−1.114
1013195
11488399

xanthone
20
0.474
−1.238
−0.928
−0.078
0.112
0.526
−0.303
−0.066
−0.774
1013706
11487868

indole-2-carboxylic acid
20
0.090
−0.861
−0.726
−0.283
−0.079
0.237
0.464
0.549
0.149
1014792
11487837

D-arabitol
20
−1.158
−0.213
−0.597
−0.705
0.316
0.521
−1.273
−1.307
−0.907
1014978
11489562

adonitol
20
−0.469
−0.242
−1.425
−0.761
0.234
0.850
−0.211
−0.210
−0.128
1014978
11489610

gramine
22.96
−0.958
−0.640
−0.947
−0.451
0.657
−0.212
0.176
−0.333
1.191
1014994
11467777

xanthoxylin
20
−1.210
0.423
−1.069
−0.651
0.420
0.269
0.110
0.131
0.085
1015281
11488279

riboflavin
10.62
0.029
0.364
−1.380
−0.767
1.150
0.109
−0.002
0.195
−0.388
1015808
11467782

aminolevulinic acid
20
−0.207
0.354
−0.846
−0.065
0.035
0.213
−0.105
0.030
−0.308
1015899
11489478

rhamnetin
20
−1.211
1.672
−0.975
0.717
0.228
1.561
−0.657
−0.304
−1.273
1016582
11488458

gallic acid
20
−1.517
−0.490
−1.991
−1.311
0.281
−1.678
0.102
0.279
−0.224
1016781
11488215

diallyl sulfide
20
−1.284
−0.397
−1.776
−0.930
1.047
−0.217
0.210
0.264
0.047
1017172
11488653

6-aminonicotinamide
20
−0.531
−1.410
−0.525
0.082
0.871
0.520
−0.386
−0.355
−0.340
1017318
11489525

osajin
20
−1.424
−2.997
−2.351
−2.214
2.139
−2.625
−1.054
−0.943
−1.128
1017609
11487991

phenformin
19.48
0.372
−0.240
−1.696
−0.517
−0.545
0.241
0.616
0.870
−0.059
1018627
11467327

2,6-dimethoxyquinone
20
−5.784
−7.615
−5.944
−3.903
−4.010
−3.043
−1.600
−2.620
0.860
1019365
11488597

2-methyl gramine
20
−2.419
−2.788
−2.058
0.371
−1.879
−3.013
−0.685
−0.660
−0.616
1019607
11488506

methylatropine
13.14
0.416
0.651
1.098
0.249
1.762
−0.661
0.508
0.407
0.603
1019709
11468048

homochlorcyclizine
12.7
−0.348
−0.769
−1.521
−0.629
0.579
−0.789
−0.644
−0.711
−0.387
1019722
11467431

metameconine
20
0.050
−0.214
−1.318
−0.277
0.658
0.486
−0.728
−0.437
−1.128
1019872
11489718

phenacylamine
20
−0.497
0.572
−1.279
−0.234
0.384
0.088
−1.272
−1.327
−0.965
1019888
11489809

benzylhydrazine
20
−0.105
1.031
−1.343
−0.316
0.768
0.786
−0.681
−0.342
−1.160
1020088
11489039

esculetin
22.46
−1.108
−0.015
0.611
0.129
−0.636
0.134
−0.568
−0.501
−0.609
1020463
11468088

esculetin
20
−0.918
0.401
−1.955
0.086
0.194
−1.251
−0.984
−0.793
−1.149
1020463
11488402

alpha-mangostin
20
0.984
0.277
0.526
−2.090
1.261
−1.053
−0.012
−0.097
0.197
1020994
11489436

ethamsylate
21.04
−1.122
−0.260
−0.708
−0.824
0.970
0.142
0.117
0.229
−0.159
1022844
11468163

3-acetylcoumarin
21.26
0.165
1.143
−0.293
−0.177
−0.010
0.650
0.394
0.502
0.085
1022907
11468039

osthol
20
1.353
1.846
−0.371
1.293
0.745
0.452
−0.599
−0.248
−1.221
1023016
11488539

carbarsone
15.38
0.601
0.661
−1.304
−0.622
−0.236
0.575
0.175
0.128
0.241
1023517
11467561

4-hydroxy-6-methylpyran-2-one
20
−0.952
0.095
−1.112
−0.736
0.314
−0.316
0.182
0.294
−0.135
1024489
11489794

6,7-dimethoxy-1-methyl-1,2,3,4-
19.3
−0.146
−0.022
−1.532
−0.719
0.831
0.319
0.168
0.197
0.080
1024517
11467680

tetrahydroisoquinoline

salsolidine
20
−0.667
0.104
−1.413
−0.706
0.269
−0.007
−0.837
−0.765
−0.779
1024517
11489442

(D,L)-tetrahydroberberine
11.78
0.186
−1.024
−2.007
−0.541
−0.601
0.408
0.475
0.372
0.572
1025381
11467820

2-aminobenzenesulfonamide
23.22
0.130
0.688
−0.277
−0.580
0.280
0.044
0.721
0.549
0.921
1025776
11468061

chrysophanol
20
−0.004
0.285
−2.906
−1.225
0.291
0.561
−1.273
−1.181
−1.271
1025940
11487859

2-hydroxy-3,4-dimethoxybenzoic acid
20
−1.147
1.210
−0.857
0.908
0.261
0.331
−1.003
−1.020
−0.832
1026119
11489737

2-acetylpyrrole
20
−0.920
0.397
−1.050
−0.692
0.716
−0.009
−0.122
−0.067
−0.253
1029168
11489772

safrolglycol
20
−0.657
0.236
−1.436
−0.947
0.344
−0.051
−0.539
−0.367
−0.796
1029487
11488499

2,6-dihydroxy-4-methoxytoluene
20
−0.805
0.068
−1.048
−0.565
0.139
0.267
−0.918
−0.887
−0.752
1029490
11489619

moroxidine
23.36
−0.140
0.676
−0.643
−0.722
−0.040
1.127
−0.450
−0.245
−0.819
1029858
11467232

tropine
28.32
−1.554
0.953
−0.558
−0.370
−0.114
−0.175
0.244
0.350
−0.030
1029881
11468225

4-methyldaphnetin
20
−1.167
0.765
−1.183
−0.519
−1.229
0.445
−0.735
−0.866
−0.293
1030891
11488137

citrulline
20
−0.129
1.090
−1.207
0.077
0.307
0.910
0.449
0.509
0.230
1031375
11489187

4-acetoxyphenol
20
−0.142
0.982
−0.987
−1.179
−0.565
−0.347
−0.615
−0.687
−0.286
1031842
11488961

cresopyrine
20
0.505
0.240
−0.635
−0.345
−0.146
0.617
0.111
0.041
0.279
1032444
11488371

flavanone
20
−1.078
−0.294
−0.639
−0.733
−0.221
−0.102
−0.483
−0.591
−0.224
1032994
11488021

tangeritin
20
1.230
−0.141
−0.567
0.380
1.163
0.951
−0.302
−0.228
−0.355
1034727
11489514

harmane
21.96
−0.359
−0.385
−1.138
0.074
1.285
−0.307
−0.324
−0.334
−0.227
1035065
11467768

phloracetophenone
20
−0.384
−0.673
−0.760
−0.710
1.330
0.059
−0.393
−0.613
0.087
1035250
11489805

3-hydroxyflavone
20
−5.146
−6.482
−4.941
−2.910
−3.665
−4.110
−2.484
−3.582
0.181
1036721
11489208

pseudopelletierine
26.1
−0.946
0.266
−1.231
−0.356
0.441
0.326
0.171
−0.085
0.668
1039072
11467773

3-acetamidocoumarin
19.68
0.050
2.085
0.646
0.367
−0.180
0.627
0.143
0.304
−0.226
1040327
11468117

3-methoxycatechol
20
−1.592
−0.649
−1.577
−1.022
−1.153
−0.541
−1.331
−1.126
−1.437
1040795
11489733

orthothymotinic acid
20
−1.810
−0.013
−1.403
−0.822
1.518
0.397
0.067
−0.220
0.693
1041649
11488254

harmol
20.18
−0.149
−0.557
−2.086
−0.469
0.651
1.084
−0.770
−0.801
−0.558
1043296
11467760

harmol
20
−0.412
0.713
−2.550
0.020
−0.017
0.409
−0.121
−0.506
0.738
1043296
11488320

3-hydroxycoumarin
20
−0.257
0.054
−1.305
−0.084
−0.551
0.288
−0.026
0.031
−0.156
1044412
11488621

5-chloroindole-2-carboxylic acid
20
−1.114
0.601
−1.288
−0.628
0.053
0.477
−0.573
−0.745
−0.072
1044852
11488329

diperodon
10.06
0.447
−0.347
−0.253
−0.279
1.342
−0.532
−0.681
−0.538
−0.832
1045066
11467448

djenkolic acid
20
−0.063
0.238
−0.410
−0.248
0.019
−0.003
−0.940
−0.811
−0.971
1045072
11489605

nobiletin
20
1.191
0.037
−1.693
0.397
0.826
0.396
1.029
1.252
0.417
1045397
11489513

norharman
20
0.277
1.571
−1.235
−0.056
1.683
−0.972
0.359
0.502
0.055
1048361
11488404

6-methoxyharmalan
18.66
0.431
−0.280
−0.542
−0.687
0.951
0.448
0.030
−0.083
0.253
1048750
11467769

stictic acid
20
0.165
−0.832
−1.355
−0.780
1.202
0.938
0.547
0.809
−0.163
1049466
11488123

atranorin
20
−1.280
−1.384
−1.246
−0.614
0.608
0.873
−0.474
−0.617
−0.046
1049467
11489565

asarylaldehyde
20
−0.477
0.432
−0.959
−0.981
0.951
0.429
1.067
1.084
0.888
1050335
11488202

ononetin
20
0.642
0.382
−0.196
−0.079
0.130
−0.250
0.367
0.547
−0.089
1050602
11488624

1,3,5-trimethoxybenzene
20
−0.674
0.179
−2.053
−0.641
2.302
0.545
−0.387
−0.307
−0.432
1050711
11488242

psoromic acid
20
0.147
−1.096
−1.499
−0.734
−0.599
0.397
−1.114
−1.069
−1.037
1051460
11488030

salsoline
20
−0.350
0.448
−0.467
−0.964
0.862
−0.470
0.335
0.145
0.694
1052338
11488356

oxalamine
16.3
−0.255
−0.739
−1.880
−0.635
1.404
0.631
−0.509
−0.379
−0.686
1052436
11467974

visnagin
20
−0.893
−0.777
−1.716
−0.509
0.098
−0.163
0.231
0.116
0.463
1052459
11489612

quercetin tetramethyl ether
20
0.552
1.402
−0.354
1.428
0.442
0.181
0.147
0.331
−0.277
1053058
11488527

3-hydroxy-3′,4′-dimethoxyflavone
20
−0.631
−0.318
−2.254
2.225
−0.579
−0.230
−0.956
−0.845
−0.968
1053060
11489518

azapropazone
13.32
−0.340
−0.385
−1.289
−0.533
1.003
0.418
−0.064
−0.094
0.005
1053328
11468151

eupatorin
20
−1.135
0.603
−1.919
−0.552
1.569
0.347
−0.796
−0.722
−0.751
1054271
11488272

evoxine
11.52
−0.309
0.694
−1.383
−1.248
1.984
0.144
−0.117
−0.110
−0.113
1054504
11467813

evoxine
20
−0.487
−0.535
−1.076
−0.029
0.688
0.145
−0.021
0.107
−0.239
1054504
11489441

skimmianine
15.42
−0.273
0.728
−0.365
−0.046
1.278
−1.263
−0.279
−0.279
−0.221
1054505
11467816

ornidazole
18.22
0.769
0.204
−0.577
−0.509
0.241
0.878
−0.478
−0.278
−0.833
1054660
11467312

lobelanidine
11.78
−0.257
0.582
−1.552
−1.028
0.549
0.816
0.048
−0.045
0.222
1054667
11467730

coralyne
10.98
0.005
0.814
−0.101
−2.821
0.173
0.283
−0.968
−0.630
−1.490
1055132
11467579

coralyne
20
−1.233
0.221
−2.193
−2.677
0.998
0.451
−0.286
−0.233
−0.311
1055132
11488421

3-hydroxy-DL-kynurenine
17.84
0.692
0.967
−0.405
−0.472
−0.323
0.355
0.140
0.292
−0.205
1055159
11467599

pterin-6-carboxylic acid
20
0.712
0.141
−0.742
−0.307
0.146
0.484
0.124
0.349
−0.316
1055442
11489637

calycanthine
11.54
−0.517
0.362
−1.454
−1.253
0.523
0.347
0.112
0.078
0.157
1056553
11467743

macluroxanthone
20
−2.337
−5.271
−3.386
−3.197
−2.521
−2.511
−2.766
−2.306
−3.136
1057125
11488247

cyclopenthiazide
10.52
−1.155
−0.565
−0.429
−0.719
0.728
−0.087
0.614
0.653
0.410
1057366
11468142

3-desmethyl-5-deshydroxyscleroin
20
−0.001
0.557
−0.927
0.336
1.578
−0.316
−0.723
−0.828
−0.429
1059133
11488006

quercetin pentamethyl ether
20
−1.273
−0.637
−1.039
−0.734
0.307
−0.112
−0.981
−0.814
−1.088
1060118
11489620

cephalotaxine
20
−0.289
0.588
−1.758
−0.937
0.357
0.296
−0.741
−0.760
−0.522
1064620
11488391

N-acetylaspartic acid
22.84
0.285
0.133
−0.942
−0.433
0.365
0.638
−0.394
−0.222
−0.674
1064663
11467563

albizziine
20
−0.570
−0.117
−1.129
−0.196
0.966
0.396
−0.230
−0.333
0.075
1065857
11488275

niridazole
18.68
−0.675
−0.149
−0.505
−0.223
0.114
−0.531
−0.478
−0.561
−0.206
1067495
11467617

orsellinic acid, ethyl ester
20
−0.154
0.432
−1.081
−0.109
0.973
−0.722
0.444
0.207
0.886
1071570
11488206

kainic acid
20
−1.056
0.683
−1.319
−0.892
1.417
0.379
−0.128
−0.130
−0.022
1072288
11489064

denatonium
12.28
−0.620
1.887
−0.109
0.811
−0.165
1.822
−0.028
−0.066
0.037
1073908
11468109

homosalate
15.24
−0.562
0.298
0.370
0.753
−0.480
−1.151
0.436
0.372
0.469
1076027
11468238

synephrine
23.92
−0.879
−0.555
−0.367
0.030
0.028
−0.727
−0.297
−0.489
0.143
1076620
11468236

tiletamine
17.92
−0.944
−0.269
−0.859
−0.227
0.199
0.143
0.380
0.315
0.437
1077199
11468170

benperidol
10.48
1.359
0.963
−0.768
−0.233
0.541
0.787
0.044
0.153
−0.186
1077918
11467632

azaperone
12.22
0.447
−0.125
0.603
−0.221
−0.077
−0.184
1.495
1.429
1.323
1078453
11468265

azaperone
20
−0.674
0.122
−0.529
0.011
0.829
−0.129
−0.600
−0.486
−0.633
1078453
11489066

4-hydroxyantipyrine
19.58
−0.437
0.266
0.102
−0.265
0.948
−0.045
0.934
0.863
0.852
1079457
11467178

enilconazole
13.46
−0.521
3.446
−0.330
1.113
1.262
0.594
−0.326
−0.223
−0.488
1081653
11468111

betamipron
20
−1.385
−0.653
−2.165
−0.788
0.587
0.275
−0.165
−0.296
0.173
1082254
11488250

dehydrorotenone
20
−0.381
0.836
−1.046
0.884
0.804
−0.674
0.452
0.554
0.118
1082584
11489746

palmatine
11.36
0.142
0.416
−0.898
−1.653
0.543
0.129
0.664
0.250
1.379
1084508
11467727

palmatine
20
−1.219
0.461
−1.002
−1.380
1.352
0.145
0.104
−0.242
0.838
1084508
11488424

isopimpinellin
20
0.191
−0.582
−0.707
0.188
0.846
0.230
0.091
−0.190
0.580
1086162
11488124

ethyl 1-benzyl-3-hydroxy-2-oxo[5h]pyrrole-4-
20
0.379
0.141
0.969
−0.204
0.154
0.194
−0.659
−0.276
−1.273
1087705
11489647

carboxylate

chloropyramine
13.8
1.140
1.585
−0.445
−0.970
−0.336
1.386
0.070
0.212
−0.235
1088922
11467955

nimustine
20
0.321
0.010
−0.349
−0.211
−0.345
−0.429
0.203
0.345
−0.148
1089854
11488693

amidopyrine
17.3
0.691
0.989
−0.051
−0.496
−0.776
0.748
0.388
0.531
−0.016
1090166
11467236

lecanoric acid
20
0.847
−0.316
−0.302
−0.852
−0.075
0.690
−0.616
−0.512
−0.770
1090422
11488027

physcion
20
−0.196
1.210
−1.100
−0.413
0.033
0.978
−0.831
−0.967
−0.352
1090658
11488319

clopidol
20
−0.449
1.053
−1.395
−0.542
1.696
0.448
−0.313
−0.107
−0.716
1090918
11487834

aminopterin
20
−0.825
0.979
−1.547
−1.020
0.719
0.484
−1.396
−0.989
−1.963
1091345
11488709

rhetsinine
20
0.348
−0.961
−0.895
0.093
0.452
0.068
−0.025
0.218
−0.479
1091368
11489477

acetopromazine
12.26
0.557
0.746
−1.188
−0.923
0.262
0.844
0.080
0.182
−0.142
1092107
11467724

4-methoxydalbergione
20
0.495
0.730
−0.789
−0.797
−0.527
0.113
−0.989
−0.932
−0.917
1092958
11488470

N-acetylproline
20
−0.198
0.707
−1.007
−0.132
0.241
0.493
−0.838
−0.635
−1.129
1094519
11487829

methacholine
24.96
−1.105
−0.595
−0.798
0.334
0.966
−0.572
−0.717
−0.666
−0.687
1094620
11467907

ocadecylphosphocholine
20
−0.414
−0.842
−0.206
−0.631
0.165
−1.201
−0.664
−0.516
−0.831
1095029
11489305

fluoxetine
12.94
0.060
−0.919
−1.384
−0.269
0.705
−3.551
−0.659
−0.480
−0.895
1095093
11467659

fluoxetine
20
−2.466
−5.742
−3.524
2.634
−1.363
−0.156
−0.258
−0.302
−0.082
1095093
11489474

triadimefon
20
−0.420
0.051
−1.650
−0.530
0.592
0.286
−0.142
−0.198
0.047
1099044
11489523

lonchocarpic acid
20
0.014
0.318
−0.950
0.105
−0.633
0.826
0.049
−0.074
0.315
1099943
11489578

bupropion
16.68
−0.417
1.254
−0.230
0.064
0.168
−0.733
−0.390
−0.258
−0.590
1101055
11467397

bupropion
20
−0.492
−1.081
−0.855
−0.491
0.660
0.618
−1.654
−1.842
−0.911
1101055
11489475

eupatoriochromene
20
0.170
0.533
−0.911
−0.829
−0.059
0.627
−0.339
−0.173
−0.633
1107153
11488487

cuneatin methyl ether
20
0.399
0.893
−0.485
1.153
−0.034
0.951
−0.796
−0.785
−0.619
1109169
11488217

paeonol
20
0.551
0.203
−0.944
−0.424
0.103
0.306
−0.667
−0.613
−0.694
1110410
11489797

imperatorin
20
−0.193
0.764
−0.883
−0.218
0.942
0.406
0.465
0.434
0.481
1111461
11488192

1-aminocyclobutane carboxylic acid
20
−1.102
−0.120
−1.107
−0.706
0.502
−0.335
−0.522
−0.578
−0.287
1111718
11489292

quinic acid
19.68
0.562
−0.028
−0.586
−0.500
−0.527
0.011
1.086
1.010
1.019
1111897
11468251

herniarin
20
0.366
0.712
−1.164
−0.635
0.295
−0.201
1.569
1.467
1.527
1112402
11488214

pachyrrhizin
20
−0.749
1.109
0.278
1.326
1.322
0.486
0.586
0.428
0.827
1112405
11488226

chelidonine (+)
20
−0.007
−0.075
−2.823
−0.734
−1.009
−0.051
−0.037
−0.059
0.059
1113269
11488401

ethamivan
17.92
0.143
0.416
−0.306
0.296
1.121
−0.159
−0.441
−0.077
−1.089
1113307
11467648

fisetin
20
−0.764
0.456
−0.689
−0.893
0.442
−0.825
−0.131
−0.202
0.120
1113841
11488976

eugenyl benzoate
20
−0.673
−0.145
−0.867
−0.793
0.752
0.427
−1.399
−1.553
−0.770
1114909
11489721

ricinine
24.36
−0.938
−0.040
−1.117
−0.894
1.586
0.333
−0.705
−0.772
−0.425
1115322
11467826

perillyl alcohol
20
−1.426
−0.312
−1.446
−0.071
0.324
−0.770
0.032
0.205
−0.352
1117560
11488654

fraxetin
20
−0.954
0.001
−0.257
−1.390
−0.472
−0.645
−0.248
−0.377
0.108
1119359
11489455

5,7,4′-trimethoxyflavone
20
1.177
0.878
−0.529
0.162
1.187
0.690
0.078
0.107
0.050
1129781
11488287

pirlindole
17.68
0.693
0.741
−0.508
0.845
0.273
0.113
−1.618
−1.645
−1.269
1134931
11468121

prenylamine
12.14
0.666
−0.303
0.783
0.221
0.261
−0.799
−0.105
−0.116
−0.066
1137095
11467708

8-azaguanine
26.3
−1.815
2.211
−3.284
−0.269
−0.702
−0.772
−0.268
0.069
−0.956
1164875
11467149

graveoline
14.32
−0.675
−0.442
−1.868
−1.003
0.781
0.073
0.025
−0.096
0.255
1182082
11467822

albendazole
15.08
−0.402
0.854
−1.894
−0.296
−1.434
−0.280
1.472
1.575
0.963
1185085
11467395

peucedanin
20
−0.128
0.947
−0.535
1.283
0.772
0.025
0.457
0.393
0.474
1204574
11488545

pyrogallin
20
0.735
1.074
−0.276
−1.638
−1.159
0.460
0.111
0.174
0.005
1210108
11488369

doxazosin
8.86
0.032
−0.438
−2.021
−0.510
0.525
−0.349
−0.173
0.130
−0.738
1215118
11468006

lomatin
20
−0.313
−0.024
−1.088
−0.532
0.872
0.292
1.366
1.472
0.873
1216977
11488551

trimethylcolchicinic acid
11.64
0.624
0.665
−0.160
−0.057
2.869
−0.455
0.463
0.316
0.667
1219467
11467728

tolfenamic acid
15.28
−0.486
−0.490
−1.076
−0.393
0.935
0.994
−0.571
−0.655
−0.328
1258696
11467353

tolfenamic acid
20
0.781
1.433
−0.820
0.187
0.019
0.163
−0.743
−0.690
−0.701
1258696
11489262

moricizine
9.36
4.015
1.072
−0.636
−0.488
−0.597
0.506
−1.040
−1.010
−0.920
1267101
11468199

noreleagnine
20
−0.319
0.384
−0.992
−0.406
2.215
0.363
0.483
0.459
0.440
1275107
11489195

fenbendazole
13.36
−1.112
−0.672
−3.590
−0.395
−0.919
−1.263
−0.247
−0.449
0.176
1281686
11467358

ursinic acid
20
−0.339
1.207
−1.373
−0.377
1.168
0.385
−0.879
−1.088
−0.290
1296906
11488549

carteolol
13.68
−0.636
0.272
−1.361
−0.909
0.900
0.284
−0.151
−0.076
−0.273
1300555
11467594

anabasamine
20
0.194
2.169
−0.451
0.626
1.775
0.737
−0.370
−0.320
−0.400
1307902
11488543

4′-methoxyflavone
20
−0.685
−0.937
−2.665
0.985
−0.200
0.099
0.051
0.053
0.033
1308020
11488590

etilefrine
22.08
−0.527
−0.198
−0.290
−0.888
1.151
−0.311
0.681
0.750
0.403
1326779
11468165

gliquidone
7.58
1.017
−0.244
−1.418
−0.322
0.255
0.274
0.110
−0.021
0.348
1327636
11468139

dubinidine
14.52
−0.918
−0.057
−0.592
0.038
−0.014
−0.391
−0.036
−0.151
0.193
1336284
11468233

dictamnine
20
−0.505
−0.316
−1.500
0.535
0.549
0.194
0.702
0.506
1.011
1352641
11488165

trimetazidine
15.02
−0.050
−1.226
−0.803
−0.534
0.607
0.229
0.461
0.474
0.347
1365793
11467697

7,4′-dimethoxyisoflavone
20
1.005
0.478
−1.267
−0.490
0.773
0.261
0.197
0.050
0.413
1372522
11488001

3,7-dihydroxyflavone
20
−0.456
−0.915
−0.312
−2.946
−2.085
0.215
0.095
0.444
−0.600
1386109
11489468

levonordefrin
21.84
−0.087
1.348
−0.710
−1.137
0.294
−0.636
−0.224
−0.166
−0.293
1402956
11467887

nordefrin
20
0.638
0.219
0.166
−0.895
−0.018
−0.951
−0.063
−0.318
0.504
1402956
11489653

ethotoin
19.58
−0.800
−0.485
−1.749
−0.745
1.170
0.248
−0.903
−0.691
−1.157
1424515
11467844

timolol
12.64
0.053
0.107
0.175
−0.146
0.440
−0.362
−0.595
−0.590
−0.481
1428570
11468096

6-benzylaminopurine
17.76
−0.302
0.316
−0.254
−0.549
1.260
0.518
−0.201
−0.258
−0.087
1428839
11467337

ondansetron
13.64
−0.341
1.494
0.145
−0.331
0.719
0.375
−0.572
−0.443
−0.739
1434439
11468206

chlorquinaldol
20
−0.712
0.379
−1.018
−0.765
0.224
0.140
−1.384
−1.357
−1.132
1449108
11488340

azacyclonol
14.96
0.047
0.894
−0.594
−0.633
0.492
0.380
−0.448
−0.532
−0.247
1451360
11467241

pefloxacine
20
−0.589
0.022
−2.114
−0.877
−0.100
0.113
−0.326
−0.406
−0.146
1461079
11487850

1-methylxanthine
20
0.082
0.307
−0.865
−0.093
0.180
0.250
−0.251
−0.248
−0.145
1464728
11489011

trolox
15.98
−0.273
−0.639
−0.669
−0.497
−0.542
−0.441
−0.631
−0.607
−0.555
1470254
11467678

N-hydroxymethylnicotinamide
20
0.760
0.339
0.243
−0.391
0.366
−0.140
0.697
0.811
0.401
1492782
11489013

7,2′-dimethoxyflavone
20
−0.904
2.404
−0.909
1.076
0.306
0.916
−0.346
−0.288
−0.366
1499608
11488140

molindone
14.48
−1.104
−0.132
−0.423
−0.313
0.474
−0.177
1.206
0.870
1.664
1511611
11468183

brompheniramine
12.52
−0.319
−1.424
−1.034
−0.479
−0.401
−1.195
−0.303
−0.163
−0.536
1537011
11467623

brompheniramine
20
−0.583
0.512
−0.648
1.632
0.401
−0.229
0.613
−0.023
1.799
1537011
11489426

7-hydroxy-2′-methoxyisoflavone
20
−0.973
−0.019
−1.654
−0.327
0.478
−0.193
0.704
0.732
0.570
1539748
11488414

foliosidine
13.02
−0.233
−0.060
−1.243
−1.032
2.079
0.419
−0.284
−0.299
−0.202
1540789
11467815

6,4′-dimethoxyflavone
20
−0.838
2.025
−0.935
1.774
0.329
0.916
−0.950
−0.881
−0.864
1552436
11488138

diltiazem
20
−0.542
−0.757
−2.284
−1.479
1.020
0.385
−0.618
−0.403
−0.882
1587004
11489552

thermopsine
20
−0.299
0.109
−0.966
−1.038
−0.198
0.486
−0.583
−0.326
−0.945
1592184
11489443

lupanine
20
−0.176
1.429
−0.156
−0.178
0.560
0.153
0.340
0.178
0.637
1592184
11489505

losartan
20
1.208
0.072
−0.833
−0.886
−0.340
0.081
−0.345
−0.353
−0.223
1606766
11489493

cefamandole
20
0.666
0.897
−0.954
1.278
1.175
0.222
−0.224
−0.374
0.089
1635952
11489813

estradiol benzoate
20
−0.697
0.339
−1.333
−0.644
1.957
0.591
−0.916
−0.629
−1.248
1661997
11488912

sulfachloropyridazine
14.04
−0.675
0.023
−1.776
−0.809
0.928
−0.066
0.119
−0.046
0.438
1668673
11467863

sulfachlorpyridazine
20
−0.951
−0.005
−1.163
−0.362
0.611
0.188
0.033
0.003
0.038
1668673
11489758

3′,4′-dimethoxyflavone
20
0.168
−1.107
−1.294
1.634
0.104
−1.270
0.043
−0.374
0.881
1713087
11488525

pinocembrin
20
0.098
0.289
−1.277
0.000
0.845
−1.513
−0.178
−0.265
0.076
1734308
11489486

boldine
12.22
−1.288
−0.637
−1.026
−0.529
0.060
0.505
−0.367
0.105
−1.253
1737132
11467748

boldine
20
−0.616
0.728
−1.980
−1.070
0.242
−0.754
−0.522
−0.828
0.241
1737132
11488411

biochanin A, dimethyl ether
20
0.667
0.376
−1.779
0.402
0.251
0.227
−0.814
−0.749
−0.753
1864491
11489519

phenethyl caffeate
20
−1.626
−0.517
−2.695
0.387
−2.764
−2.848
−1.698
−1.604
−1.575
1907763
11488635

4-naphthalimidobutyric acid
20
−0.597
−0.403
−0.438
−0.619
1.353
0.276
0.370
0.199
0.693
1913604
11488265

4′-methoxychalcone
20
0.083
−0.085
−0.484
0.178
0.974
−1.182
−0.552
−0.423
−0.734
1913676
11488636

azathioprine
14.42
−0.835
−0.254
−1.407
−0.321
−0.531
0.343
−1.121
−1.320
−0.540
1921128
11467242

nifuroxazide
14.54
−0.395
−0.168
−0.624
−0.629
0.535
0.234
0.138
0.105
0.186
1931603
11467703

hymecromone
20
0.672
0.191
−0.065
−0.521
−0.147
0.214
0.025
0.103
−0.109
1952709
11489585

cefoperazone
20
0.097
0.164
−0.793
−0.908
−0.295
1.001
0.130
0.013
0.367
1981222
11489580

isosafrole
20
−0.798
0.369
−0.913
−1.060
0.397
0.462
−1.283
−0.860
−1.917
1984013
11488488

11a-acetoxykhivorin
20
0.824
−0.824
−1.019
−0.178
−0.252
0.082
0.676
0.586
0.662
2060025
11488039

dihydrofissinolide
20
0.139
−0.079
−1.189
0.196
1.029
−0.122
−0.253
−0.350
0.041
2060026
11488155

3beta-hydroxydeoxodihydrogedunin
20
−0.364
0.638
−0.540
0.674
0.170
0.591
−0.585
−0.648
−0.302
2060027
11488157

bussein
20
0.575
−0.071
−1.406
0.367
−0.449
−1.496
1.630
1.431
1.660
2060028
11488042

3beta-acetoxydeoxodihydrogedunin
20
0.311
0.077
−0.528
0.254
0.055
0.759
−1.016
−1.055
−0.694
2060029
11488158

carapin
20
1.424
0.175
−0.925
−0.524
1.897
−0.096
0.512
0.665
0.058
2060030
11488043

cedrelone
20
−4.680
−8.647
−6.617
−3.459
−3.982
−5.998
ND
ND
ND
2060031
11488044

totaralolal
20
0.591
0.829
1.526
0.460
1.617
−0.226
−0.700
−0.401
−1.230
2060034
11488084

deacetylgedunin
20
−0.032
0.232
−0.958
0.349
−0.966
−0.489
−0.322
−0.244
−0.484
2060035
11488045

ptaeroxylin
20
−0.025
−0.704
0.160
0.238
0.259
0.599
−0.853
−0.907
−0.641
2060036
11488099

3alpha-acetoxydihydrodeoxygedunin
20
0.781
−0.586
−1.653
1.157
2.371
0.179
−0.987
−1.123
−0.584
2060037
11488075

deoxyandirobin
20
0.894
1.237
0.232
0.381
−1.077
1.196
1.352
1.240
1.246
2060038
11488048

peucenin
20
−0.906
0.465
−1.695
−0.057
−0.014
0.494
0.148
0.051
0.361
2060039
11488160

2-ethoxycarbonyl-2-hydroxy-5,7-
20
0.511
−1.500
−0.260
0.215
0.774
0.161
0.280
0.232
0.273
2060040
11488031

dimethoxyisoflavanone

griseofulvic acid
20
0.176
−1.279
−0.469
−0.666
−0.323
0.724
−0.370
−0.442
−0.209
2060043
11488028

iriginol hexaaceatate
20
−0.291
0.302
−0.565
−0.204
0.815
−0.315
0.928
0.859
0.938
2060044
11488216

retusoquinone
20
−5.371
−8.276
−6.075
−3.628
−3.565
−5.303
ND
ND
ND
2060045
11488435

epoxy (4,5alpha)-4,5-dihydrosantonin
20
0.133
0.475
0.041
0.199
−1.367
0.552
−0.736
−0.614
−0.901
2060046
11487977

diacetyldideisovaleryl-rhodomyrtoxin
20
−0.779
−0.179
0.875
1.937
0.967
0.057
−0.776
−0.742
−0.703
2060048
11488606

eugenitol
20
−0.575
0.166
−1.139
−0.541
1.256
−0.041
0.471
0.168
0.962
2060049
11488565

isoeugenitol
20
0.377
0.995
−0.500
0.369
1.129
0.662
−0.717
−0.647
−0.680
2060051
11488385

norstictic acid
20
−0.899
2.102
−0.567
0.903
0.560
0.471
0.518
0.774
−0.148
2060054
11489744

dihydrogedunin
20
0.637
0.315
−0.017
1.079
−0.690
0.460
0.575
0.613
0.323
2060055
11488049

heteropeucenin, methyl ether
20
−0.034
−0.142
−1.476
0.886
0.256
0.416
0.299
0.328
0.217
2060056
11488161

fissinolide
20
0.060
0.175
−1.576
−0.324
0.475
−0.167
0.534
0.385
0.777
2060057
11488431

oleanoic acid
20
0.492
1.083
−0.720
−0.910
−0.144
0.754
−1.379
−1.408
−1.014
2060058
11488167

havanensin triacetate
20
1.042
0.189
−0.499
0.898
0.140
−0.315
0.716
0.370
1.210
2060059
11488051

deacetoxy-7-oxogedunin
20
0.089
−0.025
−0.029
1.322
−0.301
0.047
−0.407
−0.287
−0.632
2060060
11488052

dihydrospatheliachromene
20
−0.538
0.342
−1.802
−0.174
1.483
0.068
−0.666
−0.620
−0.569
2060061
11488162

7-deacetoxy-7-oxokhivorin
20
0.053
−0.644
−0.095
0.258
0.070
−0.184
0.777
0.690
0.738
2060062
11488053

khayanthone
20
1.156
0.345
−0.382
0.962
0.015
−0.669
1.491
1.510
1.095
2060063
11488054

khayasin
20
−0.077
0.871
−0.812
0.007
0.528
−0.281
0.671
0.798
0.326
2060064
11488211

oxonitine
20
−1.338
0.116
−1.730
−1.019
−0.167
0.394
−0.636
−0.938
0.147
2060065
11488170

angolensic acid, methyl ester
20
1.019
−0.097
0.322
0.163
0.465
−0.204
0.827
0.729
0.813
2060066
11488055

gedunol
20
0.438
0.637
−1.248
0.897
0.132
0.758
−1.545
−1.561
−1.174
2060067
11488387

sarmentoside B
20
−0.939
0.526
−2.387
−0.760
0.222
0.251
−1.573
−1.615
−1.141
2060068
11488171

irigenin, 7-benzyl ether
20
−0.334
−0.373
−1.179
0.948
1.548
−0.617
−1.362
−1.386
−1.100
2060069
11488016

iretol
20
−0.552
−0.628
−0.086
−0.404
−0.393
0.347
−0.881
−0.583
−1.366
2060070
11488018

haematommic acid, ethyl ester
20
−0.557
−0.324
−0.761
−0.120
0.478
−0.104
0.450
0.387
0.537
2060071
11488445

rotenonic acid
20
0.206
0.763
−0.731
0.050
0.173
0.365
−0.064
−0.010
−0.108
2060078
11488212

dihydrogambogic acid
20
−5.468
−8.298
−6.208
−3.431
−2.239
−5.191
ND
ND
ND
2060079
11488443

tetrahydrogambogic acid
20
1.434
−0.668
−1.090
−1.438
0.460
−0.932
−0.478
−0.409
−0.490
2060080
11489622

2-isoprenyl-3-hydroxy-5-methyl-a-pyrone
20
−1.025
0.004
0.055
−0.641
1.032
−0.568
0.309
0.277
0.271
2060081
11489775

methyl 7-desoxypurpurogallin-7-carboxylate
20
−0.836
0.028
−2.317
−0.254
0.800
−0.229
0.231
0.287
0.117
2060082
11488271

trimethyl ether

6-hydroxyangolensic acid methyl ester
20
1.224
−0.193
−0.490
0.463
−0.249
0.817
−1.426
−1.425
−1.206
2060083
11488057

obacunol
20
2.016
1.116
−0.982
0.464
−0.134
0.859
−0.906
−0.927
−0.734
2060085
11488058

entandrophragmin
20
0.672
1.006
−0.737
0.113
1.351
−0.703
0.467
0.149
1.061
2060086
11488156

swietenine
20
1.223
0.027
−0.653
−0.241
−0.259
0.244
−1.282
−1.274
−1.090
2060087
11488060

fraxidin methyl ether
20
−1.325
0.407
−2.013
−0.713
0.276
−0.098
−0.124
−0.104
−0.103
2060088
11488173

utilin
20
1.131
1.189
−1.571
−0.122
0.482
−0.038
−0.939
−0.861
−0.975
2060089
11488062

humilin A
20
0.840
−0.106
−1.117
0.314
−0.028
0.423
−0.789
−0.820
−0.623
2060090
11488061

niloticin
20
1.304
0.356
−0.481
0.461
0.817
0.136
0.543
0.648
0.151
2060091
11488063

3-acetoxypregn-16-en-12,20-dione
20
−0.873
1.152
−0.553
−0.216
0.201
−0.050
−0.885
−0.775
−0.958
2060092
11488576

odoratone
20
0.542
0.474
−1.060
0.367
0.083
0.707
−0.994
−0.988
−0.873
2060093
11488064

swietenolide-3-acetate
20
−0.503
1.431
−0.776
1.006
0.237
0.668
−1.057
−1.093
−0.838
2060094
11488065

1,7-dideacetoxy-1,7-dioxokhivorin
20
0.042
0.712
−0.142
−0.535
0.352
0.539
−0.558
−0.585
−0.355
2060096
11488178

3beta-chloroandrostanone
20
−0.424
1.376
−1.203
−0.860
−0.077
1.021
−1.190
−1.192
−0.907
2060098
11488179

7-deshydroxypyrogallin-4-carboxylic acid
20
0.121
0.330
−0.460
−1.109
−0.210
0.419
−0.997
−1.039
−0.770
2060100
11487990

8-iodocatechin tetramethyl ether
20
0.377
0.343
−1.359
0.146
−0.448
0.237
−1.194
−0.985
−1.411
2060101
11488697

tetramethylhaematoxylone
20
0.837
−0.771
−0.703
−0.921
−0.215
−0.056
−0.273
−0.365
−0.093
2060102
11488005

rotenonic acid, methyl ether
20
0.582
−4.969
−3.898
−3.751
−3.513
−3.644
−2.268
−1.024
−4.305
2060103
11488941

methylnorlichexanthone
20
−0.496
0.429
−1.082
0.258
0.477
0.385
−0.661
−0.566
−0.698
2060104
11489618

irigenin trimethyl ether
20
−0.060
0.108
−0.808
−0.174
−0.074
0.129
−0.792
−0.790
−0.699
2060106
11488007

3,4-dimethoxydalbergione
20
−4.588
−5.364
−6.200
−3.787
−1.269
−5.551
−3.047
−2.944
−2.724
2060107
11488120

2′-methoxyformonetin
20
0.477
1.998
−1.138
0.388
1.137
−1.318
−0.484
−0.561
−0.296
2060110
11488004

cearoin
20
−1.078
−1.727
−2.331
−1.006
−2.274
−1.478
−1.672
−1.568
−1.603
2060111
11489770

resveratrol 4′-methyl ether
20
−0.225
−0.649
−1.056
−0.389
0.225
0.142
−0.005
−0.063
0.065
2060112
11487862

orsellinic acid
20
−0.320
−1.140
−1.311
−0.846
1.236
−0.015
−0.348
−0.350
−0.333
2060113
11488121

cotarnine
20
−0.398
1.285
−0.587
−1.103
−0.007
0.068
0.049
0.159
−0.151
2060114
11488180

prenyletin
20
0.919
0.659
−1.166
0.772
−0.090
0.150
0.113
−0.015
0.282
2060115
11488066

khayasin C
20
−1.021
−0.324
−1.678
−0.095
−0.078
−0.654
0.442
0.033
1.232
2060116
11488205

13-methyl-4,4-bisnor-8,11,13-podocarpatrien-
20
−0.093
−0.267
−2.132
−0.470
0.072
0.009
0.903
0.870
0.748
2060117
11488101

3-one

3alpha-hydroxy-3-deoxyangolensic acid methyl
20
0.949
0.398
−1.268
−0.043
0.799
−0.141
−0.456
−0.474
−0.377
2060118
11488071

ester

3-chloro-8beta-hydroxycarapin, 3,8-hemiacetal
20
0.170
0.067
−1.971
−0.678
2.012
0.075
−1.044
−0.883
−1.228
2060121
11488072

xanthyletin
20
−0.674
0.349
−1.741
−0.220
0.217
−0.029
1.029
0.924
1.085
2060122
11488181

totarol-19-carboxylic acid, methyl ester
20
−0.739
2.434
1.019
−0.409
1.290
0.085
−0.323
−0.005
−0.853
2060124
11488182

19-hydroxytotarol
20
−0.207
0.803
1.198
0.453
1.558
1.305
−0.041
−0.128
0.086
2060126
11488085

16-deoxomexicanolide 16-methyl ether
20
0.470
−0.197
−2.098
−0.162
0.240
−0.339
−0.225
−0.320
−0.037
2060127
11488070

chukrasin methyl ether
20
−0.822
0.533
−0.818
−1.084
0.777
−0.248
0.352
0.417
0.198
2060128
11488183

khivorin
20
0.807
−0.294
−1.421
−0.145
0.187
0.229
−0.144
−0.022
−0.423
2060129
11488078

(R)-angolensin
20
−0.164
1.320
−0.743
−0.444
0.225
−0.063
0.403
0.703
−0.245
2060130
11488210

2-ethoxycarbonyl-5,7-dihydroxy-8,3′,4′,5′-
20
−1.124
0.782
−0.761
−0.397
0.244
−0.783
−1.306
−1.229
−1.218
2060131
11488664

tetramethoxyisoflavone

solidagenone
20
−0.409
0.314
0.084
−0.242
1.734
−0.061
0.127
−0.023
0.441
2060132
11489574

iridin
20
−0.441
0.161
−1.958
0.076
0.927
−0.474
−0.755
−0.602
−0.990
2060133
11488014

sphondin
20
−0.790
0.064
−0.661
0.136
1.692
0.091
−0.684
−0.605
−0.666
2060134
11489575

euparin
20
0.021
−1.071
−0.912
−0.010
0.795
0.419
1.120
1.293
0.484
2060136
11488122

isotectorigenin trimethyl ether
20
0.976
−0.305
−1.465
0.413
0.359
0.640
0.437
0.426
0.418
2060137
11488394

gibberellic acid
11.54
−0.171
1.388
−0.432
2.622
0.246
0.714
0.021
0.066
−0.090
2060138
11468113

gibberellic acid
20
−0.081
0.413
0.661
−0.439
0.512
0.031
−0.014
0.077
−0.264
2060138
11488127

duartin, dimethyl ether
20
1.330
0.049
−0.975
0.556
0.796
−0.531
−1.156
−1.362
−0.571
2060139
11487996

isobergaptene
20
0.375
−0.303
−1.025
−0.112
1.329
0.486
0.514
0.338
0.715
2060140
11488129

4,4′-dimethoxydalbergione
20
−0.207
−0.089
−2.648
−0.993
−0.802
−1.432
−0.842
−0.677
−0.975
2060141
11488413

crassin acetate
20
−2.757
0.769
−1.220
0.374
−1.394
−1.840
−0.720
−0.685
−0.703
2060142
11488130

4-methoxy-4′-hydroxy-dalbergione
20
1.548
1.255
−0.877
0.406
0.639
0.803
−1.401
−1.406
−1.071
2060143
11488378

6,3′-dimethoxyflavone
20
0.413
−2.332
−1.534
1.915
−0.882
0.245
0.072
0.087
−0.021
2060144
11487847

7-deacetoxy-7-oxodeoxygedunin
20
0.224
0.609
−1.467
0.757
−0.489
0.166
−1.791
−1.586
−1.925
2060145
11488069

12-hydroxy-4,4-bisnor-4,8,11,13-
20
−0.592
0.589
−0.984
−0.484
0.676
−0.516
0.075
−0.281
0.846
2060146
11488184

podocarpatetraen-3-one

7-deacetylkhivorin
20
0.893
1.348
0.608
−0.049
−0.618
0.079
0.477
0.543
0.188
2060147
11488047

chrysarobin
20
−0.685
0.593
−1.646
−0.726
0.805
−0.074
−1.153
−1.387
−0.401
2060149
11488408

deoxyandirobin lactone
20
0.281
0.967
−1.509
−0.395
0.837
0.893
−1.510
−1.558
−1.179
2060150
11488073

7beta-hydroxy-7-desacetoxykhivorinic acid,
20
−0.160
0.505
−0.485
−0.940
0.252
−0.283
0.553
0.426
0.736
2060151
11488257

methyl ester

isogedunin
20
0.404
−0.722
−1.716
−0.489
1.276
0.050
0.805
0.883
0.523
2060152
11489711

14-methoxy-4,4-bisnor-4,8,11,13-
20
−0.577
−0.516
−1.530
−0.506
0.673
−0.293
−0.465
−0.372
−0.626
2060153
11488103

podocarpatetraen-3-one

3-deoxo-3beta-acetoxydeoxydihydrogedunin
20
1.066
−0.605
−1.633
1.215
1.249
0.398
−0.742
−0.791
−0.559
2060154
11488074

desacetyl (7)khivorinic acid, methyl ester
20
0.474
0.731
−0.427
−0.579
0.177
1.004
−0.376
−0.485
−0.039
2060155
11488197

prieurianin
20
−0.894
2.125
−1.263
1.108
−1.358
−1.620
2.020
1.896
1.931
2060156
11488296

dihydroxy (3alpha,12alpha)pregnan-20-one
20
−0.622
−0.294
−1.160
−0.540
0.206
−0.685
−0.928
−0.972
−0.621
2060157
11488185

deoxygedunol acetate
20
−0.767
0.032
−1.930
0.137
1.251
0.095
−0.815
−0.850
−0.639
2060158
11488102

dihydrogedunic acid, methyl ester
20
0.103
0.122
−1.062
−0.320
0.411
−0.443
0.244
0.141
0.438
2060159
11488186

deoxodeoxydihydrogedunin
20
0.876
0.419
−0.551
0.941
0.995
0.837
−1.452
−1.370
−1.397
2060160
11488077

obliquin
20
0.539
1.040
−0.268
0.088
0.977
−1.172
−0.313
−0.459
0.105
2060161
11488164

3-deoxo-3beta-hydroxymexicanolide 16-enol
20
0.290
−0.075
−1.922
−0.059
1.279
−0.040
−0.203
−0.247
−0.133
2060162
11488080

ether

mundoserone
20
−0.425
−1.275
−1.681
0.837
−0.608
0.418
−0.606
−0.643
−0.452
2060163
11487999

dehydrodihydrorotenone
20
−0.172
0.084
−3.034
0.125
0.051
−0.211
−0.001
−0.290
0.535
2060165
11488000

5-hydroxyiminoisocaryophyllene
20
0.181
0.874
1.325
0.413
0.922
0.117
−0.023
−0.273
0.421
2060166
11488136

methyl 7-deshydroxypyrogallin-4-carboxylate
20
−0.873
1.034
−1.261
−1.695
0.145
0.133
−1.502
−1.394
−1.395
2060167
11488418

abienol
20
−0.199
1.677
0.338
0.334
2.467
0.211
0.498
0.091
1.214
2060168
11488614

2′,2′-bisepigallocatechin digallate
20
0.851
0.573
−0.826
−1.132
−0.130
0.616
−0.865
−0.836
−0.808
2060169
11487982

senecrassidiol 6-acetate
20
0.328
−0.482
0.557
−0.041
1.016
0.477
1.420
1.414
1.085
2060170
11488132

bromo-3-hydroxy-4-(succin-2-yl)-caryolane
20
−0.498
−0.346
−0.892
−0.084
0.604
0.551
−1.029
−0.612
−1.624
2060172
11489717

gamma-lactone

cadin-4-en-10-ol
20
−0.101
0.543
−0.041
−0.297
0.180
0.328
−0.610
−0.244
−1.252
2060173
11488477

sericetin
20
−0.783
−1.140
−1.507
6.788
0.124
−0.335
−0.890
−0.670
−1.132
2060174
11489713

epi(13)torulosol
20
0.367
1.007
0.603
0.022
1.180
0.483
0.491
0.342
0.643
2060175
11488135

8-hydroxy-15,16-bisnor-11-labden-13-one
20
−1.702
0.871
−0.248
0.798
0.504
0.550
−0.554
−0.078
−1.430
2060176
11488457

1,2alpha-epoxydeacetoxydihydrogedunin
20
0.074
−0.934
−2.000
0.210
3.350
−0.224
−0.921
−1.080
−0.468
2060177
11488081

sarmentogenin
20
0.694
1.794
−0.191
−0.354
−0.151
0.614
0.508
0.691
0.077
2060178
11488208

14-methoxy-4,4-bisnor-8,11,13-podocarpatrien-
20
−0.060
2.441
−1.068
1.124
−0.109
1.307
−0.872
−0.900
−0.612
2060179
11488219

3-one

dihydroptaeroxylin
20
0.605
0.530
−0.526
−0.192
0.151
0.403
−0.581
−0.410
−0.787
2060184
11488187

homopterocarpin
20
0.549
0.381
−0.578
−0.306
−0.616
0.575
−0.918
−0.713
−1.126
2060185
11488188

strophanthidinic acid
20
−0.745
0.463
−1.651
−0.875
−0.059
0.166
−0.553
−0.400
−0.726
2060186
11488189

2-isopropyl-3-methoxycinnamic acid
20
0.040
−1.528
−2.002
−0.155
0.433
0.274
0.153
0.153
0.071
2060187
11488100

hydroxy (3beta)isoallospirost-9 (11)-ene
20
0.035
−0.703
−1.944
−0.423
0.244
−0.048
−0.457
−0.619
−0.081
2060188
11488091

11-ketorockogenin acetate
20
−0.031
0.241
−0.700
−0.584
0.933
−0.702
−1.105
−1.026
−0.969
2060190
11488985

2-methylene-5-(2,5-dioxotetrahydrofuran-3-yl)-
20
−0.749
−0.614
−0.968
−0.249
0.012
0.345
−1.109
−1.009
−1.046
2060191
11489720

6-oxo-10,10-dimethylbicyclo[7:2:0]undecane

beta-caryophyllene alcohol
20
−0.960
−0.243
−1.859
−0.433
1.180
−1.030
0.155
0.105
0.264
2060192
11489543

3-amino-beta-pinene
20
−0.108
0.438
−0.906
−0.519
0.421
0.460
−1.376
−1.341
−1.138
2060193
11489719

everninic acid
20
−0.592
0.947
−1.123
−0.942
0.423
0.115
1.491
1.517
1.116
2060194
11488501

3-nor-3-oxopanasinsan-6-ol
20
0.209
0.158
−0.492
−0.006
0.172
0.864
−0.605
−0.831
0.004
2060195
11489587

beta-toxicarol
20
0.672
−2.000
−1.498
0.899
−0.188
−0.239
−1.508
−1.773
−0.627
2060196
11488395

2-methoxy-5 (6)epoxy-tetrahydrocaryophyllene
20
−1.011
0.358
−0.794
−0.699
0.120
0.933
−0.497
−0.466
−0.439
2060197
11489588

12a-hydroxy-5-deoxydehydromunduserone
20
−0.940
−0.089
−1.976
−0.179
0.823
−0.179
0.211
0.193
0.239
2060198
11489533

3,7-epoxycaryophyllan-6-ol
20
−0.644
−0.499
−1.302
−0.461
0.255
0.604
−1.018
−1.203
−0.407
2060199
11489590

2-hydroxy-5 (6)epoxy-tetrahydrocaryophyllene
20
−0.772
−0.149
−0.836
−0.739
0.074
0.236
−0.347
−0.447
−0.043
2060200
11489591

avocadyne
20
0.816
−0.151
−0.369
−0.266
0.322
0.738
0.405
0.457
0.242
2060201
11489537

3,7-epoxycaryophyllan-6-one
20
0.433
−0.022
−0.698
−1.003
0.603
0.131
−0.812
−0.824
−0.595
2060202
11489592

methylorsellinic acid, ethyl ester
20
0.459
0.341
−0.661
−0.478
−0.293
0.754
−0.990
−1.040
−0.770
2060203
11487989

clovanediol diacetate
20
−0.119
−0.009
−0.708
−0.599
−0.318
0.384
−0.020
0.007
−0.026
2060204
11489593

sitosteryl acetate
20
−0.827
0.613
−0.775
−0.192
0.930
−0.443
−0.233
−0.389
0.180
2060206
11488195

1,3-dideacetyl-7-deacetoxy-7-oxokhivorin
20
0.190
−0.006
−1.399
1.329
1.267
0.226
−0.665
−0.716
−0.497
2060207
11488096

3,16-dideoxymexicanolide-3beta-diol
20
−0.384
−0.547
−1.091
0.154
0.587
−0.130
0.150
0.282
−0.202
2060208
11488022

12a-hydroxy-9-demethylmunduserone-8-
20
0.509
1.728
−0.976
−0.494
−0.738
0.670
−0.404
−0.162
−0.773
2060209
11488209

carboxylic acid

1,7-dideacetoxy-1,7-dioxo-3-deacetylkhivorin
20
−0.023
−0.155
−1.103
−0.335
0.122
0.113
−0.911
−0.866
−0.875
2060212
11488097

epoxy (1,2alpha)-7-deacetoxy-7-oxo-
20
−0.363
1.049
−0.154
0.419
−0.893
0.935
−1.505
−1.598
−0.990
2060213
11488147

deoxydihydrogedunin

mundulone
20
−1.113
−4.544
−2.487
3.037
−0.141
−0.843
−1.719
−1.888
−1.091
2060214
11488105

7-desacetoxy-6,7-dehydrogedunin
20
−0.973
2.695
−1.891
−1.799
−3.492
0.198
−1.430
−0.695
−2.631
2060215
11488277

isorotenone
20
−1.954
−5.273
−4.373
−1.329
−0.782
−3.397
−3.751
−3.017
−4.571
2060216
11488025

dihydromundulone
20
0.816
−0.792
0.189
−0.530
0.537
−0.210
0.414
0.513
0.168
2060217
11489716

dihydromunduletone
20
1.580
−2.030
−0.805
2.250
−0.049
−0.146
−1.331
−1.276
−1.248
2060218
11487985

caryophyllenyl acetate
20
−0.394
−0.165
−1.220
−0.241
0.228
0.671
0.235
0.117
0.457
2060219
11489594

3-pinanone oxime
20
−0.344
0.209
−0.210
−0.415
−0.152
0.014
0.141
0.031
0.386
2060220
11489576

epiafzelechin trimethyl ether
20
0.557
0.312
−0.884
−0.324
−0.190
1.099
0.019
−0.134
0.350
2060221
11489582

15-norcaryophyllen-3-one
20
0.557
0.833
−1.582
0.034
−0.667
0.656
−0.016
−0.076
0.137
2060222
11489577

catechin tetramethylether
20
0.435
0.310
−0.573
−0.172
−0.094
0.586
−1.052
−1.106
−0.798
2060223
11487980

epicatechin
20
0.687
0.544
−1.556
−1.802
−0.199
0.850
−0.754
−0.773
−0.631
2060224
11487981

theaflavin monogallate
20
0.945
0.164
−0.786
−0.581
−0.820
1.252
−0.211
−0.017
−0.612
2060226
11487978

xylocarpus A
20
1.708
2.503
−0.074
0.427
1.026
0.822
−0.008
0.110
−0.206
2060228
11488207

epigallocatechin 3,5-digallate
20
0.969
1.156
−1.667
−2.135
0.118
1.040
−1.581
−1.625
−1.133
2060229
11488393

3-deacetylkhivorin
20
0.398
−0.078
−0.317
0.274
0.619
−0.600
−0.661
−0.823
−0.272
2060230
11488046

dihydrodeoxygedunin
20
−0.004
1.697
−0.637
0.443
1.030
0.751
−1.009
−1.073
−0.631
2060232
11488149

3,16-dideoxymexicanolide-3alpha-diol
20
−0.318
1.308
−1.094
−0.206
0.758
0.491
−1.044
−1.053
−0.771
2060233
11488150

gangaleoidin
20
0.889
−1.768
−1.213
−1.233
1.356
−0.876
−0.512
−0.587
−0.310
2060234
11488110

1 (2)alpha-epoxydeoxydihydrogedunin
20
0.015
0.869
−1.048
0.074
2.784
0.022
−0.801
−0.831
−0.539
2060235
11488151

deacetoxy(7)-7-oxokhivorinic acid
20
−0.174
0.363
−1.282
−0.539
2.352
0.816
−0.919
−0.937
−0.664
2060237
11488152

gyrophoric acid
20
−0.579
0.125
−0.977
−0.842
0.897
−0.557
−0.471
−0.546
−0.289
2060238
11488024

merogedunin
20
−0.222
2.064
−0.645
−0.214
0.741
0.490
−0.254
−0.160
−0.350
2060240
11488153

dihydro-7-desacetyldeoxygedunin
20
−0.527
1.060
−1.403
−0.170
0.608
0.599
−0.961
−0.719
−1.218
2060241
11488154

pectolinarin
20
−0.100
−0.465
−0.475
−0.280
1.058
−0.739
−1.381
−1.292
−1.349
2060242
11488026

tetrahydrotrimethylhispidin
20
−1.602
0.150
−0.667
−0.432
0.719
−0.281
−0.448
−0.322
−0.649
2060244
11489774

melezitose
20
−0.843
0.268
−0.968
−0.605
−0.125
0.284
−0.502
0.054
−1.553
2060245
11488468

andrographolide
20
−0.686
0.416
−0.901
−0.165
−1.813
−0.044
−1.323
−0.698
−2.361
2060246
11488518

7-hydroxy-8,4′-dimethoxyisoflavone
20
−1.022
0.309
−1.073
−0.417
1.404
0.363
−0.962
−0.994
−0.667
2060249
11489570

kynuramine
20
0.319
2.131
−1.264
−0.127
1.180
1.161
0.070
0.093
0.045
2060251
11488383

kynurenine
20
−0.110
0.528
−0.912
−0.058
1.941
0.162
−0.039
−0.088
0.069
2060253
11489196

pelletierine
20
−0.418
1.086
−0.341
−0.120
−0.071
0.349
0.036
0.077
−0.077
2060254
11488467

triacetylresveratrol
20
−0.198
−1.727
−2.002
−3.502
−1.361
0.683
−1.841
−1.858
−1.401
2060255
11489448

chrysanthemyl alcohol
20
0.604
0.964
−0.004
−0.734
0.345
0.264
0.456
0.495
0.331
2060256
11489584

catechin pentaacetate
20
0.652
1.098
−1.126
−2.799
−1.649
0.425
0.269
0.314
0.161
2060258
11489583

anhydrobrazilic acid
20
−0.072
−1.204
−1.007
−0.353
0.388
0.579
1.730
1.559
1.678
2060259
11488012

liquiritigenin
20
1.353
−0.998
−0.429
1.004
0.301
0.523
−0.749
−0.547
−1.069
2060260
11487857

4,7-dimethoxyflavone
20
−0.067
−0.035
−0.472
−0.795
1.067
0.031
1.306
1.526
0.539
2060260
11487873

zeorin
20
0.495
−0.326
−0.387
−0.941
0.166
0.088
0.381
0.278
0.571
2060261
11489643

2,3,4′-trihydroxy-4-methoxybenzophenone
20
−0.403
−0.035
−0.475
−1.356
−0.472
0.378
−1.557
−1.472
−1.476
2060263
11488020

dehydro (11,12)ursolic acid lactone
20
−0.003
0.599
0.402
−0.429
0.385
−0.175
0.058
0.104
−0.002
2060264
11489595

cholic acid, methyl ester
20
−0.383
2.202
−1.021
0.065
0.295
0.018
−0.751
−0.852
−0.394
2060265
11489189

11-oxoursolic acid acetate
20
1.094
−1.477
−1.214
−0.524
0.280
−1.393
−0.240
−0.304
−0.027
2060266
11489596

lithocholic acid
20
−0.094
−0.617
−1.586
−0.522
0.854
0.035
−0.631
−0.596
−0.579
2060267
11489190

3-oxoursan (28-13)olide
20
0.638
0.062
−1.871
−0.332
1.010
0.991
−1.322
−1.228
−1.205
2060268
11489597

dehydroabietamide
20
0.807
0.588
−0.187
1.642
−0.130
0.030
−0.843
−0.731
−0.877
2060270
11489598

rhodomyrtoxin B
20
−1.003
−3.678
0.193
4.272
−3.198
−1.949
−1.271
−0.783
−1.960
2060271
11489467

dihydrocaryophyllen-5-one
20
0.219
0.364
−1.453
0.090
0.483
0.620
−0.496
−0.513
−0.317
2060272
11489599

muurolladie-3-one
20
−0.720
−0.436
−1.161
0.063
−0.490
−0.234
−0.747
−0.745
−0.569
2060274
11489600

ginkgolide A
20
0.380
−0.205
−1.019
−0.271
1.848
0.541
−0.247
−0.286
−0.123
2060276
11489194

3,8-dimethoxyflavone
20
0.930
0.242
−0.252
−0.103
1.553
0.361
0.399
0.315
0.492
2060277
11489174

oleananoic acid
20
−0.265
−0.334
−1.750
−0.645
0.809
0.172
−0.839
−0.751
−0.815
2060279
11489539

neotigogenin acetate
20
−0.705
−0.797
−1.611
−0.822
−0.437
−0.049
−0.890
−0.925
−0.693
2060280
11488088

dihydrocelastrol
20
−4.120
−2.447
−5.524
−3.514
−3.065
−4.583
−0.295
2.183
−5.217
2060287
11488929

chrysanthellin A
20
−4.075
−2.958
−4.661
−1.860
−1.565
−4.088
−0.126
−0.394
0.474
2060290
11489451

3alpha-hydroxydeoxodihydrogedunin
20
0.065
0.835
−1.072
−0.061
1.207
1.091
−0.892
−0.832
−0.857
2060291
11488588

tridesacetoxykhivorin
20
−0.863
1.505
−1.476
0.059
0.504
−0.452
−0.649
−0.627
−0.515
2060292
11488174

cedryl acetate
20
−0.311
0.493
−0.176
−0.042
1.566
0.388
0.067
0.184
−0.149
2060293
11489728

deoxysappanone B 7,3′-dimethyl ether
20
−1.120
−1.027
−2.870
−0.637
−1.712
−0.951
2.118
2.250
1.383
2060294
11488013

dihydro-obliquin
20
−0.141
−0.036
−0.661
−0.159
1.045
−0.662
0.233
0.192
0.303
2060295
11488166

dihydrojasmonic acid
20
−1.223
0.502
−0.149
−0.294
0.827
−0.847
−0.313
−0.168
−0.505
2060298
11489466

punctaporin B
20
0.554
−0.771
−0.596
−0.174
0.731
0.175
−0.242
−0.049
−0.555
2060299
11489638

isoginkgetin
20
2.182
−0.550
−1.024
−4.387
1.106
−0.400
−0.589
−0.318
−1.087
2060300
11488118

diosmetin
20
0.174
−0.756
−1.922
−2.701
−0.014
−0.666
−0.892
−1.158
−0.134
2060301
11489454

phytol
20
−0.520
−0.426
−0.544
−0.233
0.940
0.020
−0.177
−0.098
−0.270
2060302
11489725

2-methyl-3-hydroxyethylenepyran-4-one
20
0.309
−0.367
−0.725
−0.608
0.234
−0.244
−0.128
−0.012
−0.305
2060303
11489462

cellobiose (D[+])
20
0.390
1.049
0.411
−0.571
−0.298
0.380
−0.127
0.051
−0.466
2060304
11489318

nonic acid
20
−1.043
0.366
−1.857
−0.931
1.211
−0.133
−0.080
−0.104
0.061
2060305
11488911

rhodinyl acetate
20
−0.197
0.959
−0.833
−0.631
−0.024
0.137
0.378
0.774
−0.504
2060306
11488508

3-deshydroxysappanol trimethyl ether
20
0.416
−0.268
−0.416
0.033
1.385
−0.948
0.465
0.557
0.224
2060307
11489446

abscisic acid
20
0.309
0.509
−1.053
−0.565
−0.476
0.179
0.469
0.509
0.299
2060308
11489319

strophanthidin
20
−1.016
0.044
−1.573
−0.481
1.036
0.687
−0.789
−0.525
−1.094
2060309
11489070

chol-11-enic acid
20
−0.456
−0.496
−1.164
−0.652
0.737
0.383
−0.069
−0.195
0.246
2060311
11488441

humulene
20
−0.070
0.403
−1.208
−0.232
0.679
−0.100
−0.096
−0.188
0.060
2060313
11489811

leoidin dimethyl ether
20
0.677
0.448
−0.726
−0.320
−0.121
1.032
−1.008
−0.595
−1.691
2060314
11488637

methyl robustone
20
0.848
−0.638
−0.344
0.715
−0.347
0.373
0.033
0.075
−0.063
2060316
11488642

derrusnin
20
1.067
0.050
−1.630
0.025
4.060
0.511
0.039
−0.129
0.417
2060317
11488231

antheraxanthin
20
−0.496
0.403
−0.804
−0.305
0.244
−0.206
0.013
0.026
−0.011
2060318
11489395

5beta-12-methoxy-4,4-bisnor-8,11,13-
20
−0.071
0.458
−2.008
−0.173
1.860
0.380
−0.632
−0.582
−0.652
2060320
11488082

podocarpatrien-3-one

rhoifolin
20
0.089
0.053
−0.683
−0.213
0.471
0.515
−0.838
−0.774
−0.768
2060321
11489457

3,7-dimethoxyflavone
20
−0.730
1.027
−1.089
0.817
0.652
0.982
−0.945
−1.084
−0.434
2060322
11488143

5,2′-dimethoxyflavone
20
−0.228
1.331
−0.219
1.002
0.645
1.046
−0.862
−0.881
−0.607
2060323
11488139

carylophyllene oxide
20
−0.547
0.604
−0.713
−0.246
0.636
0.321
−0.087
0.060
−0.324
2060324
11488450

isocorydine
11.72
−1.678
−0.052
−1.041
−1.052
1.214
0.632
0.084
0.451
−0.664
2060325
11467745

isocorydine
20
1.230
0.593
−1.215
−0.017
−0.096
0.355
−0.462
−0.463
−0.322
2060325
11488382

bebeerine
20
−0.728
0.034
−1.681
−0.800
0.759
0.389
−0.005
−0.028
0.119
2060327
11489053

rhodomyrtoxin
20
−0.636
−2.765
2.413
2.834
0.397
−1.200
0.357
0.412
0.206
2060328
11489445

glucitol-4-gucopyanoside
20
−0.508
−0.172
−0.795
−0.454
0.351
0.305
−1.143
−1.087
−1.006
2060330
11489429

caryophyllene
20
−0.255
1.810
−0.525
1.045
0.996
−0.121
0.119
0.216
−0.100
2060331
11489186

coniferyl alcohol
20
−0.771
0.124
−1.094
−0.719
−0.450
0.296
−0.593
−0.688
−0.251
2060332
11489430

piceid
20
−0.341
1.229
−0.826
0.088
0.862
0.272
0.110
0.088
0.124
2060333
11489184

loganic acid
20
1.214
−0.276
−0.538
−0.193
−0.346
−0.485
−0.463
−0.274
−0.800
2060334
11489787

maackiain
20
−1.052
1.146
−0.578
0.391
0.879
0.969
−0.561
−0.285
−1.049
2060335
11489741

3,4-didesmethyl-5-deshydroxy-3′-
20
−1.198
0.234
−1.279
−1.362
0.189
0.255
1.215
1.496
0.371
2060336
11489773

ethoxyscleroin

centaurein
20
−0.006
−0.337
−1.640
−0.744
−0.090
−0.039
0.497
0.388
0.657
2060337
11489433

triptophenolide
20
−0.599
−2.142
−1.067
1.886
−1.072
−0.593
−0.110
0.038
−0.350
2060338
11489434

brucine
20
1.605
0.579
−1.270
0.552
0.930
0.660
−1.106
−1.084
−0.887
2060339
11488380

3-benzylidenyl-levulinic acid
20
−0.431
0.543
−0.665
−0.170
0.382
−0.165
−0.639
−0.553
−0.647
2060340
11489435

dihydrorobinetin
20
−1.070
0.456
−1.259
−3.396
−0.393
0.082
−1.192
−1.089
−1.124
2060342
11489459

2-propyl-3-hydroxyethylenepyran-4-one
20
0.162
0.499
−0.906
−0.741
0.195
−0.100
0.682
0.870
0.202
2060343
11489461

hederacoside C
20
−0.672
0.362
−1.226
−0.559
0.079
0.471
−0.809
−0.645
−0.952
2060345
11489439

dihydrocelastryl diacetate
20
−4.472
−4.966
−4.098
−3.309
−3.182
−5.617
−1.199
0.241
−3.815
2060346
11488982

byssochlamic acid
20
−0.241
−1.035
−0.488
−0.092
0.253
−1.053
−0.230
−0.069
−0.458
2060349
11489645

3-alpha-hydroxydeoxygedinin
20
0.156
0.418
−0.319
1.760
0.531
−0.321
−1.171
−1.202
−0.939
2060350
11488076

3beta-acetoxy-23-bromo-isoallospirost-9 (11)-
20
0.710
−0.670
−2.231
−0.260
1.188
0.565
−0.560
−0.585
−0.446
2060351
11488090

ene-12-one

catechin pentabenzoate
20
−1.434
0.169
−1.672
−1.326
0.599
1.272
−0.898
−0.815
−0.896
2060352
11488599

genistein, 8-methyl
20
−0.071
0.160
−1.035
−0.404
1.016
0.189
0.247
0.353
0.023
2060353
11489573

biochanin A
20
0.987
0.278
−0.325
0.033
0.623
−0.416
−0.324
−0.459
−0.042
2060354
11487866

bilirubin
20
−0.649
0.936
−1.287
−1.837
0.249
1.004
0.312
0.250
0.427
2060355
11488451

2,3-dihydroisogedunin
20
0.804
0.069
−1.287
0.221
0.780
0.184
−0.471
−0.444
−0.449
2060357
11488563

lagochilin
20
0.043
−0.029
−0.238
0.277
0.962
−0.862
0.002
−0.036
0.128
2060358
11489444

robustic acid
20
−1.213
0.257
−1.831
−1.086
−0.119
−0.459
−0.930
−0.973
−0.587
2060359
11488981

myosmine
27.36
−0.497
2.062
−1.423
0.326
1.543
1.184
0.445
0.712
−0.195
2060360
11467795

beta-escin
20
−5.049
−5.858
−5.088
−3.416
−3.107
−5.117
−0.914
−0.883
−0.745
2060361
11488351

robustic acid methyl ether
20
0.497
−0.589
0.474
0.692
1.431
0.679
0.230
0.444
−0.223
2060362
11489617

deoxykhivorin
20
0.803
−0.330
−0.494
0.449
−0.038
0.073
−1.026
−0.917
−1.101
2060364
11488067

epoxygedunin
20
0.052
0.227
−1.657
0.274
0.409
0.248
−1.146
−1.130
−1.005
2060365
11488079

deacetoxy-7-oxisogedunin
20
−0.301
−0.566
−0.791
0.332
0.898
0.153
0.816
0.821
0.694
2060366
11488434

erysolin
20
−4.103
−3.023
−3.551
−0.785
−2.871
−1.868
−0.913
−0.850
−0.862
2060367
11489259

abrine
20
0.206
0.140
−1.203
−0.332
1.698
−0.094
0.459
0.430
0.383
2060368
11489812

ichthynone
20
0.234
−0.541
−0.681
−0.325
1.842
0.001
−0.217
−0.088
−0.466
2060370
11488574

8beta-hydroxycarapin, 3,8-hemiacetal
20
0.561
−0.147
0.204
−0.251
1.075
0.436
0.600
0.472
0.789
2060371
11488455

carapin-8 (9)-ene
20
1.357
0.562
−1.272
−0.223
0.766
0.412
0.121
−0.003
0.284
2060372
11488068

kuhlmannin
20
0.333
1.119
−0.487
0.133
0.443
−0.170
0.624
0.646
0.408
2060373
11489808

heudelottin C
20
−0.829
0.840
−0.393
0.373
0.576
0.156
−0.524
−0.245
−1.006
2060374
11488460

diacerin
20
−0.692
0.672
−0.608
0.195
0.228
0.389
−0.446
−0.509
−0.239
2060376
11488639

dihydro-beta-tubaic acid
20
−1.343
−0.543
−0.948
−0.653
0.493
−0.659
−0.303
−0.190
−0.392
2060377
11488984

2,3-dihydroxy-6,7-dichloroquinoxaline
20
−0.077
0.984
−1.458
−1.689
0.085
0.279
−0.724
−0.712
−0.565
2060378
11488353

retusin dimethyl ether
20
0.317
0.241
−1.263
0.378
0.069
−0.199
−0.135
−0.033
−0.331
2060379
11488631

betamethasone
20
−0.984
0.559
−1.063
0.849
0.541
0.130
0.740
0.633
0.853
2060380
11488222

epoxy (1,11)humulene
20
1.157
0.320
−0.802
−0.509
−0.355
0.979
−1.172
−1.115
−1.021
2060382
11489579

deltaline
20
−0.735
0.619
−1.231
−0.496
1.654
0.271
−0.220
−0.062
−0.422
2060386
11488933

3beta,7beta-
20
−0.292
−0.198
−0.810
−0.208
1.848
0.161
−1.124
−1.228
−0.653
2060390
11488191

diacetoxydeoxodeacetoxydeoxydihydrogedunin

2,3,4-trihydroxy-4′-ethoxybenzophenone
20
−0.413
1.562
−2.368
−1.185
0.052
0.440
−0.823
−0.896
−0.478
2060392
11488240

2′,4′-dihydroxychalcone 4′-glucoside
20
0.556
0.137
−1.358
−0.532
1.144
−0.225
−0.189
−0.247
0.004
2060396
11488258

sappanone A dimethyl ether
20
−1.045
−0.310
−1.865
0.017
−2.429
−0.664
0.450
0.495
0.248
2060397
11488628

cholestan-3beta,5alpha,6beta-triol
20
−0.869
0.747
0.120
−0.575
1.000
0.815
0.382
0.523
0.074
2060399
11488442

18-aminoabieta-8,11,13-triene sulfate
20
−0.143
0.999
−0.762
−0.519
2.176
0.507
−0.727
−0.771
−0.462
2060400
11488230

5alpha-12-methoxy-4,4-bisnor-8,11,13-
20
−1.914
−0.133
−1.993
−0.939
0.625
−0.239
0.129
0.140
0.061
2060402
11488570

podocarpatrien-3-one

mucronulatol
20
1.396
−0.648
−0.847
0.006
−0.187
−0.365
−0.345
−0.104
−0.729
2060403
11489650

8-hydroxycarapinic acid
20
0.410
1.376
−0.475
1.077
0.309
0.767
−1.182
−1.218
−0.844
2060405
11488218

coumarinic acid methyl ether
20
−0.844
0.822
−2.099
−1.070
0.917
0.170
0.143
0.031
0.383
2060406
11488269

dimethylcaffeic acid
20
0.147
1.552
−1.206
−0.061
−0.142
0.804
−0.924
−0.838
−0.885
2060407
11488228

3beta-acetoxydeoxyangolensic acid, methyl
20
−0.316
0.081
−0.881
−0.388
−0.319
−0.069
0.772
0.446
1.332
2060408
11488201

ester

1-deacetoxy-1-oxo-3,7-dideacetylkhivorin
20
−0.413
−0.222
−1.776
−0.321
0.626
−0.411
−0.525
−0.704
−0.020
2060410
11488259

fisetinidol
20
−1.412
0.542
−1.804
−1.528
−0.215
0.234
−0.998
−1.107
−0.536
2060411
11488239

cholestanone
20
−0.208
1.206
−2.192
−1.065
1.864
0.272
0.165
0.147
0.214
2060413
11488432

6,7-dichloro-3-hydroxy-2-quinoxalinecarboxylic
20
0.109
0.893
−0.131
−0.521
0.666
0.217
−0.320
−0.313
−0.230
2060414
11488313

acid

2-mercaptobenzothiazole
20
−0.830
−0.408
−0.672
−0.486
0.354
−0.026
−0.211
−0.231
−0.097
2060416
11489482

tubaic acid
20
−0.569
0.416
0.150
−0.489
0.646
0.089
−0.746
−1.065
0.070
2060417
11489734

8,2′-dimethoxyflavone
20
−1.096
0.456
−0.556
1.282
1.219
0.864
−0.593
−0.414
−0.811
2060418
11488142

3beta-hydroxydeoxodihydrodeoxygedunin
20
−1.397
0.202
−0.656
1.048
1.488
0.142
−0.747
−0.849
−0.359
2060420
11488256

larixol
20
0.085
0.051
−0.221
−0.141
1.068
0.944
−0.507
−0.466
−0.552
2060421
11488133

2,4-dihydroxy-3,4-dimethoxy-4′-
20
−0.048
0.418
−1.130
0.089
−0.264
0.559
−1.530
−1.393
−1.568
2060422
11487979

ethoxybenzophenone

3alpha-hydroxy-4,4-bisnor-8,11,13-
20
0.056
−0.736
−0.574
−0.339
0.477
0.790
−0.250
−0.023
−0.717
2060424
11488117

podocarpatriene

dihydrogeduninic acid, methyl ester
20
0.488
0.519
−1.004
−0.571
0.820
0.117
0.739
0.881
0.289
2060425
11488577

2-methoxyresorcinol
20
0.514
0.150
0.266
−0.536
0.864
−0.146
0.218
−0.150
0.954
2060426
11489652

2-ethoxycarbonyl-2-
20
−0.703
0.391
−1.268
−0.404
0.483
0.521
0.003
0.155
−0.356
2060428
11489748

ethoxyoxaloyloxydihydrochrysin dimethyl ether

cymarin
20
−1.155
−0.332
−1.849
−0.996
0.695
0.356
−0.473
−0.412
−0.464
2060429
11488249

10-hydroxycamtothecin
20
−1.466
0.468
−2.588
0.725
−1.681
−2.397
−1.137
−1.180
−0.782
2060432
11489476

buddleoflavonoloside
20
0.169
0.643
0.006
0.050
0.265
0.736
0.073
0.114
0.017
2060433
11488447

6-acetoxyangolensic acid methyl ester
20
0.671
−0.780
−0.663
−0.055
1.137
−0.105
1.379
1.291
1.272
2060435
11488566

chaulmosulfone
20
−0.010
−0.078
−0.289
−0.993
0.935
−0.036
0.157
0.083
0.305
2060436
11489735

coenzyme Q10
20
0.166
0.525
−1.758
0.920
1.179
0.636
0.366
0.391
0.226
2060439
11488542

emodic acid
20
0.262
−0.639
−0.976
−0.966
1.403
0.505
−1.336
−1.210
−1.286
2060441
11488237

ethylnorepinephrine
20
−0.508
0.711
−1.017
−2.053
−0.396
−0.439
−0.475
−0.195
−0.921
2060442
11489460

theaflavanin
20
−1.349
1.006
−0.665
−2.074
−0.040
−0.166
−0.695
−0.764
−0.333
2060444
11488983

3beta-hydroxydeoxydesacetoxy-7-oxogedunin
20
0.688
0.198
−0.615
−0.064
0.662
0.306
−0.864
−1.027
−0.319
2060446
11488190

tetrahydrosappanone A
20
−0.222
−0.371
0.642
0.053
0.274
−0.187
−0.421
−0.737
0.337
2060448
11489736

crustecdysone
20
−0.458
0.693
−0.545
−0.721
0.657
0.468
0.354
0.487
0.062
2060451
11488288

quinamide
20
−0.397
1.161
−1.034
−0.518
0.405
0.359
−0.139
−0.529
0.735
2060452
11488238

tetrachloroisophthalonitrile
20
−5.297
−8.366
−6.675
−4.269
−3.975
−5.292
−3.510
−3.990
−1.780
2060453
11489465

hieracin
20
1.425
0.806
−0.557
−1.902
−0.329
0.057
−0.648
−0.421
−1.009
2060454
11488557

trimedlure
20
−0.267
1.437
−0.802
−0.630
0.458
0.122
−0.323
−0.291
−0.280
2060456
11488352

genkwanin
20
−0.323
0.957
−2.090
−0.491
3.337
−0.037
0.425
0.407
0.389
2060457
11489171

dipyrocetyl
20
0.452
1.278
−1.355
−0.363
1.260
0.865
−0.311
−0.242
−0.341
2060458
11488233

ancitabine
20
−0.655
−0.629
−2.731
−0.986
−0.189
−0.158
−1.115
−1.182
−0.726
2060459
11489470

isoduartin methyl ether
20
−0.603
0.032
−2.055
−0.777
0.599
0.882
−0.182
−0.008
−0.434
2060461
11488909

isotectorigenin, 7-methyl ether
20
0.633
−1.101
−1.606
0.574
0.644
−0.477
−0.592
−0.674
−0.360
2060463
11488033

tetrac
20
1.361
1.510
−0.677
−1.457
2.718
0.674
0.811
0.714
0.898
2060466
11488361

sappanone A trimethyl ether
20
−0.259
−0.015
−0.980
−0.290
0.120
−0.471
1.090
1.458
0.094
2060467
11489793

menthyl benzoate
20
−0.151
0.906
−1.026
0.016
1.375
−0.724
−0.115
0.047
−0.336
2060468
11488966

6alpha-methylprednisolone acetate
20
−0.480
0.169
−1.192
−0.462
0.321
−0.364
−0.130
−0.518
0.750
2060469
11488343

austricine
20
−0.394
0.158
−1.268
−0.711
0.665
0.842
0.165
0.081
0.349
2060471
11488292

canrenoic acid
20
−0.004
−0.434
−0.973
−0.749
0.803
0.732
0.072
0.154
−0.047
2060472
11488887

alpinetin methyl ether
20
0.220
0.801
−0.694
−0.286
0.827
−0.145
−0.565
−0.437
−0.717
2060475
11489173

chrysin dimethyl ether
20
−0.006
−0.343
−1.043
0.541
1.158
−1.016
0.480
0.444
0.470
2060475
11489175

leucomisine
16.24
−0.439
−0.558
−1.034
0.151
0.368
−0.568
−0.450
−0.405
−0.470
2060476
11468232

leucodin
20
−0.525
−1.027
−1.134
−0.355
0.695
−0.301
−0.300
−0.270
−0.261
2060476
11489473

mepartricin
20
−0.568
−0.392
−1.431
−0.309
−0.251
0.264
−0.710
−0.728
−0.464
2060478
11488950

N-acetylaspartic acid
20
−0.266
0.521
−0.456
−0.663
0.309
0.753
−0.670
−0.436
−1.046
2060483
11488608

acetylsalicylsalicylic acid
13.32
−0.840
1.663
−1.621
−0.808
0.399
−0.200
−0.301
−0.249
−0.389
2060486
11467246

diplosalsalate
20
−0.204
−0.137
−0.860
0.008
0.306
0.787
−1.001
−0.994
−0.766
2060486
11489480

(+)-linalool
20
−0.653
−0.323
−1.338
−0.810
0.481
0.690
−0.007
0.131
−0.342
2060488
11489760

selinidin
20
0.773
−0.419
−0.359
0.013
0.838
−0.478
−0.347
−0.328
−0.285
2060489
11488316

pteryxin
20
−0.681
−0.082
−1.515
0.300
1.106
0.711
−0.101
−0.097
−0.108
2060490
11488561

dihydrosamidin
20
0.476
0.085
−0.826
0.199
4.794
0.147
1.854
1.843
1.477
2060491
11488556

deoxysappanone B trimethyl ether
20
−0.068
1.619
−1.507
−0.194
1.064
0.336
0.993
1.050
0.613
2060494
11488003

2′,2′-bisepigallocatechin monogallate
20
0.442
0.545
−1.318
−2.350
0.428
0.246
−0.573
−0.545
−0.575
2060495
11487993

linamarin
20
0.796
0.025
−1.611
−0.333
−0.189
−0.052
−1.024
−0.847
−1.232
2060497
11489788

apiin
20
−0.631
−0.267
−1.444
0.029
0.322
−0.697
−0.032
−0.150
0.250
2060499
11489616

felamidin
20
0.224
0.238
−0.475
0.600
0.710
0.921
0.966
0.835
1.050
2060501
11488547

acetosyringone
20
−0.432
0.040
−1.266
−0.370
0.269
0.310
0.029
−0.040
0.201
2060502
11488245

(−)-asarinin
20
−0.632
0.276
−0.505
−0.439
−0.229
0.607
−1.167
−0.726
−1.858
2060503
11488627

3-methylorsellinic acid
20
−0.494
1.932
−1.253
−0.030
0.860
0.321
−1.005
−1.318
−0.108
2060504
11488229

dihydrolonchocarpenin
20
−0.698
−0.259
−0.977
0.277
0.860
0.022
−0.672
−0.562
−0.680
2069224
11488980

theaflavin digallate
20
−1.408
1.490
−0.518
−0.326
0.718
0.601
0.783
0.948
0.275
2069225
11488461

dehydrovariabilin
20
0.309
−0.517
−1.225
0.951
0.167
0.043
0.367
0.277
0.416
2069226
11487874

2-methoxyxanthone
20
−0.428
−0.087
−1.044
0.540
1.398
1.007
−0.467
−0.710
0.165
2069228
11488241

2-hydroxyxanthone
20
−0.402
−0.916
−1.863
−0.245
1.660
0.238
−0.364
−0.173
−0.652
2069229
11489538

chlorpheniramine
20
0.292
−0.163
−0.875
−0.443
1.228
0.766
0.089
0.043
0.103
2069230
11487972

3-prenyl-4-hydroxyacetophenone
20
−0.696
1.387
−1.066
−0.010
2.418
0.220
0.607
0.477
0.804
2069231
11488405

estriol methyl ether
20
0.054
−0.115
−1.611
−0.046
0.299
0.241
−0.432
−0.309
−0.643
2069233
11487827

(+)-bicuculline
20
−0.572
0.790
−0.812
−0.945
0.428
−0.116
−0.189
−0.028
−0.495
2069234
11488533

1,4,5,8-tetrahydroxy-2,6-
20
−0.853
−0.346
−0.344
−0.662
0.772
0.005
−1.123
−1.178
−0.739
2069239
11489566

dimethylanthroquinone

tetrahydrocortisone-3,21-diacetate
20
−0.030
0.067
−0.664
0.074
0.456
−0.397
−0.320
−0.558
0.269
2069240
11489642

estradiol methyl ether
20
0.510
0.823
−0.685
−0.007
0.411
1.670
0.099
0.214
−0.209
2069241
11487828

3,5-diprenyl-4-hydroxyacetophenone
20
−0.293
−0.362
−0.582
−0.022
1.014
−0.220
0.149
−0.036
0.538
2069242
11488425

2′,beta-dihydroxychalcone
20
−0.801
−0.920
−1.791
−0.044
0.194
−0.260
0.097
−0.188
0.600
2069243
11488032

norstictic acid
20
0.730
0.430
−0.613
−0.628
−0.426
0.467
−0.800
−0.639
−1.023
2069246
11487987

retusin 7-methyl ether
20
−0.245
−0.148
−0.627
−0.603
0.088
0.412
0.788
0.765
0.631
2069249
11487871

avocadyne
20
−0.546
−0.278
−0.646
−0.029
0.611
−0.049
−1.062
−1.019
−0.897
2069250
11488344

1,3-dideacetylkhivorin
20
0.507
0.959
−0.622
0.051
0.963
0.887
−0.693
−0.349
−1.275
2069251
11488567

prieuranin acetate
20
1.518
1.574
−0.879
−0.074
−0.400
0.615
−1.113
−0.904
−1.381
2069252
11488059

bussein
20
−0.052
0.214
−0.599
−0.807
0.656
0.622
−0.809
−0.683
−0.868
2069253
11488438

lobaric acid
20
0.082
−0.552
−0.427
−0.164
0.860
−0.020
−0.455
−0.499
−0.343
2069254
11488126

irigenol
20
0.249
0.611
−0.810
−0.374
−1.001
0.410
−1.274
−0.838
−1.938
2069255
11488617

6-methoxyprosogerin B diethyl ether
20
−0.627
−0.465
−1.860
0.708
−1.331
0.479
1.074
0.750
1.499
2069256
11488571

isokobusone
20
−0.090
−0.166
−0.507
−0.283
−0.201
0.480
−0.848
−0.813
−0.713
2069257
11489589

koparin 2′-methyl ether
20
0.024
−0.071
−0.532
−0.442
0.126
0.007
−1.151
−1.461
−0.309
2069258
11488629

epiandrostanediol
20
1.143
1.132
−0.207
−0.156
0.113
−0.201
−0.069
−0.203
0.190
2069259
11488625

rutilantinone
20
0.192
−2.936
−2.979
−3.758
2.445
0.372
−1.917
−1.152
−3.039
2069260
11488268

alpha-toxicarol
20
0.304
−2.946
−1.982
0.820
0.101
−2.637
−0.046
0.124
−0.345
2069261
11489649

3,4,5-trimethoxycinnamaldehyde
20
1.061
0.145
1.043
0.647
−0.228
−0.808
−0.523
−0.724
0.025
2069262
11489656

5alpha-androstan-3beta,17beta-diol
20
−0.204
0.359
−0.454
−1.116
0.607
0.280
0.123
0.059
0.270
2069264
11488427

5alpha-androstan-3,17-dione
20
−0.579
−0.192
−0.601
0.107
0.649
0.048
−0.499
−0.426
−0.509
2069265
11488196

ephedrine
20
−0.536
−1.049
−2.342
−0.834
1.633
0.077
−0.074
−0.100
−0.056
2069266
11487953

praesterone acetate
20
1.018
0.585
1.084
1.329
0.054
−0.521
−0.532
−0.477
−0.457
2069268
11488946

allodeoxycholic acid
20
−1.161
−1.212
−2.126
0.404
−0.164
−2.903
−0.905
−0.903
−0.773
2069269
11489768

5alpha-cholestan-3beta-ol-6-one
20
−0.430
2.248
0.811
0.479
0.397
1.006
−0.731
−0.603
−0.862
2069270
11488620

1S,2R-phenylpropanolamine
20
0.296
−0.204
−1.507
−0.137
0.721
0.280
−0.539
−0.484
−0.598
2069271
11487832

lycopodine
20
−0.466
−0.283
−1.139
−0.239
0.500
−0.093
−0.150
−0.028
−0.411
2069272
11489810

chondrosine
20
−0.800
0.150
−1.759
−1.001
0.741
0.040
−0.743
−0.782
−0.476
2069273
11488422

haematoporphyrin
20
−1.933
−0.917
−3.312
−3.662
1.666
0.324
0.309
0.251
0.416
2069274
11488252

glycyrrhizic acid
20
0.254
1.266
−0.746
−0.606
0.578
0.339
−0.424
−0.227
−0.753
2069275
11489197

irigenin, dibenzyl ether
20
−1.724
0.867
−0.793
0.178
0.088
0.012
−0.325
−0.163
−0.602
2069276
11488490

haematommic acid
20
−0.412
2.409
−0.740
0.002
−1.077
0.631
−0.410
−0.078
−1.067
2069278
11489738

N-methylisoleucine
20
1.026
−0.463
0.372
−0.210
0.300
−0.451
0.772
0.676
0.850
2069279
11489655

isopeonol
20
−1.180
2.649
−0.831
0.271
−0.219
0.734
−0.109
0.134
−0.635
2069280
11489740

estrone benzoate
20
0.154
0.592
−0.807
−0.277
0.210
0.406
0.061
0.190
−0.179
2069281
11489603

naproxol
20
0.249
0.350
−1.522
−0.500
−0.319
0.993
−0.895
−1.214
−0.018
2069284
11488310

arthonioic acid
20
−0.413
−0.458
−2.597
−0.493
1.167
−0.019
−0.668
−0.590
−0.657
2069285
11489540

ergosta-7,22-dien-3-one
20
−0.892
0.167
−2.474
−0.544
0.912
0.221
−0.708
−0.764
−0.415
2069286
11489559

dihydrojasmonic acid, methyl ester
20
0.971
−0.049
−0.452
−0.204
−0.386
−0.281
0.948
0.831
1.068
2069287
11488374

2,3-diacetoxy-7,8-epoxy-24,29-dinor-1,3,5-
20
0.270
1.817
−0.165
−1.396
−0.501
−0.661
−0.993
−0.774
−1.269
2069289
11488529

friedelatriene-20-carboxylic acid

picropodophyllotoxin
20
−0.107
−0.952
−2.402
−0.349
−1.202
−1.445
1.512
1.581
1.129
2069291
11488336

bisanhydrorutilantinone
20
−0.493
0.217
−1.755
−2.223
0.236
0.148
−0.727
−0.268
−1.532
2069293
11488469

candesartan cilextil
20
1.842
0.721
−1.116
−0.743
1.855
1.328
−0.432
−0.259
−0.658
2069295
11488301

cholesteryl acetate
20
−1.471
0.018
−2.138
−0.657
0.524
0.097
0.228
0.273
0.142
2069297
11489613

acetriazoic acid
20
0.205
−0.024
−0.938
−0.059
1.158
−1.416
−0.710
−0.870
−0.320
2069298
11487844

methyl 3beta,12-dihydroxy-11-
20
−0.315
−0.092
−1.387
−0.760
0.918
−0.005
−0.063
0.054
−0.217
2069303
11489068

ketoisoallospirostan-3-hemisuccinate

androsta-1,4-dien-3,17-dione
20
0.162
−0.063
−0.500
0.152
0.068
0.261
−0.180
−0.143
−0.189
2069306
11489639

derrubone
20
−0.568
−3.786
−0.499
−1.272
1.419
−0.126
−0.409
−0.626
0.066
2069308
11487864

beta-dihydrorotenone
20
−0.184
−2.497
−2.771
1.079
0.122
−0.408
−0.818
−0.828
−0.695
2069309
11488002

5,7-dimethoxyisoflavone
20
−0.298
−0.194
−1.335
−0.235
0.573
0.046
0.945
0.916
0.773
2069315
11487861

tyrphostin B44
20
−0.628
−0.184
−0.858
−0.075
−0.132
−1.355
−0.751
−0.794
−0.481
2069318
11489626

sinapic acid methyl ether
20
−0.934
0.600
−0.736
−0.716
0.722
0.207
−1.103
−1.058
−1.015
2069324
11489771

juarezic acid
20
−0.106
0.624
−0.449
−0.821
0.345
−0.113
−0.147
0.108
−0.650
2069325
11488633

obtusaquinone
20
−4.658
−8.654
−6.409
−3.829
−1.119
−5.381
ND
ND
ND
2069327
11488111

ginkgetin
20
−1.523
−2.623
−3.855
−4.324
−1.347
−3.027
−2.228
−2.585
−1.101
2069329
11487870

flavokawain B
20
0.583
0.641
−0.298
−0.302
0.292
0.708
−1.453
−1.423
−1.291
2069330
11487992

stigmasta-4,22-dien-3-one
20
0.023
0.796
−1.294
−0.299
0.550
0.434
−0.138
−0.094
−0.118
2069333
11488954

suprofen methyl ester
20
0.611
0.771
−1.160
0.577
0.591
−0.191
0.139
0.216
−0.048
2069337
11489182

epicatechin
20
−1.380
0.949
−1.915
−2.452
−0.465
0.110
0.431
0.310
0.641
2069338
11488281

2-benzoyl-5-methoxybenzoquinone
20
−0.284
0.353
−1.489
−0.229
−0.542
0.206
−0.699
−0.511
−0.985
2069342
11489747

1s,9r-hydrastine
20
0.650
0.403
−0.539
−0.849
−0.029
0.359
−0.152
−0.041
−0.341
2069343
11489157

prednisone
11.16
−1.668
0.358
−1.206
−0.474
0.623
−0.428
−0.315
−0.432
−0.048
2080073
11467225

hydrocortisone
11.04
−0.976
0.175
−0.928
−0.266
0.501
−0.579
−0.787
−0.823
−0.552
2080102
11467595

cyclopiazonic acid
20
−1.392
−0.353
−1.107
0.863
−0.293
0.033
0.186
0.163
0.172
2080198
11488612

sisomicin
8.94
−0.274
0.411
−1.515
−0.962
1.889
0.746
−0.448
−0.337
−0.588
2080587
11467654

cycloheximide
14.22
−2.540
−1.021
−3.550
2.318
−3.415
−1.378
−0.504
1.354
−4.179
2080598
11467938

cycloheximide
20
−2.804
−0.704
−3.499
2.759
−2.628
−2.123
−1.482
0.688
−5.637
2080598
11488716

halofantrine
8
0.132
−0.166
−0.174
−0.668
0.012
−0.236
−0.508
−0.239
−0.969
2080909
11468179

fluorometholone
10.62
−0.965
−0.458
−1.306
−0.299
2.141
−0.324
0.446
0.038
1.187
2081008
11467866

helenine
20
−4.599
−8.064
−6.498
−3.676
−2.409
−5.312
−2.156
−2.240
−1.624
2081025
11488113

cimetidine
20
−1.404
0.336
−1.571
−0.482
0.193
0.794
−0.252
−0.460
0.208
2081029
11488598

amphotericin B
4.32
1.210
0.880
−0.790
0.308
0.005
−0.982
−0.046
0.181
−0.507
2081486
11467558

farnesol
20
−1.327
0.026
−1.554
−0.153
0.550
−0.437
−0.066
0.106
−0.401
2081691
11489213

rilmenidine
22.2
0.245
0.135
0.082
−0.589
0.340
−0.042
0.123
0.319
−0.313
2098610
11468130

lithocholic acid
10.62
0.256
−1.002
−1.419
−0.283
0.353
−0.030
0.002
0.248
−0.491
2105063
11467944

celastrol
20
−4.797
−8.640
−6.584
−3.520
−2.732
−5.979
ND
ND
ND
2114344
11487966

daunorubicin
7.58
−3.547
−4.649
−5.009
−2.337
−2.398
−3.722
−1.008
−2.094
1.373
2117312
11467635

strophanthidin
9.88
−0.448
−0.236
−0.908
−0.175
0.947
0.287
−0.590
−0.729
−0.190
2117332
11467858

4-aminoantipyrine
4.42
0.530
−1.148
−1.470
−4.045
0.564
0.087
−0.182
−0.041
−0.450
2117409
11467573

pimozide
8.66
0.494
−0.856
−0.375
−0.170
2.196
−0.531
−0.548
−0.438
−0.648
2117626
11467456

pimozide
20
0.146
−0.464
−0.447
−0.381
1.432
−0.121
0.722
0.857
0.386
2117626
11488842

anisomycin
15.08
−2.835
−1.426
−4.623
−1.537
−2.958
−2.841
−0.353
1.256
−3.545
2117676
11467560

ergosterol
20
−0.792
−0.762
−1.864
−0.489
−0.198
0.386
0.231
0.420
−0.240
2120750
11488017

metixene
12.92
1.221
−1.165
−0.786
−0.713
−0.834
0.097
−1.190
−1.058
−1.236
2120971
11467639

biperiden
12.84
0.740
1.599
−0.886
−0.517
2.725
0.053
−0.817
−0.496
−1.312
2121358
11467650

iohexol
4.88
−0.374
0.395
−1.085
−0.970
0.568
0.080
−0.434
−0.312
−0.598
2141046
11467660

riboflavin
20
0.590
−0.150
−0.732
−0.442
4.295
−0.667
0.626
0.483
0.774
2141061
11488476

sinomenine
20
−0.937
0.495
−1.489
−0.657
0.777
−0.117
−0.875
−0.565
−1.253
2141064
11489058

yohimbine
11.28
−0.860
−0.305
−1.915
−1.197
0.159
0.699
−0.041
0.169
−0.471
3000363
11467732

dantrolene
20
−0.497
0.634
−0.490
−0.080
0.712
−1.219
0.160
0.159
0.210
3000787
11488996

(S)-propranolol
15.42
0.307
0.430
−0.351
−0.340
−0.185
0.349
0.857
0.623
1.161
3002368
11468229

furazolidone
17.76
0.828
1.071
−1.254
−0.233
−0.319
−0.368
−0.983
−0.781
−1.207
3043753
11467956

furazolidone
20
−0.411
1.326
−1.256
−1.059
0.761
0.881
−0.133
−0.040
−0.228
3043753
11488831

guanabenz
20
−0.404
1.035
−0.886
−1.073
1.527
0.420
−0.428
−0.286
−0.563
3044526
11488930

trimeprazine
8.92
0.760
−0.459
−2.221
−0.821
1.314
−2.786
−0.942
−0.936
−0.778
3044756
11467990

trimeprazine
20
−1.472
−3.762
−2.227
1.905
−0.430
−0.086
−0.013
−0.130
0.208
3044756
11488774

guanidine carbonate
20
−0.835
−0.171
−0.683
−0.252
0.401
−1.206
−1.142
−1.112
−0.993
3044782
11488665

compactin
20
−0.454
−0.561
−0.569
0.369
−1.309
−0.971
−0.154
−0.217
−0.027
3045136
11489795

ipratropium
20
−0.962
1.230
−0.600
−0.508
1.245
0.049
−0.294
−0.091
−0.570
3045140
11489091

amoxicillin
20
−1.400
−0.033
−1.357
−0.867
1.061
0.351
0.741
0.607
0.815
3045196
11487961

dexamethasone
20
−0.392
0.221
−1.719
0.240
−0.512
−0.235
−0.339
−0.318
−0.250
3045298
11488942

cyproterone
20
0.014
0.856
0.079
−0.962
1.155
0.548
−0.490
−0.461
−0.446
3045655
11489413

metaraminol
20
0.107
1.865
−1.268
−0.772
0.313
0.327
−0.589
−0.456
−0.745
3045662
11489358

pentolinium
10.24
0.213
1.449
0.254
−0.024
3.608
0.387
0.521
0.489
0.444
3045683
11467336

pentolinium
20
−0.568
0.247
−0.771
0.209
0.392
−0.703
−1.000
−0.840
−1.080
3045683
11489417

famotidine
20
−0.793
1.389
−0.762
−0.445
1.272
−0.339
0.514
0.591
0.334
3045799
11488852

halcinonide
20
0.106
−0.401
−0.789
0.570
0.624
−0.794
0.492
0.284
0.831
3046112
11489356

avermectin B1
20
0.129
−0.108
−0.284
−0.336
2.442
0.116
0.198
0.170
0.295
3046211
11488895

lindane
20
−0.322
0.025
−1.788
−0.724
2.681
0.467
−0.629
−0.628
−0.474
3046265
11489680

testosterone propionate
20
−1.758
0.781
−1.449
−0.365
1.034
−0.996
−1.608
−1.410
−1.619
3046390
11489062

phentolamine
14.22
−0.525
−0.486
−0.112
−0.548
0.893
−0.141
−0.165
−0.236
−0.026
3046406
11467378

mitomycin C
20
−1.520
0.878
−1.986
−0.282
−1.187
−1.740
−0.139
0.005
−0.430
3046992
11488736

bisabolol
20
0.129
−0.136
−1.329
0.164
1.461
0.068
−0.205
−0.275
0.008
3053888
11489601

cedrol
20
−0.226
0.003
−0.896
0.175
0.096
−0.218
−0.319
−0.249
−0.351
3053889
11489602

aconitic acid
20
0.322
1.106
−0.544
−0.030
0.839
−1.099
−0.886
−0.951
−0.538
3053891
11489604

allopregnanolone
20
0.743
0.263
0.733
0.732
1.285
1.264
−0.021
0.077
−0.274
3053987
11488086

euphol
20
0.693
−0.327
−0.521
1.283
−0.234
−0.662
−0.661
−0.754
−0.405
3054028
11487986

pinosylvin
20
−0.614
0.027
−1.343
−0.444
−0.927
0.602
−0.409
−0.198
−0.802
3054030
11488009

violastyrene
20
−0.886
−0.880
−1.761
−0.080
−0.141
0.063
−0.800
−0.674
−0.947
3054032
11488011

nerolidol
20
−0.629
−0.121
−1.158
−0.552
0.392
−0.236
−0.170
−0.188
−0.092
3054057
11489323

chaulmoogric acid
20
0.156
0.746
−1.195
−0.173
0.706
0.264
−0.255
−0.059
−0.539
3054072
11489038

stigmasterol
20
−0.336
−0.213
−1.330
−0.621
−0.227
0.442
−0.522
−0.467
−0.488
3054095
11489449

tigogenin
20
−0.452
−0.530
−1.580
−0.277
1.151
−0.049
−0.118
−0.105
−0.177
3054097
11488093

xanthopterin
20
−1.031
1.368
−0.844
0.187
0.799
0.798
−0.343
0.237
−1.465
3054108
11488459

anthothecol
20
−4.715
−8.676
−6.566
−3.669
−3.614
−6.072
ND
ND
ND
3054122
11488041

crinamine
20
−2.147
0.593
−4.403
0.043
−2.125
−0.619
0.628
2.270
−2.895
3054128
11488098

ambelline
20
−0.302
0.086
−1.389
0.246
0.774
−0.311
−0.823
−1.011
−0.330
3054129
11488015

euphol acetate
20
−1.099
0.149
−1.087
0.066
0.660
−0.739
−1.280
−1.298
−0.951
3054130
11488176

beta-amyrin
20
−0.235
0.506
−1.204
−1.039
−0.089
0.610
0.371
0.459
0.146
3054135
11488169

beta-amyrin
20
−0.096
0.910
−1.893
−0.598
1.276
0.329
0.119
0.263
−0.128
3054136
11489069

corynanthine
20
0.214
1.318
−0.721
−0.032
0.470
0.397
−0.955
−1.008
−0.672
3054270
11489188

ursolic acid
20
−2.670
−0.787
−2.032
−0.737
−0.795
0.191
−0.759
−0.718
−0.652
3054523
11489560

oleanolic acid
20
0.061
0.521
−1.409
−0.480
0.500
0.866
0.105
0.081
0.071
3054572
11488109

scandenin
20
−0.337
−0.093
−0.897
−0.508
0.767
0.268
−0.079
0.284
−0.745
3054634
11489722

cholecalciferol
20
0.201
0.289
−0.433
0.185
1.221
0.110
−0.138
−0.261
0.137
3054675
11489185

deoxysappanone B 7,3′-dimethyl ether acetate
20
0.301
0.598
−1.919
−0.107
−1.894
−1.602
0.097
−0.156
0.544
3054809
11487995

corticosterone
11.54
−0.693
0.075
−1.282
0.088
0.126
−0.379
−0.358
−0.282
−0.446
3054850
11467580

quinic acid
20
0.174
−0.385
−0.580
0.145
1.099
−0.402
−0.057
−0.065
0.010
3054971
11489606

abietic acid
20
0.225
0.173
−0.406
−0.311
−0.126
−0.410
0.268
0.264
0.229
3054972
11489314

ajmalicine
11.34
−0.201
0.822
−1.608
−0.826
0.948
0.251
−0.178
−0.210
−0.081
3054974
11467740

menthone
20
0.344
1.509
−0.587
−0.519
−0.339
0.423
−0.611
−0.169
−1.418
3054976
11488507

deoxyadenosine
20
0.279
0.471
−0.133
−0.458
−0.575
0.271
0.250
0.366
−0.033
3054980
11489317

acacetin
20
−0.687
−0.691
−0.727
0.032
0.048
0.531
−1.020
−0.999
−0.919
3054981
11488008

mifepristone
9.32
−0.149
−0.183
−0.918
−0.201
1.602
−1.159
0.282
0.143
0.506
3055129
11467447

pristimerol
20
−5.551
−6.511
−5.956
−3.658
−0.368
−6.066
−2.500
−2.190
−2.630
3055171
11488528

pinosylvin methyl ether
20
−0.471
−0.538
−0.867
−0.451
0.042
0.368
−0.304
−0.390
−0.112
3055207
11488010

ascorbic acid
20
0.198
0.527
−0.653
0.212
−0.048
−1.661
0.027
−0.014
0.055
3055218
11489764

coniine
20
−0.475
0.491
−1.000
−0.564
0.659
−0.425
0.008
0.035
−0.084
3055245
11489782

dalbergione
20
−0.865
0.685
−2.448
−0.586
−0.629
−1.116
−0.176
−0.010
−0.396
3055248
11488974

acrisorcin
20
−4.510
0.461
−2.420
−0.408
0.053
−0.132
0.399
0.810
−0.434
3055280
11488923

uvaol
20
−0.873
0.124
−0.714
−0.266
0.662
−0.846
−0.626
−0.531
−0.641
3055306
11489456

loganin
20
−0.968
0.561
−1.114
−0.744
0.441
0.272
−0.299
−0.206
−0.391
3055308
11489453

bergenin
20
−0.657
0.395
−1.153
−0.254
0.647
−0.039
−0.338
−0.230
−0.443
3055310
11488416

triptonide
20
−3.627
−5.120
−4.144
−2.417
−2.071
−4.153
0.149
−2.183
5.015
3055313
11488293

cholic acid
20
−1.325
−0.370
−1.806
−0.579
0.950
0.514
−0.250
−0.272
−0.115
3055321
11488420

thioxolone
20
−0.135
−0.107
−1.399
−2.030
0.060
−0.199
−0.012
−0.179
0.374
3055336
11488266

curcumin
20
−0.722
1.107
−2.170
−2.198
−0.642
−0.468
−0.575
−0.300
−0.982
3055363
11489530

gangleoidin acetate
20
−0.001
−0.292
−0.705
−0.785
0.114
−0.136
−0.602
−0.560
−0.509
3055370
11488979

marmesin
20
0.129
0.172
−1.130
−0.945
0.854
0.834
0.519
0.597
0.237
3055383
11488553

cosmosiin
20
−0.513
0.932
−0.677
−0.907
1.120
0.144
−0.613
−0.648
−0.382
3055391
11489568

lupinine
20
0.417
0.645
−0.980
0.039
0.444
−0.249
−0.804
−0.723
−0.769
3055414
11488315

marmesin acetate
20
0.976
0.720
−1.647
−0.592
0.641
0.449
0.025
0.221
−0.308
3055445
11489028

epicoprosterol
20
−1.124
0.257
−1.568
−1.063
0.312
−0.025
0.086
0.230
−0.186
3055472
11489452

anethole
20
−0.309
0.204
−1.000
−0.720
0.097
−0.161
−0.431
−0.682
0.215
3055475
11488354

nicotinyl tartrate
20
−0.406
1.071
−0.727
−0.611
0.550
−0.048
−0.218
−0.313
0.057
3055569
11489546

inosine
20
0.264
0.379
−0.337
−0.630
0.851
0.121
−0.339
−0.457
−0.056
3055573
11489755

sparteine
20
−0.501
1.073
−0.554
1.223
0.700
0.518
−0.203
−0.149
−0.295
3057756
11488537

sparteine
20
−0.526
−0.130
−1.158
−0.676
1.118
−0.037
−1.464
−1.473
−1.212
3057756
11489790

chlorotrianisene
10.5
−1.153
0.419
−1.139
−0.487
1.360
0.165
−0.478
−0.328
−0.693
3057880
11467905

chlorotrianisene
20
0.118
0.354
0.277
−0.360
0.945
0.794
−0.538
−0.382
−0.764
3057880
11488520

sulpiride
20
−1.524
−0.188
−1.375
−0.612
0.562
−0.068
−0.227
−0.183
−0.265
3058009
11489240

methoxamine
18.94
−0.871
−0.387
−1.537
−0.655
1.380
1.668
0.022
0.262
−0.467
3058468
11467683

methoxamine
20
−1.522
−0.205
−1.209
−1.270
1.719
−0.125
−0.825
−0.756
−0.827
3058468
11488592

alpha-hyodeoxycholic acid
20
−1.074
−0.154
−0.797
−0.678
0.184
0.106
−0.737
−0.620
−0.868
3058484
11489767

(−)-deguelin
20
−0.940
−5.123
−4.052
1.451
0.426
−1.865
−1.423
−1.606
−0.834
3058525
11488114

estrone
20
0.054
0.623
−0.937
−0.532
0.385
0.076
−0.251
−0.031
−0.584
3058535
11488850

ergonovine
20
−0.536
1.630
−0.529
0.139
0.104
0.826
−0.231
−0.113
−0.491
3058614
11487820

naringin
20
0.198
0.672
−0.963
0.746
1.074
0.127
0.054
0.120
−0.097
3058615
11489181

piscidic acid
20
−0.160
0.136
−1.141
−0.632
0.364
−0.241
−0.512
−0.613
−0.255
3058620
11488023

solasodine
20
−0.392
1.605
−0.747
−0.407
0.797
0.280
−0.330
−0.296
−0.293
3058621
11488163

brazilein
20
−1.633
0.713
−0.725
−0.110
1.078
−1.301
1.041
1.169
0.556
3058622
11488526

androsterone
20
0.953
0.035
0.058
0.163
0.247
0.192
0.128
0.133
0.031
3058740
11487968

spironolactone
20
−0.957
1.029
−0.765
−1.347
0.697
−0.171
0.377
0.249
0.571
3059108
11489132

cholestan-3-one
20
−1.020
0.144
−1.121
−0.585
0.836
0.435
0.246
0.144
0.353
3059164
11489769

dioxybenzone
16.38
−0.704
0.981
−0.414
−0.444
1.241
0.256
−0.840
−0.750
−0.900
3059213
11468046

dioxybenzone
20
0.295
0.629
−0.314
−0.080
0.459
0.684
0.924
0.963
0.741
3059213
11488848

estradiol propionate
20
−0.359
0.733
−0.310
−1.076
0.717
0.651
0.042
0.036
0.052
3059431
11489252

7-oxocholesterol
20
0.614
0.694
0.024
0.913
0.692
1.259
−0.675
−0.697
−0.453
3059432
11488381

estradiol acetate
20
0.983
0.847
−1.085
1.098
1.047
−0.085
0.316
0.339
0.141
3059433
11487826

kobusone
20
0.754
0.341
−0.669
−0.231
0.715
0.388
0.879
0.721
0.952
3059434
11488131

chloramphenicol
20
0.340
0.966
−1.003
−0.910
0.096
0.205
−0.747
−1.154
0.219
3059437
11488700

aphyllic acid
20
−0.337
−0.820
−1.304
0.649
0.837
1.013
0.694
0.936
0.045
3059440
11488541

orlistat
20
2.525
0.960
0.847
0.306
1.029
−0.233
0.056
−0.005
0.199
3059445
11489494

cefdinir
20
0.174
−0.201
−0.929
−0.343
0.833
1.025
−0.047
−0.008
−0.091
3059465
11489501

ceftibuten
20
−0.394
1.208
−0.776
0.264
1.538
0.063
−0.061
−0.153
0.166
3059791
11489500

valsartan
20
−0.540
0.559
0.346
−0.198
0.816
0.174
−0.818
−0.894
−0.435
3059817
11488936

vidarabine
14.96
−1.004
−0.331
−1.667
−0.335
0.404
−0.784
−0.879
−0.885
−0.698
3060003
11467916

idazoxan
19.58
−0.270
0.477
−0.656
−0.281
−0.076
−0.533
0.975
0.876
0.990
3060036
11468074

estrone
14.8
−0.739
0.498
−0.632
0.063
0.272
0.360
0.104
−0.108
0.512
3060043
11468062

guanabenz
17.32
0.167
0.774
−0.950
−1.001
0.878
0.726
0.197
−0.043
0.591
3060090
11467244

ketoconazole
7.52
−0.490
−0.467
−0.448
0.304
1.572
0.406
0.527
0.701
0.073
3060108
11467537

DO 897/99
9.58
0.519
−1.132
−0.446
0.416
0.511
0.327
0.520
0.276
0.924
3060137
11467707

budesonide
9.3
−1.282
−0.421
−1.390
−1.016
0.648
−0.730
0.532
0.578
0.335
3060147
11467666

iobenguane sulfate
14.54
1.366
−1.160
−0.971
0.229
−1.253
0.392
0.637
0.845
0.080
3060173
11467638

(S)-methoprene
20
−1.056
0.724
−1.068
−0.804
0.171
0.097
0.202
0.107
0.341
3060195
11488521

moxifloxacin
20
−0.374
0.970
−0.915
−0.680
−0.326
0.145
−0.720
−0.794
−0.386
3060196
11488339

cefotaxime
8.78
−0.254
0.371
−0.793
−0.037
0.239
−0.624
0.243
0.232
0.176
3060388
11467287

doxepin
14.32
0.584
−0.076
−1.279
−0.780
0.478
1.151
−0.746
−0.608
−0.886
3060494
11467411

scopolamine
13.18
−0.789
−0.912
−1.072
−0.784
0.081
0.260
−0.078
−0.051
−0.121
3060919
11468025

lobeline
11.86
−0.381
−0.165
−1.496
−1.248
1.284
0.619
−0.216
−0.012
−0.606
3061052
11467733

4-aminocrotonic acid
20
−0.667
1.062
−0.862
−0.614
−0.398
0.446
−0.542
−0.579
−0.360
3061087
11489289

ketanserin
7.34
−0.527
−0.388
−0.448
−0.581
0.083
−0.247
0.275
0.336
0.093
3061431
11467540

xamoterol
11.78
0.153
0.495
−0.899
−0.528
0.274
0.281
−0.178
−0.078
−0.359
3061617
11468071

cytochalasin E
20
−0.980
2.747
−2.467
−0.864
−2.109
−3.335
1.353
1.449
0.973
3063989
11489056

isoflupredone acetate
9.52
−1.329
−0.025
−0.188
0.397
0.011
0.267
0.181
0.341
−0.221
3064163
11467154

dantrolene
12.72
0.272
0.077
−1.537
−0.516
0.214
0.359
−0.769
−0.514
−1.138
3068677
11467439

benzydamine
12.92
−0.074
−0.703
0.120
−0.141
0.426
0.052
0.560
0.470
0.639
3068682
11467445

norcyclobenzaprine
15.3
−0.369
−1.466
−2.283
−0.427
0.956
−0.724
−0.440
−0.328
−0.586
3068692
11467661

imipenem
13.36
−0.973
0.250
−0.777
−0.461
0.790
−0.330
−0.495
−0.319
−0.755
3068724
11467667

L-methionine sulfoximine
22.2
−0.928
0.202
−1.902
−0.703
0.762
−0.412
−0.766
−0.620
−0.913
3068727
11467671

triflusal
16.12
−1.375
−0.004
−0.432
−0.592
1.275
−0.003
−0.390
−0.401
−0.292
3068731
11467676

clorsulon
10.5
−0.111
−0.210
−0.774
−0.647
1.055
−0.186
0.240
0.394
−0.125
3068774
11467688

pregnenolone
12.64
−0.330
0.824
0.061
0.542
1.242
0.404
0.250
0.185
0.345
3068775
11467694

dihydroergotoxine
7.1
−0.119
1.009
−0.443
0.046
0.218
0.576
−0.087
−0.053
−0.139
3068781
11467717

lincomycin
9.84
−0.258
0.766
−0.935
−0.749
0.331
0.288
−0.689
−0.716
−0.492
3068878
11467450

phenylpropanolamine
26.46
−0.373
1.781
−0.396
−0.650
0.552
0.947
0.487
0.541
0.267
3068879
11467472

ascorbic acid
22.46
−0.040
0.900
−1.280
0.503
0.350
0.380
−0.141
−0.115
−0.170
3068880
11467473

zaprinast
14.74
−0.634
1.014
−1.911
−0.704
1.895
−0.302
0.224
0.330
−0.027
3068881
11467483

chlorprothixene
12.66
0.574
0.645
−0.544
0.089
1.237
−1.373
0.206
0.112
0.358
3068882
11467496

adenosine 5′-monophosphate
11.52
−1.097
0.061
−1.214
−0.915
1.276
0.104
−0.137
−0.195
0.005
3068883
11467504

betamethasone
10.2
−0.479
−0.371
−1.315
−0.688
0.846
−0.822
0.298
0.178
0.490
3068885
11467510

clofazimine
8.44
−1.383
−0.999
−1.191
0.552
1.422
0.320
−0.358
−0.184
−0.640
3068886
11467524

amikacin
6.84
−1.029
−0.026
−0.942
−0.723
1.056
0.015
0.831
0.438
1.480
3068923
11467543

clomiphene
9.86
−0.620
0.022
−0.400
−0.755
1.587
0.699
0.461
0.354
0.593
3068926
11467545

sulfaguanidine
18.68
0.216
2.181
0.059
0.511
0.379
0.509
0.738
0.787
0.437
3068956
11467158

idoxuridine
11.3
0.295
0.995
−0.131
−0.167
1.086
0.916
−0.548
−0.456
−0.662
3068957
11467166

captopril
17.3
0.347
0.600
−0.646
−0.783
1.363
0.551
0.773
0.799
0.522
3068958
11467167

cimetidine
15.86
−1.323
−0.082
−1.129
−0.952
1.066
0.587
0.216
0.365
−0.164
3068961
11467174

betazole
35.98
−0.554
0.135
−1.681
−0.798
1.677
−0.746
−1.100
−1.056
−1.020
3068964
11467191

SR-95639A
12.32
0.594
0.858
−1.195
−0.810
0.398
0.777
−0.413
−0.088
−0.996
3068973
11467554

butoconazole
9.72
2.031
1.793
0.124
−0.404
−0.267
0.908
0.378
0.515
0.017
3068976
11467556

homatropine
14.52
−0.696
−0.538
−1.372
−0.284
0.546
−0.371
−0.394
−0.753
0.358
3068999
11467210

lynestrenol
14.06
0.501
1.467
0.375
−0.592
0.575
0.855
−0.669
−0.460
−1.001
3069004
11467243

acenocoumarol
11.32
−0.433
0.530
−0.108
−0.353
1.383
−0.329
0.099
−0.004
0.254
3069006
11467258

carcinine
21.96
−0.003
0.853
−2.838
−0.375
1.637
0.716
−0.111
0.006
−0.328
3069011
11467570

metanephrine
20.28
−0.010
−0.156
−2.109
−0.722
−0.114
−0.413
−0.180
−0.322
0.095
3069040
11467270

erythromycin
5.46
0.404
0.204
0.112
0.152
−0.110
0.376
0.058
0.212
−0.314
3069044
11467299

josamycin
4.84
0.504
−0.793
−0.582
−0.902
0.157
−0.322
−0.299
−0.561
0.248
3069045
11467302

neomycin
6.22
0.823
−0.207
−0.526
−0.640
0.503
−0.498
1.110
1.006
1.055
3069046
11467306

dihydrostreptomycin
6.86
0.836
−1.306
0.190
0.027
0.243
−0.860
1.001
0.969
0.835
3069047
11467307

cyclosporine
3.32
0.145
1.037
−1.574
−0.276
0.751
−0.231
−0.739
−0.614
−0.858
3069049
11467583

carbimazole
21.48
−0.940
0.258
−0.673
0.204
0.681
0.472
−0.272
−0.322
−0.113
3069053
11467587

carbimazole
20
0.118
−0.909
−0.740
−0.239
0.121
−0.773
−0.304
−0.065
−0.670
3069053
11489067

tranylcypromine
30.04
−0.359
1.283
−1.388
−0.636
0.610
0.662
−0.967
−0.760
−1.234
3069074
11467321

aceclofenac
11.3
0.026
0.373
−1.348
−1.058
0.923
0.188
−0.732
−0.562
−0.965
3069075
11467323

tiratricol, 3,3′,5-triiodothyroacetic acid
6.44
0.899
0.450
−1.189
−0.933
2.224
0.133
−1.203
−1.019
−1.379
3069077
11467350

pyrantel tartrate
11.22
0.330
0.280
−1.214
−1.028
1.579
−0.306
−0.292
−0.094
−0.684
3069079
11467360

hydroxytacrine
19.02
−0.957
0.732
−1.910
−0.265
0.783
−0.913
−1.214
−1.177
−1.051
3069083
11467596

gamma-lumicolchicine
10.02
0.202
−0.270
−1.685
−0.866
0.216
0.280
−0.666
−0.548
−0.785
3069088
11467601

indapamide
11.44
−0.066
−0.697
−0.306
−0.256
1.075
0.210
0.864
0.591
1.227
3069113
11467368

griseofulvin
11.28
−0.976
−0.643
−1.970
−0.157
0.371
2.694
0.979
0.925
0.847
3069117
11467374

prostaglandin F2a
8.42
−0.629
−0.180
−0.518
−0.032
0.858
−0.834
−0.065
−0.110
0.041
3069122
11467608

metrizamide
5.06
0.533
−0.167
−0.578
−0.451
0.038
0.184
0.437
0.422
0.384
3069124
11467611

scopolamin-N-oxide
12.52
−0.769
0.095
−0.263
−0.602
1.578
−0.112
0.551
0.511
0.474
3069144
11467380

ceforanide
7.7
−1.144
−0.981
−0.084
0.103
0.456
−1.259
0.301
0.292
0.267
3069161
11467618

pantothenic acid
18.24
0.674
0.577
−0.424
−0.292
−0.524
0.587
0.065
0.048
0.088
3069162
11467620

vincamine
11.28
0.430
−0.634
−0.578
−1.235
0.466
0.601
−0.978
−0.922
−0.894
3069234
11467419

convolamine
13.1
−1.139
−0.271
−0.633
−0.586
0.608
0.353
−0.198
0.121
−0.799
3069519
11467744

scoulerine
12.22
0.205
−0.905
−1.969
−0.523
−0.546
−0.599
0.570
0.842
−0.080
3069520
11467749

ajmaline
12.26
0.361
−0.375
−1.763
−1.166
0.605
−0.215
−0.018
−0.022
−0.002
3069521
11467750

piperlongumine
12.6
−5.322
−8.479
−6.177
−3.952
−3.072
−4.976
−2.267
−3.189
0.033
3069522
11467752

cinchonine
13.58
−1.819
−0.404
−1.353
−0.976
1.139
−0.482
−0.336
−0.187
−0.555
3069523
11467756

chrysene-1,4-quinone
15.48
−5.351
−6.071
−3.766
−3.925
−2.891
−3.568
−1.591
−1.995
−0.459
3069524
11467763

sparteine
17.06
−0.903
−0.294
−1.355
−0.426
1.035
−0.096
−0.182
−0.071
−0.373
3069525
11467766

stachydrine
27.74
−0.162
0.242
−0.763
−0.289
0.483
0.223
−0.115
−0.139
−0.038
3069526
11467770

folic acid
9.06
−1.015
−0.238
−1.467
−0.636
−0.087
0.136
−0.215
−0.223
−0.167
3069527
11467775

retrorsine
11.38
0.133
0.249
−1.368
−0.642
0.144
−0.062
0.139
−0.111
0.612
3069528
11467785

solanine
4.6
−1.799
−0.277
−0.507
−0.194
−0.210
−0.677
−0.290
−0.450
0.110
3069529
11467788

N-acetyl-DL-homocysteine thiolactone
25.12
−0.895
1.819
−0.899
0.186
0.742
1.140
0.525
0.564
0.332
3069530
11467792

betonicine
24.98
−0.540
2.314
−1.044
0.495
1.417
1.243
0.369
0.438
0.148
3069532
11467796

halcinonide
8.8
−0.077
−0.081
−1.446
−0.172
1.375
0.020
0.738
0.740
0.592
3069534
11467803

6-furfurylaminopurine
18.58
0.152
0.370
−1.208
−0.508
0.625
0.598
0.156
0.275
−0.115
3069535
11467807

vitexin
9.26
0.412
0.151
−1.527
−0.572
1.178
0.696
−0.005
−0.067
0.098
3069536
11467809

delcorine
8.34
−0.164
−0.303
−1.152
−0.587
0.794
0.539
−0.350
−0.184
−0.626
3069538
11467812

hippeastrine
12.68
−1.004
0.183
−2.293
−1.307
0.272
0.165
0.635
1.137
−0.496
3069539
11467823

delsoline
8.56
−1.275
0.197
−1.028
−0.561
0.652
0.315
−0.043
0.081
−0.271
3069540
11467827

austricine
15.24
0.286
0.150
−1.755
−0.335
0.945
0.253
0.007
0.009
0.000
3069541
11467829

heliotrine
12.76
−0.856
0.023
−1.575
−0.855
0.383
0.203
−0.482
−0.535
−0.292
3069542
11467832

lycorine
13.92
−3.004
−0.761
−5.005
−1.958
−2.127
−1.766
0.147
1.859
−3.343
3069543
11467834

ungerine
12.14
−0.622
−0.258
−1.642
−0.628
1.505
0.114
−0.341
−0.323
−0.310
3069544
11467837

3-alpha-hydroxy-5-beta-androstan-17-one
13.78
−1.063
0.314
−1.534
−1.010
1.400
0.285
0.078
0.502
−0.786
3069570
11467845

finasteride
10.74
−1.294
0.938
−1.123
−1.106
1.464
0.352
0.005
0.035
−0.043
3069574
11467865

hecogenin
9.28
1.171
0.661
−0.341
−0.048
−0.406
−0.480
−0.354
−0.368
−0.262
3069577
11467878

nadide
6.02
0.517
0.796
−1.254
−0.741
0.435
0.922
−0.630
−0.545
−0.688
3069579
11467889

glycopyrrolate
12.56
0.316
0.546
−1.267
−0.600
−0.012
0.260
−0.876
−0.881
−0.703
3069580
11467894

cefamandole
8.64
−0.386
0.568
−0.841
−0.849
0.954
0.572
−0.695
−0.355
−1.250
3069581
11467895

mevalonic-DL-acid lactone
30.74
−0.251
0.302
−1.044
−0.183
0.874
−0.252
−0.456
−0.483
−0.317
3069582
11467898

furaltadone
12.34
−1.079
−0.861
−1.752
−0.722
0.306
0.213
−0.721
−0.631
−0.766
3069584
11467912

norgestrel
12.8
0.768
0.277
−1.551
−0.762
0.452
0.416
−0.446
−0.533
−0.192
3069624
11467921

clobetasol
8.56
−0.047
−1.143
0.131
0.360
−0.090
0.025
0.670
0.396
1.103
3069627
11467929

methazolamide
16.92
1.656
1.942
−1.025
0.011
0.229
0.663
−0.019
0.115
−0.316
3069629
11467950

methazolamide
20
−0.127
0.831
−1.451
−0.345
0.064
1.267
−0.686
−0.545
−0.852
3069629
11489359

amiprilose
13.1
−0.912
−0.145
−1.655
−0.638
0.071
0.015
−0.486
−0.407
−0.550
3069693
11467993

rolitetracycline
7.58
−1.412
0.053
−1.083
−0.670
0.192
−0.056
−0.689
−0.716
−0.496
3069696
11467997

(+)-levobunolol
13.72
0.104
0.501
−1.675
−0.908
1.585
0.040
−0.941
−0.728
−1.186
3069698
11468005

5-L-methylhydantoin
35.06
−0.181
0.072
−0.665
−0.661
0.689
−0.258
−0.094
−0.033
−0.196
3069699
11468008

5-D-methylhydantoin
35.06
−0.715
−0.277
−1.421
−1.018
1.190
0.225
−0.685
−0.586
−0.763
3069700
11468012

iopamidol
5.14
−0.303
0.059
−0.538
−0.213
0.029
0.503
0.149
0.000
0.425
3069701
11468019

diloxanide furoate
12.18
−0.260
0.233
−0.622
0.686
0.417
0.122
−0.539
−0.468
−0.588
3069737
11468051

(+)-isoproterenol
11.06
0.097
0.441
−0.943
−0.800
−0.379
0.420
−0.104
−0.256
0.228
3069738
11468059

(−)-MK 801
18.08
−1.101
0.842
−0.480
−0.786
0.889
−0.160
−0.241
−0.373
0.069
3069740
11468083

dehydroisoandosterone 3-acetate
12.1
−0.547
−0.578
0.116
−0.244
−0.010
−0.301
0.339
0.256
0.426
3069741
11468085

florfenicol
11.16
−0.049
0.713
0.263
−0.753
0.922
−0.264
1.435
0.522
3.009
3069742
11468103

deoxycorticosterone
12.1
−0.252
−0.753
−0.088
−0.274
0.606
−0.457
0.547
0.244
1.057
3069771
11468105

reserpinic acid
9.98
−0.288
0.045
−0.660
−0.289
1.085
0.975
0.329
0.302
0.313
3069774
11468132

beta-sitosterol
9.64
−0.914
0.405
−0.874
−0.600
1.323
0.231
0.161
0.153
0.138
3069775
11468133

harpagoside
8.08
−0.166
0.841
0.109
0.652
1.731
−1.270
−0.257
−0.311
−0.108
3069776
11468136

betulin
9.04
−0.544
−0.470
−0.058
0.806
0.085
0.044
1.205
1.094
1.194
3069777
11468138

pizotifen
9.32
0.473
0.797
−0.447
−0.455
0.707
0.085
0.189
0.243
0.025
3069778
11468140

cefalonium
8.7
−1.015
−0.174
−0.231
−0.323
1.280
0.133
0.445
0.366
0.505
3069779
11468144

zuclopenthixol
9.98
−0.709
−0.654
0.634
0.549
0.770
0.195
−0.953
−1.065
−0.558
3069780
11468146

alfadolone
10.24
0.943
0.045
−0.692
0.010
0.165
0.237
1.053
0.938
1.068
3069781
11468149

epitiostanol
13.06
−0.581
1.397
0.048
−0.428
0.546
0.359
0.323
0.423
0.049
3069782
11468154

etofenamate
10.84
−0.983
−0.728
−0.523
−0.727
1.003
−0.030
0.035
−0.126
0.343
3069806
11468162

isometheptene
11.38
−0.117
−0.517
−0.666
−0.648
0.842
−0.285
0.520
0.158
1.154
3069807
11468171

articaine
14.06
−0.810
−0.193
−0.378
−0.606
0.151
−0.079
0.362
0.297
0.403
3069809
11468180

methyldopate
16.72
−0.770
−0.047
−0.084
−1.190
0.669
−0.393
1.225
0.818
1.820
3069810
11468186

levocabastine
9.52
−0.450
−0.773
0.193
0.002
0.662
−0.168
1.274
0.986
1.613
3069811
11468187

etomidate
16.38
0.764
0.978
−0.504
−0.091
−1.259
1.112
−0.453
−0.436
−0.417
3069812
11468189

sertaconazole
9.14
−0.035
0.094
−0.154
1.817
−0.641
0.441
−0.590
−0.300
−1.083
3069813
11468193

quinethazone
13.8
1.510
−0.153
0.508
0.716
−0.725
−0.649
−0.313
−0.263
−0.367
3069814
11468198

trifluridine
13.5
0.052
0.174
−0.816
−1.232
0.119
0.151
−1.701
−1.587
−1.618
3069815
11468204

propoxycaine
13.58
0.868
−0.056
0.039
−0.150
0.295
−0.699
−0.235
−0.114
−0.444
3069816
11468207

naftifine
13.92
0.278
0.226
−0.084
−0.395
0.991
0.645
−0.742
−0.568
−0.970
3069817
11468211

imidurea
10.3
0.297
0.164
0.181
−0.125
−0.256
0.667
−0.061
−0.111
0.035
3069853
11468219

2-chloropyrazine
34.92
−0.139
−0.153
−0.798
−0.280
−0.218
−0.257
−0.258
−0.482
0.245
3069855
11468235

(−)-adenosine 3′,5′-cyclic monophosphate
12.16
0.242
0.438
−0.410
−0.235
0.098
0.005
−0.499
−0.260
−0.902
3069858
11468240

ramipril
9.6
0.302
−0.010
−0.370
−0.259
0.586
0.625
0.421
0.319
0.546
3069861
11468255

parbendazole
16.18
0.211
−1.119
−1.477
0.418
−1.879
−2.234
1.379
1.344
1.181
3069862
11468258

saquinavir
5.96
0.611
−0.601
0.686
0.592
−0.447
−0.484
0.787
0.752
0.692
3069863
11468262

silybin
20
0.319
0.512
−1.445
−2.599
0.594
0.150
−0.560
−0.811
0.093
3076175
11489510

geneticin
20
0.063
0.069
−1.566
−1.021
0.490
0.702
−0.980
−0.878
−1.047
3077146
11487848

secnidazole
20
−0.544
−0.336
−0.692
−0.644
0.062
0.347
−0.161
−0.213
−0.068
3077147
11487849

valeryl salycilate
20
0.248
−0.528
0.039
−0.125
1.754
0.323
0.014
−0.418
0.834
3077148
11487976

2,3-dihydroxy-4-methoxy-4′-
20
−1.074
−0.506
−1.977
−0.234
0.542
−0.089
−1.228
−1.322
−0.835
3077173
11488106

ethoxybenzophenone

apigenin
20
0.805
−0.036
−0.257
−1.267
0.836
0.721
0.040
−0.042
0.144
3077174
11488107

sappanone A 7-methyl ether
20
−0.105
−1.089
−2.259
−0.358
−1.493
−1.126
1.427
1.337
1.267
3077175
11488108

koparin
20
−0.432
0.138
−0.805
−2.598
0.782
0.261
−1.520
−1.335
−1.652
3077176
11488115

avocadynone
20
−0.153
−1.034
−0.381
−0.221
0.712
−0.441
0.381
0.071
0.867
3077177
11488116

agelasine
20
−0.071
−1.101
−0.493
−0.534
1.060
0.411
0.091
0.225
−0.257
3077178
11488125

methyl everninic acid
20
−1.028
2.351
−0.529
0.643
0.181
0.429
−0.325
−0.291
−0.297
3077346
11488220

4′-demethylepipodophyllotoxin
20
−0.436
0.522
−2.699
−0.756
−1.107
−1.030
1.666
1.806
1.098
3077356
11488261

avocadene
20
−0.025
0.936
−0.545
−0.147
0.967
−0.088
0.385
0.303
0.448
3078269
11488534

zolmitriptan
20
−0.161
1.349
−0.543
0.585
1.164
0.806
1.249
1.604
0.283
3078270
11488544

3alpha-hydroxy-3-deoxyangolensic acid methyl
20
1.034
1.264
−0.370
0.251
1.295
−1.732
−0.196
−0.177
−0.212
3078271
11488564

ester

mesna
20
−0.680
0.889
−1.600
−0.699
0.932
0.598
−0.900
−0.827
−0.887
3078272
11488568

baeomycesic acid
20
−0.434
0.400
−0.619
−1.694
0.844
0.171
0.192
0.350
−0.188
3078273
11488609

L-phenylalaninol
20
−0.379
0.911
−0.205
−0.043
1.158
−0.858
−0.124
−0.071
−0.233
3078274
11488646

I-alaninol
20
−0.353
0.737
−0.342
−0.428
0.242
0.301
−0.652
−0.555
−0.738
3078275
11488647

carbadox
20
−0.905
−0.297
−1.334
−1.394
−0.079
−0.250
−0.802
−0.599
−1.076
3078276
11488649

apramycin
20
−1.979
1.018
−0.808
−0.407
−0.105
0.223
0.477
0.413
0.494
3078277
11488650

5-fluoro-5′-deoxyuridine
20
0.242
0.603
−2.176
−0.828
0.337
0.338
−0.336
−0.284
−0.387
3078281
11488713

pyrocatechuic acid
20
−1.076
1.015
−1.800
−1.204
1.147
−0.018
−0.386
−0.324
−0.367
3078331
11488902

bisabolol
20
0.300
0.982
0.031
−0.234
0.061
0.738
−0.963
−0.983
−0.690
3078456
11488307

sertraline
20
0.279
−1.302
−1.905
0.420
0.090
−1.121
−1.068
−1.476
0.020
3078457
11488309

ginkgolic acid
20
−0.686
0.489
−0.461
−0.905
−0.116
0.587
−0.062
−0.315
0.505
3078458
11488330

alverine citrate
20
0.885
−2.140
−0.018
0.433
1.116
−0.433
−0.238
−0.098
−0.442
3078459
11488396

cefditorin pivoxil
20
−0.219
1.534
−0.718
0.245
0.426
0.200
0.238
0.100
0.440
3078460
11488463

4-aminoethylbenzenesulfonyl fluoride
20
−0.304
1.073
−1.406
−0.356
1.081
−0.485
−0.016
−0.045
0.018
3078461
11488474

sodium fluoroacetate
20
−0.906
0.006
−1.379
−0.784
0.613
0.653
−0.009
0.206
−0.459
3078462
11488480

ethyl everninate
20
−1.061
0.492
−1.302
−0.860
0.125
0.122
−0.428
−0.131
−0.980
3078463
11488500

7-oxocallitrisic acid, methyl ester
20
1.266
−0.302
0.111
2.079
0.162
−0.923
−0.876
−0.457
−1.555
3079211
11489276

cadaverine
20
−1.003
0.066
−0.915
−0.730
0.160
−0.135
−0.553
−0.667
−0.205
3079212
11489303

S-(1,2-dicarboxyethyl)glutathione
20
−0.049
−0.160
−0.635
0.038
0.258
−0.411
−0.364
−0.400
−0.219
3079213
11489306

glycylleucylphenylalanine
20
−0.254
0.418
−0.344
−0.774
0.973
−0.182
−0.095
0.033
−0.322
3079214
11489311

L-leucyl-L-alanine
20
−0.600
0.475
−0.320
−0.307
0.301
−0.861
0.365
0.465
0.093
3079215
11489315

cosmosiin
20
0.141
−0.890
−0.801
0.053
−0.052
−0.009
−0.433
−0.287
−0.611
3079222
11489447

mercaptamine
20
−0.271
0.601
−0.085
−0.724
−0.661
0.320
−1.175
−0.980
−1.294
3079223
11489483

rhodocladonic acid
20
−0.416
1.670
−1.057
0.068
0.733
1.150
0.294
0.393
0.072
3079224
11489503

lupanyl acid
20
−0.245
0.049
−0.734
0.351
0.610
0.451
0.585
0.578
0.507
3079225
11489504

desoxypeganine
20
−0.281
0.956
1.441
1.046
0.647
0.372
0.631
0.621
0.556
3079226
11489506

imidacloprid
20
−0.121
−0.094
−0.893
−0.019
0.075
0.607
−0.294
−0.214
−0.368
3079227
11489508

theanine
20
−0.613
0.157
−0.851
−0.557
0.615
0.244
−1.153
−1.209
−0.778
3079228
11489509

3,4-dihydroxycarane
20
0.448
−0.280
−0.697
−0.659
0.697
0.475
−1.265
−0.951
−1.620
3079229
11489517

limonin
20
−0.818
−0.078
−1.564
−0.668
1.165
0.042
−0.197
−0.317
0.127
3079231
11489544

7-methoxychromone
20
−0.999
−0.063
−0.963
−0.875
0.919
0.511
−0.759
−0.818
−0.451
3079232
11489563

methyl orsellinate
20
−0.008
0.487
0.148
−0.632
1.212
0.573
−1.129
−1.000
−1.146
3079279
11489567

(2R,3R)-(−)-epiafzelechin
20
−0.719
0.986
−0.486
−3.118
1.019
0.166
−0.497
−0.559
−0.225
3079280
11489571

anhydroglucose
20
0.168
0.059
0.041
−0.480
0.238
0.688
−0.046
0.322
−0.745
3079366
11489627

amitraz
20
−1.025
0.305
−1.572
−0.741
0.867
0.292
−0.526
−0.299
−0.814
3079387
11489059

12-methoxy-4,4-bisnor-5alpha-8,11,13-
20
−1.078
0.068
−2.017
−0.840
0.559
−0.087
−0.375
−0.350
−0.270
3079388
11489071

podocarpatrien-3-ol

iriflophenone trimethyl ether
20
0.717
−0.605
−0.380
0.248
−0.015
0.032
−1.156
−1.252
−0.696
3079389
11489651

dihydrorobustic acid
20
−0.721
2.345
−0.780
0.000
−0.115
0.757
−0.836
−0.849
−0.701
3080393
11489739

2-methyl-5,7,8-trimethoxyisoflavone
20
−0.656
1.653
−0.531
0.306
−0.371
1.063
0.495
0.629
0.081
3080394
11489743

cholestane
20
0.941
0.220
−1.057
−0.945
0.155
0.043
−0.678
−0.651
−0.640
3080395
11489777

diprotin B
20
−0.639
0.330
−0.589
0.153
0.689
−1.537
−0.522
−0.682
−0.126
3080396
11489806

benzamil
12.5
0.375
0.682
−1.629
−1.018
0.723
0.865
−0.204
−0.071
−0.434
3103678
11467805

parthenolide
16.1
−4.944
−7.991
−6.260
−3.801
−1.572
−4.930
−0.072
−0.221
0.260
3103826
11467698

protoveratrine B
20
0.708
0.029
0.904
0.942
0.244
−1.085
0.018
0.058
−0.096
3172708
11488626

cefotaxime
20
−1.283
0.479
−2.276
−0.276
1.000
0.366
−0.379
−0.450
−0.214
3172713
11487935

pralidoxime
29.16
0.060
0.594
−0.520
0.056
−0.098
0.914
0.502
0.438
0.523
3172714
11468091

pralidoxime
20
−1.011
0.365
−0.372
−0.513
−0.152
0.329
−1.793
−1.380
−2.309
3172714
11488737

nitrofural
20.18
0.584
1.443
−0.852
−0.518
0.446
0.342
−0.260
−0.010
−0.750
3172716
11467640

nitrofurazone
20
0.544
1.199
−0.617
−0.185
2.173
0.785
−0.199
0.038
−0.643
3172716
11488473

gentamicin sulfate
20
−0.804
−0.234
−0.150
−1.213
0.369
−0.896
−0.117
−0.267
0.188
3172720
11488504

cafestol
20
0.025
0.332
1.124
1.283
0.832
1.374
−0.833
−0.385
−1.543
3172723
11489427

cantharidin
20.38
−4.714
−6.628
−5.122
−2.722
−2.786
−5.104
0.217
0.144
0.310
3172726
11468033

cantharidin
20
−4.063
−6.195
−5.729
−2.513
−2.764
−5.284
1.196
0.477
2.498
3172726
11488446

betulin
20
−0.184
0.187
−1.669
−0.008
0.633
0.150
0.570
0.598
0.442
3172727
11488436

methomyl
20
1.361
−0.211
−1.481
−0.493
0.231
−0.007
−0.703
−0.805
−0.317
3172728
11489688

kinetin riboside
20
−1.883
−2.070
−4.309
−1.350
−2.722
−2.612
0.882
0.853
0.750
3172730
11489269

clarithromycin
20
−0.763
−0.911
−1.086
0.434
0.293
−1.095
−2.161
−2.046
−1.928
3172732
11489484

carminic acid
20
−0.905
−0.059
−1.295
−0.378
0.083
−0.243
−0.727
−0.662
−0.671
3172733
11488426

protoveratrine A
20
0.243
1.266
−0.100
0.394
−0.267
1.155
−1.106
−0.978
−1.108
3172845
11488377

ketorolac
10.62
−0.773
−0.629
−0.563
0.136
0.482
0.315
0.096
−0.072
0.412
3172846
11468077

ketorolac
20
−0.363
−0.259
−0.053
−0.825
0.939
−0.707
−0.344
−0.468
−0.033
3172846
11489414

nicotine
20
−0.093
0.808
−1.228
−0.423
0.503
0.348
−1.360
−1.032
−1.705
3172849
11489029

dexamethasone acetate
20
−1.518
0.307
0.058
−0.439
0.067
0.174
0.461
0.516
0.330
3172851
11488847

hederagenin
20
0.310
0.064
−1.259
−0.901
0.385
0.945
−0.654
−0.630
−0.540
3172852
11489437

sapindoside A
20
−3.886
−4.232
−4.558
−3.760
−2.825
−4.058
−1.176
−1.786
0.322
3172853
11489438

lycorine
20
−2.922
0.198
−4.612
−2.570
−2.639
−1.288
−1.119
1.103
−5.387
3172856
11488234

cytisine
20
−0.076
0.069
0.571
−0.397
1.150
0.186
0.025
0.027
0.052
3172862
11488286

cyclosporine
20
0.161
0.951
−0.887
−0.126
0.791
−0.632
−0.627
−0.631
−0.496
3172968
11489300

azadirachtin
20
−0.479
0.299
−1.018
−0.670
0.494
−0.421
0.119
0.152
0.042
3172973
11489402

ouabain
20
−0.631
0.320
−2.101
−1.093
0.466
0.262
−1.278
−0.986
−1.547
3172974
11488900

diosgenin
20
−0.044
−0.057
−1.597
−0.353
0.048
−0.679
−0.245
−0.445
0.146
3172979
11488034

pristimerin
20
−5.473
−8.234
−6.164
−3.651
−3.693
−5.896
ND
ND
ND
3172984
11488362

hetacillin
20
−0.642
1.231
−0.663
−0.787
1.132
0.731
−0.200
−0.094
−0.302
3173079
11488932

metoprolol
9.58
0.437
0.449
−1.894
−0.997
0.253
0.496
−0.423
−0.430
−0.342
3173081
11467881

metoprolol
20
0.326
1.130
−1.660
−0.515
0.652
0.596
0.450
0.546
0.241
3173081
11488873

spiramycin
20
0.176
0.288
−0.770
−0.686
0.379
0.216
−0.691
−0.867
−0.204
3173083
11489377

neomycin
20
−1.255
−1.028
−1.478
−0.599
1.203
0.734
0.817
0.598
1.160
3173091
11488285

dimenhydrinate
20
−1.060
−0.597
−1.505
−0.890
0.339
0.251
−0.225
−0.086
−0.390
3173092
11488808

leoidin
20
0.035
−0.082
0.994
−1.352
1.481
0.341
−0.611
−0.523
−0.638
3173106
11488437

tomatidine
20
0.490
0.445
−1.376
−0.425
1.323
0.913
−1.375
−1.473
−0.857
3173115
11488248

ceftriaxone
20
−0.792
−0.735
−1.040
−0.461
−0.002
0.481
−0.433
−0.439
−0.382
3173210
11487838

puromycin
20
−5.718
−7.962
−5.624
−3.989
−2.665
−5.573
−3.348
−4.017
−1.331
3173213
11488712

oxacillin sodium
20
−1.101
−0.038
−1.064
−0.432
0.572
−0.361
−0.790
−0.629
−0.881
3173215
11488844

aconitine
20
0.132
0.350
−0.584
−0.073
1.038
0.751
0.169
0.356
−0.198
3173217
11488453

3-methylxanthine
20
0.036
0.704
−0.859
−0.149
0.472
0.692
−1.241
−1.286
−0.856
3173234
11488318

pinacidil
16.3
−0.477
0.891
−0.889
−0.614
0.383
0.027
−0.146
0.038
−0.498
3173239
11467394

pinacidil
20
−0.062
−0.566
−0.142
−0.949
0.655
1.030
−0.515
−0.301
−0.814
3173239
11489555

androsterone
20
−0.882
0.711
−0.685
−0.846
0.619
−0.302
−0.061
−0.099
0.009
3173241
11488748

zoxazolamine
23.72
−0.415
1.480
−0.303
−0.068
1.630
0.552
0.447
0.517
0.203
3173242
11467476

zoxazolamine
20
−0.121
−0.099
−0.667
−0.780
0.657
1.131
−0.531
−0.242
−1.036
3173242
11488587

cefuroxime
20
−0.846
0.476
−0.536
−0.358
0.366
−0.495
0.816
0.790
0.699
3173342
11488522

lasalocid
20
−1.090
−0.906
−1.771
−1.178
−2.993
−1.690
−1.524
0.274
−4.908
3173346
11488680

deoxygedunin
20
−0.326
1.094
−0.532
1.327
−0.640
1.083
−1.229
−1.298
−0.808
3173352
11488148

betulinic acid
20
0.850
−0.271
−2.381
−1.220
0.202
0.481
0.145
0.069
0.259
3173357
11488632

ursocholanic acid
20
0.050
0.349
−0.246
−1.738
0.978
1.303
−0.920
−0.946
−0.657
3173360
11488440

tomatine
20
−4.793
−5.117
−4.122
−2.423
−2.084
−3.979
−2.151
−2.158
−1.725
3173364
11488756

lunarine
20
−0.579
0.517
−0.938
−0.795
0.385
0.685
−0.945
−0.880
−0.856
3173368
11488159

totarol acetate
20
−0.273
0.031
0.730
−0.556
0.452
1.207
0.574
0.830
−0.125
3173369
11488083

isoxsuprine
20
−0.141
−0.160
−1.776
−1.246
1.375
0.295
−0.050
−0.267
0.463
3173462
11488881

nitrofurantoin
16.8
0.779
−0.264
−0.586
0.358
−0.261
0.122
−0.224
−0.031
−0.618
3173466
11467316

nitrofurantoin
20
0.233
0.261
−1.489
0.956
0.728
1.050
0.224
0.250
0.202
3173466
11488862

quinidine
20
0.916
0.901
−0.233
1.187
1.326
1.286
0.849
0.956
0.501
3173468
11488224

estradiol
20
0.400
0.137
−1.040
−0.085
0.310
0.389
0.290
0.410
−0.058
3173471
11487879

troleandomycin
20
−1.520
0.194
−1.250
−0.780
0.099
−0.063
−1.234
−1.277
−0.905
3173475
11489301

friedelin
20
0.082
0.462
−1.362
−0.867
0.449
0.614
−1.043
−1.150
−0.600
3173478
11488168

sennoside A
20
0.602
−0.358
−0.769
−0.640
0.137
0.362
−1.374
−1.093
−1.628
3173485
11489458

colchiceine
20
−0.333
−0.848
−3.186
−0.812
0.469
−0.908
1.832
1.935
1.192
3173492
11488112

formestane
20
−0.582
−0.830
−0.725
−0.608
1.013
−0.115
0.097
0.050
0.121
3173493
11487845

pyrantel pamoate
20
−1.934
−0.426
−0.189
−2.829
0.592
0.640
−0.468
−0.500
−0.327
3173593
11489120

nystatin
20
0.794
0.843
0.161
−0.356
−0.043
−0.059
0.326
0.284
0.289
3173595
11487887

naloxone
20
0.399
2.752
−0.667
0.353
0.782
0.362
0.316
0.420
0.107
3173600
11488865

gitoxigenin diacetate
20
0.187
1.895
−1.077
−0.792
0.508
0.684
−0.594
−0.649
−0.322
3173612
11488177

beta-sitosterol
20
−0.768
−0.419
−1.974
−0.679
0.049
0.061
0.098
0.046
0.218
3173615
11488194

deoxyguanosine
20
−0.819
0.734
−0.703
−0.268
−0.110
0.695
−0.001
−0.090
0.245
3173625
11488960

ergosterol acetate
20
0.023
1.578
−1.580
0.050
0.270
0.346
−0.380
−0.220
−0.680
3173626
11489745

pempidine
13.1
−1.023
0.278
−2.128
−0.967
1.119
0.163
−0.656
−0.425
−0.998
3173628
11467831

pempidine
20
−0.822
0.192
−1.419
−0.376
0.861
0.146
−0.874
−1.035
−0.378
3173628
11489371

cephalexin
20
0.343
0.201
−0.506
−0.353
−0.316
0.678
−0.957
−0.950
−0.783
3173633
11489277

amikacin
20
0.034
−0.527
−1.688
−0.116
0.301
−0.090
0.332
0.268
0.338
3173722
11487918

piperacillin
20
−0.990
0.634
−1.188
−0.150
0.645
0.544
−0.548
−0.339
−0.857
3173725
11489102

pasiniazid
20
−0.883
1.328
−0.807
−0.809
0.502
0.590
−0.059
−0.022
−0.164
3173726
11489752

dihydrorotenone
20
0.390
−5.350
−4.020
−0.314
−0.682
−3.153
−2.179
−2.212
−1.732
3173749
11487997

cortisone
20
0.644
0.319
−0.146
−0.232
0.527
−0.078
−0.428
−0.165
−0.830
3173755
11489640

etoposide
20
−1.541
0.749
−2.352
0.050
−1.736
−0.491
0.725
0.355
1.373
3173759
11488278

berbamine
20
−1.126
0.168
−1.021
−0.289
0.153
0.445
−0.345
−0.166
−0.636
3173760
11489211

cefaclor
10.88
0.762
0.678
−1.329
−0.759
0.387
−0.764
0.331
0.535
−0.161
3173761
11467633

loracarbef
10.88
0.317
−0.098
−0.158
−0.229
−0.236
0.622
0.129
0.215
−0.088
3173761
11468250

cefaclor
20
−0.091
0.137
−0.752
−0.772
0.297
0.231
−0.547
−0.506
−0.435
3173761
11489005

amphotericin B
20
−0.453
0.979
−1.466
−0.292
0.428
−0.174
−0.423
−0.355
−0.499
3173762
11488634

chlorogenic acid
11.28
−0.739
0.607
−0.944
−0.943
0.188
0.039
0.096
0.348
−0.436
3173763
11467575

chlorogenic acid
20
−0.720
0.442
−1.629
−0.960
−0.173
0.279
−0.263
−0.374
0.044
3173763
11489714

neohesperidin dihydrochalcone
20
0.061
2.411
−0.964
0.231
0.934
0.454
−0.190
−0.372
0.259
3173852
11488144

roxithromycin
20
0.513
0.595
−1.163
−0.352
1.120
0.218
−1.024
−0.962
−0.958
3173855
11489367

atractyloside
5.5
−0.186
1.229
−0.683
−0.663
1.160
0.174
−0.311
−0.117
−0.644
3173859
11467885

atractyloside
20
−1.047
−0.662
−1.079
−1.061
1.313
0.233
0.161
0.350
−0.182
3173859
11488914

nalbuphine
20
−1.422
0.390
−1.511
−0.919
0.042
0.276
−0.210
−0.124
−0.342
3173860
11489219

mexicanolide
20
0.816
1.008
0.311
−0.046
0.479
−0.406
0.457
0.204
0.819
3173867
11488056

sericetin diacetate
20
0.051
0.104
−1.876
2.433
0.923
0.565
−0.479
−0.257
−0.892
3173879
11487994

bacampicillin
20
1.335
1.827
−0.488
0.062
−0.192
0.127
−1.269
−1.161
−1.241
3173981
11489339

gitoxigenin
20
−0.731
1.363
−1.879
−0.540
1.427
0.100
−0.281
−0.465
0.081
3173991
11488104

totarol
20
−0.254
−0.267
2.622
−0.623
0.932
0.561
−0.724
−0.384
−1.324
3173992
11488087

yohimbinic acid
11.76
−0.378
−0.041
−0.978
−0.282
0.723
0.509
0.280
0.670
−0.554
3173993
11467738

yohimbic acid
20
−0.310
0.412
−1.098
−0.825
0.706
−0.364
−0.564
−0.534
−0.479
3173993
11488267

digitonin
20
−2.207
−1.486
−3.750
0.139
−0.404
−1.798
0.135
0.392
−0.476
3173995
11488094

andirobin
20
0.649
2.119
−0.285
−0.261
0.082
0.496
−0.225
−0.230
−0.218
3173997
11488040

grayanotoxin I
20
0.289
−0.096
0.059
−0.414
−0.171
0.127
0.729
0.652
0.807
3173998
11488373

hecogenin acetate
20
−0.683
0.317
−1.994
−0.849
1.816
−0.050
−0.434
−0.610
−0.030
3173999
11488092

smilagenin
20
−0.808
0.483
−0.266
−1.153
0.310
0.178
0.310
0.289
0.354
3174000
11488193

pararosaniline
20
−1.866
−6.271
−4.910
−3.740
−2.532
−2.574
−3.501
−2.247
−5.433
3174099
11487823

mebhydrolin
7.08
−0.133
−0.958
−1.229
−0.707
0.498
−0.530
−0.637
−0.506
−0.778
3174101
11467603

mebhydrolin
20
−1.749
−0.854
−0.416
−0.755
0.225
−0.059
−1.338
−1.268
−1.242
3174101
11488496

hydroxyzine
20
−0.625
0.258
−0.494
−0.800
1.424
−0.524
−0.625
−0.468
−0.748
3174102
11488816

parthenolide
20
−5.215
−7.573
−6.275
−3.817
−0.693
−4.905
−4.012
−4.775
−1.601
3174103
11489036

pyrvinium pamoate
20
−2.225
−5.052
−4.560
−2.938
−1.987
−1.309
−3.051
−2.082
−4.397
3174105
11489123

amiprilose
20
0.222
0.110
0.819
0.027
0.174
−0.501
0.441
0.317
0.622
3174106
11489335

sisomicin
20
−1.118
0.313
−1.365
−0.820
0.032
0.158
−0.360
−0.407
−0.193
3174107
11489130

fucostanol
20
−1.432
−0.453
−3.092
−0.990
−0.122
0.205
−0.411
−0.385
−0.339
3174115
11489450

roccellic acid
20
0.383
1.062
−1.673
−0.462
0.175
0.909
−0.208
−0.128
−0.308
3174120
11488388

nigericin
20
−1.744
−3.165
−3.329
1.324
−3.323
−2.497
−2.367
−1.736
−3.122
3174220
11488991

bretylium
20
−0.775
−0.361
−0.446
−1.114
0.632
0.560
0.996
1.057
0.732
3174226
11488289

ajmaline
20
−0.003
0.454
0.064
−0.147
1.176
0.191
0.979
0.728
1.229
3174227
11487896

dihydrostreptomycin
20
0.042
0.519
−0.944
−0.650
0.203
0.491
−0.421
−0.329
−0.454
3174228
11488818

theaflavin
20
−0.618
0.975
−0.396
−0.825
−0.159
0.599
−0.373
−0.328
−0.366
3174236
11489581

arbutin
20
−0.752
0.483
−0.695
−0.536
0.188
0.067
0.044
0.163
−0.219
3174242
11488478

leucopterin
20
−0.307
−0.202
−2.409
−0.179
1.106
0.494
0.752
0.995
0.150
3174244
11488403

phloridzin
20
0.317
0.210
−0.331
−0.473
−0.176
0.286
0.052
−0.036
0.209
3174245
11488517

deoxycholic acid
20
−0.892
0.037
−1.242
−1.081
0.761
0.185
−0.302
−0.333
−0.139
3174249
11488172

meclocycline
5.76
−0.275
0.410
−1.589
−1.670
−0.005
−0.222
−0.126
−0.412
0.481
3174345
11467604

meclocycline
20
−0.581
0.172
−1.677
−1.519
0.162
0.012
0.381
−0.142
1.368
3174345
11489221

smilagenin acetate
20
−0.607
−0.117
−1.356
−0.152
0.585
0.611
−1.252
−1.258
−1.047
3174366
11488089

carnosine
20
−0.898
−0.025
−1.714
−1.120
0.886
0.073
−0.626
−0.572
−0.578
3174367
11488270

gitoxin
20
0.002
1.035
−0.671
−0.627
1.680
0.826
0.380
0.391
0.277
3174369
11489192

vancomycin
20
−0.443
−0.409
−0.759
−0.160
1.370
0.092
0.176
−0.291
1.039
3174477
11487885

adrenaline
20
−0.736
−0.317
−1.299
−1.202
0.190
0.173
0.000
0.076
−0.076
3174481
11488809

epiandrosterone
20
−0.177
−0.525
1.264
0.291
0.791
0.256
−0.340
−0.569
0.240
3174484
11489724

scopoline
20
0.047
0.688
−0.511
−0.807
0.233
0.179
−1.331
−0.982
−1.815
3174492
11488498

glucosaminic acid
20
−0.238
−0.832
0.276
−0.814
0.607
−0.516
0.053
0.080
0.030
3174493
11489726

hypoxanthine
20
−0.202
−0.570
−0.965
−2.156
1.178
0.608
−1.781
0.575
−6.147
3174602
11489723

quebrachitol
20
−1.126
−0.067
−1.017
−0.561
0.361
−0.256
−0.508
−0.525
−0.402
3174608
11489804

atorvastatin
20
0.043
−0.945
−1.529
−0.744
−0.940
−1.023
0.764
0.618
0.924
3174609
11489401

veratridine
20
0.161
0.642
−0.084
−0.453
0.719
0.294
0.021
0.203
−0.352
3174610
11489397

cholest-5-en-3-one
20
0.207
1.026
−0.937
−0.686
0.629
0.600
0.959
0.943
0.850
3174615
11488452

D-cycloserine
39.18
−0.586
0.002
−0.453
−0.166
0.042
−0.620
0.242
0.146
0.384
3176921
11468234

cortisone
11.1
−0.705
0.407
−1.467
−0.740
0.184
0.063
0.059
0.177
−0.184
3176928
11467421

cefsulodin
7.5
0.117
0.384
−2.002
−0.652
0.951
0.836
−0.492
−0.377
−0.637
3176931
11467962

1-benzyloxycarbonylaminophenethyl
20
−5.468
−8.086
−6.339
−4.136
−4.285
−5.377
−3.760
−4.030
−2.480
3176939
11489309

fluvoxamine
12.56
−0.521
−0.252
−0.012
−0.258
0.826
0.483
0.445
0.590
0.052
3177109
11468143

famotidine
11.86
−0.118
1.643
−1.496
−0.409
−0.094
0.528
−0.974
−0.963
−0.847
3177110
11467252

ifenprodil
8.42
0.882
1.184
0.999
0.021
2.016
0.674
−0.614
−0.356
−1.023
3177204
11467459

metergoline
9.92
0.243
−1.286
−2.643
0.173
0.787
−1.385
−0.572
−0.652
−0.294
3177235
11467512

betamethasone
20
0.284
−0.954
−0.977
0.629
0.940
−0.109
1.063
0.780
1.370
3177311
11487916

lathosterol
20
0.543
0.872
0.907
−0.333
0.526
0.513
−0.655
−0.691
−0.410
3177312
11488390

garcinolic acid
20
−1.005
0.053
−1.674
−2.471
0.651
−0.290
−0.570
−0.474
−0.615
3177314
11488423

quercitrin
20
0.140
1.903
−0.628
−1.249
−0.769
0.555
−0.402
−0.644
0.216
3177315
11488145

convallatoxin
20
−0.832
0.676
−1.168
−0.507
0.948
−0.282
−0.371
−0.285
−0.392
3177316
11489055

hydroxyprogesterone
20
0.895
0.883
−0.258
−0.099
0.872
0.560
−0.869
−0.820
−0.726
3177322
11489035

tetrahydrocortisone
20
−0.055
−0.693
−0.738
−0.571
0.385
0.107
−0.663
−0.806
−0.204
3177324
11489641

pancuronium
6.98
−1.055
−0.433
−1.235
−0.576
−0.179
−0.073
−0.453
−0.374
−0.543
3177327
11468182

alfaxalone
12.04
0.513
−0.004
−0.849
−0.649
0.564
0.093
0.542
0.635
0.238
3177333
11468150

larixol acetate
20
0.353
0.412
0.101
−0.432
1.144
0.494
0.325
0.062
0.728
3177379
11488134

4′-hydroxychalcone
20
−0.880
0.046
−0.477
0.065
0.829
0.147
−0.950
−0.964
−0.776
3177381
11488019

fluocinolone
20
−0.508
0.341
−1.445
1.685
0.067
−0.050
−0.823
−0.898
−0.456
3177385
11488780

kanamycin A
20
0.182
0.186
−1.330
−0.482
1.129
0.162
0.144
0.404
−0.331
3177386
11488875

noscapine
20
−0.689
0.824
−0.648
−0.510
0.430
−0.297
0.703
0.700
0.635
3177388
11488803

tobramycin
20
0.089
0.932
−1.891
−0.443
0.298
−0.107
1.081
0.956
1.057
3177389
11487894

quinidine
12.32
−0.793
−0.292
−0.681
−0.382
0.645
−1.130
0.061
0.239
−0.305
3177396
11467428

fludrocortisone acetate
20
−0.750
0.458
−1.485
−0.196
−0.743
0.274
−0.475
−0.511
−0.251
3177451
11488790

fluocinonide
20
−0.905
0.097
−0.828
−0.144
0.316
−0.368
0.073
0.220
−0.165
3177453
11488851

cholesterol
20
−0.465
1.823
−1.608
−0.480
0.973
−0.060
−1.174
−1.232
−0.783
3177456
11488400

dehydrocholic acid
20
0.134
0.643
−1.560
−0.858
0.931
0.257
0.457
0.463
0.346
3177457
11489191

estrone acetate
20
0.145
0.679
−0.536
−0.663
1.773
0.398
0.491
0.251
0.892
3177458
11489254

anisodamine
20
−0.095
0.462
−0.373
−0.288
0.202
0.466
−0.130
−0.214
0.050
3177461
11488548

betamethasone
20
−0.467
−0.131
−0.718
−0.100
0.346
−0.942
−0.113
−0.292
0.341
3177462
11489076

cephradine
20
−0.745
−0.188
−2.067
−0.807
0.177
0.431
−0.562
−0.484
−0.539
3177463
11489050

capreomycin
20
0.882
−0.979
0.181
−0.639
−0.197
0.523
−0.163
−0.284
0.071
3177464
11487877

oleandrin
20
0.691
1.192
−0.702
−1.297
0.501
0.175
−0.262
0.148
−0.979
3177465
11488989

paromomycin
20
−0.604
0.853
−0.913
−0.507
0.620
−1.032
0.573
0.546
0.508
3177517
11488675

picropodophyllotoxin acetate
20
0.072
1.141
−2.400
−0.390
−1.714
−0.889
0.731
0.716
0.601
3177521
11488623

pyrromycin
20
−3.145
−2.578
−4.056
−3.412
−2.008
−1.138
−3.027
−2.886
−2.670
3177523
11488510

nateglinide
20
−0.543
0.143
−1.183
0.146
−0.581
−0.517
−0.828
−0.933
−0.420
3177524
11489490

ornithine alphaketoglutarate
20
−1.493
0.259
−2.104
−0.917
0.840
0.085
−0.715
−0.605
−0.727
3177525
11489060

podophyllotoxin acetate
20
−0.983
−3.008
−3.102
1.238
−1.656
−0.777
1.407
1.426
1.125
3177591
11489497

vancomycin
2.76
0.012
0.458
−0.636
−0.833
0.921
0.898
−0.289
−0.139
−0.538
3177604
11467645

seneciphylline
12
−0.903
−0.239
−0.529
−0.146
0.686
−0.683
0.156
0.117
0.207
3179848
11467747

cephaeline
8.58
−5.685
−7.376
−6.133
−3.335
−2.842
−5.599
0.138
0.347
−0.334
3180147
11467576

hydrastine
10.44
0.263
0.516
−0.863
−0.212
−0.017
0.525
0.063
0.032
0.113
3180327
11467729

conessine
11.22
0.176
−0.350
−1.669
−0.471
1.082
−1.296
0.380
0.265
0.533
3187609
11467786

protoveratrine A
5.04
0.433
−0.715
0.464
−0.287
1.528
−0.449
0.253
0.083
0.556
3187610
11467787

sulmazole
13.92
−0.386
1.451
−0.531
1.306
0.713
1.129
−0.572
−0.514
−0.582
3187611
11467789

flunisolide
9.2
−0.594
2.843
−0.529
1.025
0.560
0.715
−0.106
−0.123
−0.076
3187612
11467791

helveticoside
7.48
−0.288
0.775
−1.371
0.073
0.744
0.833
0.266
0.515
−0.297
3187613
11467794

butirosin
7.2
0.351
1.806
−0.874
0.889
0.651
0.589
−0.043
−0.077
0.033
3187614
11467798

picrotoxinin
13.68
0.091
0.839
−1.834
−0.355
0.724
0.990
−0.116
0.095
−0.523
3187615
11467800

benfotiamine
8.58
−0.050
0.589
−1.356
−0.899
0.881
0.432
−0.230
−0.075
−0.505
3187616
11467802

lanatoside C
3.94
0.288
0.484
−1.387
−1.272
1.913
0.987
−0.227
−0.136
−0.358
3187617
11467804

avermectin B1
4.58
1.166
0.659
−0.348
−0.149
1.616
0.671
−0.150
−0.164
−0.090
3187618
11467808

solasodine
9.68
0.047
0.668
−1.453
−0.916
1.169
0.552
−0.666
−0.709
−0.453
3187619
11467811

cis-nanophine
35.34
−0.528
−0.212
−1.551
−0.963
1.222
0.531
−0.115
−0.009
−0.302
3187620
11467814

deltaline
7.88
−0.669
−0.108
−2.022
−0.929
1.524
0.294
0.098
0.107
0.064
3187622
11467821

beta-escin
3.54
−4.210
−2.955
−4.299
−2.682
−1.103
−3.298
−0.967
−0.781
−1.155
3187623
11467824

fluorocurarine
13.02
−0.665
0.010
−0.478
0.130
0.525
0.243
−0.014
0.119
−0.272
3187624
11467828

beta-belladonnine
6.66
−0.094
−0.245
−2.121
−0.640
1.001
0.178
−0.451
−0.292
−0.668
3187625
11467830

karakoline
10.6
−0.568
−0.087
−1.657
−1.112
1.495
0.002
−0.263
−0.087
−0.569
3187744
11467835

estropipate
11.42
−0.518
−0.300
−0.645
−1.201
1.736
0.041
−0.181
−0.270
0.039
3187745
11467836

napelline
11.12
−0.454
0.567
−0.919
−0.860
0.692
0.185
0.004
0.128
−0.243
3187746
11467838

fillalbin
13.72
−0.600
−0.022
−1.166
−0.608
1.228
0.700
−0.441
−0.163
−0.916
3187747
11467839

tadjakonine
7.5
−0.403
−0.136
−2.254
−0.450
1.190
−0.096
0.172
0.187
0.092
3187748
11467840

cefuroxime
9.42
−0.256
0.739
0.036
−0.292
0.761
0.579
−0.317
−0.397
−0.088
3187749
11467868

ergocryptine-alpha
6.94
2.729
1.621
−1.580
−0.856
0.377
1.295
0.143
0.382
−0.378
3187750
11467875

streptozosin
15.08
−0.478
0.524
−1.635
−0.996
0.393
0.701
−0.256
−0.052
−0.636
3187751
11467880

flumethasone
9.74
−1.279
−0.148
−2.146
−0.541
−0.131
0.569
−0.930
−1.042
−0.538
3187752
11467882

medrysone
11.62
−0.104
0.397
−1.658
−0.181
0.293
0.345
−0.018
0.091
−0.247
3187753
11467891

flunixin
8.14
−0.127
0.853
−1.908
−0.285
0.496
0.847
−0.300
−0.010
−0.860
3187754
11467892

spiramycin
4.74
0.003
0.427
−1.238
−0.834
1.762
0.865
−0.313
−0.476
0.061
3187755
11467893

monensin
5.96
−0.307
−3.555
−3.197
1.556
−1.933
−2.647
−0.958
0.698
−4.135
3187756
11467896

ribostamycin
8.8
−0.815
−0.466
−1.657
−0.217
−0.168
−0.664
0.029
0.313
−0.552
3187757
11467906

guanadrel
18.76
−0.871
0.589
−0.889
−0.629
2.273
−0.062
−0.912
−0.898
−0.766
3187758
11467915

alclometasone dipropionate
7.68
−0.005
−0.333
−1.105
−0.064
−0.101
−0.061
0.262
0.217
0.301
3187759
11467919

fluocinonide
8.08
−0.747
−0.851
−2.438
−0.408
−0.931
−0.135
−0.641
−0.453
−0.899
3187760
11467922

hexylcaine
15.3
−0.243
−0.043
−1.093
−0.567
0.761
−0.287
−0.420
−0.510
−0.150
3187761
11467936

eucatropine
13.72
0.195
−0.577
−1.193
−0.394
0.182
0.279
−0.104
−0.052
−0.193
3187762
11467942

bucladesine
8.52
0.426
1.159
−2.045
−0.834
0.838
0.934
−0.946
−0.833
−1.003
3187884
11467961

lasalocid
6.78
−1.076
−2.539
−3.481
−1.518
−2.547
−2.028
−1.296
0.500
−4.696
3187885
11467976

novobiocin
6.52
−1.306
−0.242
−1.973
−0.828
1.037
−0.043
−0.582
−0.600
−0.427
3187886
11467982

iocetamic acid
6.52
−1.121
−0.565
−1.752
−0.748
1.244
−0.407
−0.226
−0.035
−0.572
3187887
11467986

securinine
18.42
−1.284
0.472
−2.816
0.636
−1.392
0.070
−0.934
−0.826
−0.973
3187888
11467989

nafcillin
9.66
−1.063
−0.049
−2.074
−0.851
0.785
−0.118
−0.589
−0.629
−0.392
3187889
11467991

doxycycline
9
−0.338
−0.232
−1.655
−1.288
1.003
−0.089
−0.415
−0.712
0.270
3187892
11468000

roxithromycin
4.78
0.271
0.042
−2.130
−0.519
0.795
0.424
−0.703
−0.378
−1.216
3187893
11468002

5-azacytidine
16.38
−1.939
−0.890
−3.989
−0.838
−0.821
−2.110
0.465
0.650
−0.001
3187895
11468014

paromomycin
6.5
−1.024
−0.332
−1.232
−1.035
1.005
0.513
−0.756
−0.592
−0.930
3187896
11468015

digoxigenin
10.24
0.352
2.192
−0.157
−0.237
0.038
0.884
−0.418
−0.283
−0.628
3187897
11468031

esculin
11.76
−0.845
0.709
0.034
−0.526
−0.253
0.588
0.048
0.031
0.077
3187898
11468040

adrenosterone
13.32
−0.047
0.462
1.012
−0.100
1.330
0.001
−0.298
−0.344
−0.159
3187899
11468047

ethynodiol diacetate
10.4
0.251
1.264
0.680
0.072
1.234
−1.332
−1.258
−1.144
−1.264
3187900
11468056

nizatidine
12.06
0.923
−0.251
−0.226
−0.390
−0.285
0.876
0.172
0.122
0.223
3188016
11468069

thioperamide
13.68
0.134
0.955
−0.938
−0.530
0.031
−0.025
−0.481
−0.535
−0.290
3188017
11468070

S(−)-terguride hydrogen
11.74
−1.081
0.209
−0.697
−0.459
0.735
0.125
1.039
0.914
1.095
3188018
11468075

S(−)eticlopride
11.74
0.195
−0.365
−1.030
−0.105
0.367
−0.169
−0.007
0.070
−0.164
3188019
11468080

bephenium
9
−0.206
−0.401
−0.544
−0.384
0.936
−0.043
0.013
−0.191
0.433
3188020
11468084

tyloxapol
4.02
0.048
0.309
−0.123
0.014
0.665
−0.039
0.169
0.067
0.332
3188022
11468102

6-hydroxytropinone
25.78
−0.058
2.418
0.313
0.515
0.507
0.933
−0.176
−0.044
−0.423
3188025
11468115

remoxipride
10.78
0.412
1.197
−0.924
−0.502
0.342
0.778
−0.300
−0.090
−0.700
3188026
11468119

nitrocaramiphen
11.96
0.636
1.010
−0.403
−0.360
0.003
0.296
−0.486
−0.317
−0.748
3188027
11468129

proscillaridin A
7.54
−0.350
0.760
−0.058
−0.665
1.100
0.573
0.136
0.127
0.122
3188028
11468134

asiaticoside
4.18
−0.462
−0.498
−0.364
0.214
0.488
0.220
0.444
0.334
0.571
3188029
11468137

ribavirin
16.38
−1.176
−0.010
−0.892
−0.068
0.401
−0.336
0.425
0.520
0.138
3188030
11468141

lymecycline
6.64
−0.275
−0.827
0.322
0.235
−0.269
−0.056
0.156
0.037
0.364
3188032
11468148

meptazinol
17.14
−0.371
−0.737
−0.711
−0.012
1.358
−0.071
−0.021
0.121
−0.334
3188033
11468152

apramycin
7.42
−0.376
0.061
−0.744
−0.663
0.886
−0.064
0.414
0.193
0.781
3188034
11468153

fursultiamine
10.04
−0.297
0.781
0.198
−0.739
0.489
0.477
0.675
0.704
0.489
3188035
11468155

pivampicillin
8.62
−0.907
−0.731
−0.242
−0.195
0.452
0.326
0.215
0.111
0.372
3188145
11468157

talampicillin
8.3
−0.644
−0.313
−0.118
0.120
−0.299
−0.064
0.676
0.417
1.074
3188146
11468158

flucloxacillin
8.82
0.149
0.368
−0.995
−0.072
0.823
0.272
−0.387
−0.177
−0.755
3188147
11468159

deptropine
12
0.164
−0.575
−0.027
−0.319
0.957
−0.026
0.748
0.530
1.045
3188148
11468161

tribenoside
8.36
0.273
−0.432
0.302
0.589
0.355
0.107
−0.039
−0.251
0.399
3188149
11468167

rimexolone
10.8
−0.123
−1.896
0.560
0.058
−0.447
−0.350
−0.005
−0.176
0.342
3188150
11468168

nifurtimox
13.92
−0.554
−1.006
−0.144
−0.499
0.669
0.004
0.156
0.144
0.127
3188151
11468172

tocainide
20.8
−0.990
−0.577
−0.707
−0.418
0.336
0.211
0.452
0.413
0.439
3188152
11468175

benzathine benzylpenicillin
6.78
−0.568
−0.853
−0.151
0.729
0.478
0.277
0.624
0.429
0.889
3188153
11468176

nomegestrol acetate
10.8
0.011
1.167
−0.220
−0.331
1.945
−0.425
1.104
1.008
1.082
3188154
11468181

alcuronium chloride
6.02
−0.672
0.112
−0.520
−0.463
0.312
0.391
−0.152
−0.149
−0.123
3188155
11468184

pyrvinium pamoate
5.18
−2.444
−4.764
−3.107
−2.252
−1.211
−0.619
−2.809
−1.358
−5.233
3188156
11468188

tridihexethyl
12.56
0.631
1.450
−0.048
−0.566
−1.685
0.959
0.063
0.309
−0.465
3188157
11468190

prednicarbate
8.18
−0.973
1.031
−0.689
−0.494
−0.656
0.113
−0.032
−0.228
0.356
3188158
11468192

repaglinide
8.84
0.419
0.849
−0.385
−0.401
−0.573
0.723
−1.063
−1.177
−0.642
3188159
11468194

piperacetazine
9.74
1.287
0.544
−0.961
−0.104
−0.798
0.357
0.480
0.543
0.253
3188160
11468196

pivmecillinam
9.1
0.383
0.785
−0.509
2.087
−0.149
−0.192
0.206
−0.058
0.683
3188161
11468201

levopropoxyphene
7.3
−0.556
0.558
−1.141
−0.877
0.058
0.181
−0.829
−1.100
−0.124
3188162
11468202

phensuximide
21.14
0.776
1.060
0.316
0.153
−0.510
0.760
−0.944
−1.050
−0.550
3188163
11468209

thiethylperazine
7.5
1.087
1.307
0.548
0.676
0.829
−1.615
−0.558
−0.644
−0.286
3188276
11468216

cyproterone acetate
9.6
−0.234
−0.262
−0.638
−0.339
0.871
0.055
−0.301
−0.342
−0.160
3188277
11468222

methiazole
15.08
−0.683
−0.555
−0.654
0.040
−2.515
−1.954
1.166
0.795
1.685
3188278
11468228

condelphine
8.9
0.090
−0.472
−0.983
−0.122
−0.040
−0.031
0.500
0.530
0.325
3188279
11468231

sulfadoxine
12.88
0.265
−0.471
−1.186
−0.176
−0.172
−0.293
−0.275
−0.323
−0.148
3188280
11468242

estriol
13.88
−0.462
0.043
−0.799
−0.415
−0.143
−0.136
−0.169
−0.210
−0.052
3188281
11468244

vitamin K2
8.96
0.095
−0.620
0.693
−0.246
−0.635
−0.948
0.517
0.427
0.587
3188282
11468248

natamycin
6
−0.005
−0.227
−0.063
−0.106
0.170
−0.163
0.161
0.105
0.232
3188283
11468252

verteporfin
2.78
0.583
−1.600
−0.058
−2.961
−0.198
−0.244
0.741
0.809
0.457
3188284
11468253

rifabutin
4.72
−0.144
−0.839
0.603
0.786
0.049
−0.840
0.745
0.413
1.276
3188285
11468257

viomycin
5.84
0.648
0.473
−0.224
0.073
−0.798
−0.234
1.247
1.176
1.142
3188286
11468261

cefepime
8.3
0.811
−1.403
−0.041
0.260
−0.739
−0.735
1.443
1.218
1.609
3188288
11468266

clocortolone
8.08
0.343
−0.909
0.908
1.141
−0.386
−1.321
1.361
0.981
1.863
3188289
11468267

benzonatate
6.62
−0.010
1.591
−1.144
−0.380
0.562
0.594
−0.671
−0.604
−0.726
3188932
11467160

norethynodrel
13.4
−0.683
0.040
−1.593
−0.453
0.988
−0.145
−0.575
−0.567
−0.521
3188934
11467172

chloramphenicol
12.38
0.041
0.012
−1.351
−1.241
0.363
−0.276
−0.415
−0.617
0.035
3188935
11467179

troleandomycin
4.92
−1.093
0.763
−1.080
−0.855
1.244
−0.032
0.205
0.260
0.011
3188936
11467184

amyleine
17
−0.948
0.509
−0.719
−0.888
1.284
−0.010
−0.235
−0.182
−0.344
3188937
11467197

morantel
10.8
−1.011
−0.170
0.027
−0.644
1.553
0.004
−0.640
−0.520
−0.810
3188938
11467209

sulindac
11.22
0.982
0.828
−1.084
−0.456
1.076
−0.390
0.241
0.442
−0.266
3188939
11467221

ursolic acid
8.76
1.135
2.069
−0.501
−0.433
−0.570
0.667
−0.218
−0.106
−0.440
3188940
11467237

danazol
11.86
0.059
1.289
−0.696
0.440
0.542
0.651
0.205
0.123
0.281
3189048
11467253

atropine-n-oxide
13.1
−0.171
0.490
−0.526
−0.805
0.320
0.395
−0.205
−0.157
−0.305
3189049
11467255

naltrexone
11.72
−0.597
0.242
−1.150
−0.694
0.452
−0.098
−0.521
−0.758
0.025
3189051
11467264

dehydrocholic acid
9.56
−0.337
0.386
−1.619
−0.202
0.099
−0.074
−1.516
−1.635
−1.014
3189053
11467271

spironolactone
9.6
−0.906
0.240
−0.480
−0.546
0.249
−0.651
−0.105
0.044
−0.411
3189054
11467276

clindamycin
9.42
−0.784
0.714
−1.753
−0.367
0.094
−0.521
−1.034
−1.119
−0.693
3189055
11467285

thioproperazine
8.96
0.575
−0.214
−0.194
−0.529
0.718
−0.407
−0.507
−0.801
0.153
3189056
11467297

dihydroergotamine
5.46
−0.725
−0.209
−0.231
0.841
0.611
−1.645
0.412
0.132
0.881
3189057
11467298

oleandomycin
5.82
0.233
0.659
−0.409
−0.099
−0.639
−0.018
0.882
0.744
0.940
3189058
11467300

midecamycin
4.92
0.343
0.896
−0.097
−0.840
−0.304
0.023
0.150
−0.103
0.585
3189059
11467301

paclitaxel
4.68
−0.352
−1.276
−2.576
0.116
−2.010
−2.115
0.949
0.708
1.198
3189060
11467303

ivermectin
4.58
1.161
−0.341
−0.291
−0.399
1.009
−0.498
0.172
0.099
0.242
3189061
11467304

gentamicin sulfate
2.88
0.282
−0.078
1.215
−0.159
−0.043
−0.598
−0.261
−0.551
0.334
3189062
11467308

aztreonam
9.18
−0.470
1.025
−1.241
−0.942
1.032
0.273
−0.408
−0.571
−0.033
3189063
11467333

metaraminol
12.6
−0.545
0.255
−1.192
−0.885
1.545
−0.275
0.171
0.082
0.274
3189174
11467345

kawain
17.38
−0.826
0.038
−1.416
−1.000
0.871
−0.681
−0.157
−0.280
0.089
3189175
11467355

antimycin A
7.3
−0.827
−2.124
−1.958
1.345
−0.522
−0.969
−1.672
−1.695
−1.341
3189176
11467370

metampicillin
11.06
−0.887
−0.115
−1.317
−0.251
0.596
−1.458
0.191
0.044
0.400
3189177
11467383

ethisterone
12.8
0.267
0.413
−0.499
−0.358
0.302
0.300
−0.791
−0.715
−0.796
3189178
11467409

dimenhydrinate
8.52
−0.635
0.833
−0.855
−1.013
1.119
0.608
0.278
0.457
−0.146
3189179
11467413

prednisolone
11.1
−1.328
−0.308
−1.828
−0.554
0.245
−0.416
−0.025
−0.049
0.023
3189180
11467422

enalapril
10.62
−0.217
−0.181
−1.135
−0.279
0.063
0.141
0.135
0.147
0.086
3189181
11467462

streptomycin
6.88
−0.709
1.103
−0.569
0.421
−0.156
1.292
−0.195
−0.020
−0.503
3189183
11467469

zidovudine
14.92
−0.277
2.049
−1.301
−0.832
0.693
0.611
0.221
0.245
0.133
3189185
11467481

N6-methyladenosine
14.22
0.521
0.971
−0.288
−0.239
0.965
0.596
0.803
0.957
0.337
3189186
11467486

thioguanosine
13.36
−0.142
0.430
−1.708
−0.267
0.834
0.005
0.780
1.042
0.105
3189187
11467495

amoxicillin
10.94
−1.094
0.476
−0.685
−0.693
1.552
0.139
0.314
0.298
0.294
3189189
11467505

bambuterol
10.88
0.478
−0.493
−0.552
−0.875
0.748
0.143
0.453
0.345
0.599
3189191
11467509

brinzolamide
10.42
−0.711
0.392
−1.598
−0.796
1.002
−0.139
0.014
0.070
−0.109
3189192
11467513

methylergometrine
11.78
−1.118
−0.424
−1.251
−0.948
1.095
0.182
−0.599
−0.558
−0.565
3189193
11467522

etoposide
6.8
−0.733
−0.245
−1.910
−0.448
−0.516
−0.260
0.735
0.469
1.126
3189304
11467544

oxantel
6.62
−0.307
−0.303
0.069
−1.789
2.405
0.178
0.807
0.605
1.067
3189305
11467546

hesperidin
6.56
−0.109
0.592
0.329
−0.156
0.911
0.353
0.459
0.197
0.892
3189306
11467548

pepstatin A
5.84
0.272
0.859
−0.763
−0.700
0.397
1.091
−0.305
−0.067
−0.728
3189307
11467553

androsterone
13.78
0.293
0.555
−0.542
−0.544
−0.164
0.841
−1.093
−0.771
−1.544
3189308
11467559

bacampicillin
8.6
0.192
0.158
−0.881
−0.977
0.213
0.445
0.160
0.264
−0.076
3189309
11467564

calciferol
10.08
−0.074
−0.555
0.282
0.381
0.970
−1.054
0.001
0.279
−0.562
3189310
11467568

7-aminocephalosporanic acid
14.7
−0.180
0.799
−1.256
−0.191
0.654
0.670
−0.100
0.110
−0.520
3189311
11467572

cholecalciferol
10.4
−0.573
−0.364
−0.562
−0.198
0.659
−0.194
0.024
0.157
−0.255
3189312
11467577

cyanocobalamin
2.94
−1.085
0.632
−1.478
−0.846
0.328
0.329
−1.209
−0.985
−1.421
3189313
11467581

digitoxigenin
10.68
−0.888
−0.339
−1.229
−0.512
0.438
−0.073
0.114
0.247
−0.179
3189314
11467584

digoxin
5.12
−1.317
0.912
−1.162
−0.870
0.627
0.169
0.511
0.657
0.121
3189315
11467585

gabazine
13.92
−0.773
0.684
−1.804
−0.345
0.313
−0.094
−0.494
−0.441
−0.502
3189316
11467591

ginkgolide A
9.8
−0.812
−0.907
−1.701
−0.670
0.029
−0.161
−0.704
−0.408
−1.173
3189317
11467592

lactobionic acid
11.16
−0.062
−0.424
−1.181
−0.327
0.417
0.269
−0.083
0.142
−0.540
3189433
11467600

cefixime
8.82
0.849
0.599
−0.047
−0.353
0.348
0.331
−0.428
−0.422
−0.365
3189434
11467610

N-acetylmuramic acid
13.64
0.270
−0.262
−1.311
−0.425
−0.130
−0.122
−0.073
0.112
−0.435
3189435
11467612

cefotetan
6.94
0.369
−0.725
−0.324
−0.081
−0.647
0.186
0.496
0.489
0.408
3189436
11467621

puromycin
8.48
−5.640
−8.529
−6.198
−3.529
−3.921
−5.832
−1.590
−2.800
1.240
3189437
11467628

6-azathymine
31.48
1.057
2.625
−0.772
−0.350
−0.053
0.583
−0.464
−0.176
−0.964
3189438
11467631

colistin
3.46
0.940
1.795
−1.283
−0.746
0.501
0.409
−0.341
−0.016
−0.939
3189439
11467634

ceftazidime
7.3
0.992
0.957
−0.654
−0.673
−0.209
0.740
−0.379
−0.056
−0.965
3189440
11467637

terconazole
7.52
0.751
0.127
−3.209
−0.196
1.691
0.552
−1.032
−0.870
−1.158
3189441
11467643

etifenin
12.4
0.228
1.009
−1.084
−0.738
0.798
0.092
−0.666
−0.698
−0.477
3189442
11467652

nystatine
4.32
−0.430
0.370
−1.147
−0.660
0.765
0.061
−0.436
−0.272
−0.683
3189443
11467665

thiostrepton
2.4
−0.979
−0.925
−2.771
−0.160
−0.494
−1.134
0.357
−0.162
1.338
3189444
11467670

rifampicin
4.86
−0.591
−0.681
−1.866
−0.918
−0.224
0.319
−0.270
−0.071
−0.620
3189445
11467673

thiocolchicoside
7.1
−0.498
−0.617
−0.850
−0.168
1.037
0.108
−0.170
−0.099
−0.282
3189446
11467687

dirithromycin
4.8
−1.308
−0.295
−0.838
−0.880
0.463
0.356
−0.324
−0.298
−0.311
3189565
11467705

tubocurarine
6.56
−1.217
2.248
0.659
0.044
0.229
1.117
−0.267
−0.426
0.104
3189566
11467709

aconitine
6.2
−0.184
1.375
−0.538
−0.393
0.623
1.609
0.389
0.414
0.249
3189567
11467715

emetine
8.32
−4.480
0.048
−3.433
1.294
−2.661
−1.644
−0.023
2.313
−4.790
3189569
11467718

tomatidine
9.62
−0.422
0.996
−0.985
−0.311
0.586
1.135
−0.158
0.010
−0.443
3189571
11467721

(+)-chelidonine
11.32
−1.005
−0.045
−1.988
−1.123
−1.486
−1.144
0.941
0.901
0.836
3189572
11467735

tetrahydroalstonine
11.34
0.055
−0.199
−1.505
−1.309
1.058
1.439
−0.219
−0.294
−0.016
3189573
11467741

cinchonidine
13.58
−1.586
−0.657
−1.384
−1.067
0.411
−0.164
−0.385
−0.183
−0.717
3189574
11467754

canavanine
22.7
−0.510
−0.289
−1.333
−0.640
0.992
−0.321
−0.178
−0.262
0.032
3189575
11467757

demecarium
7.18
0.880
−0.356
−1.431
−0.664
0.088
−0.211
−0.552
−0.515
−0.517
3189576
11467764

cytisine
21.02
−0.534
−0.789
−0.118
−0.704
1.404
0.095
0.025
0.181
−0.295
3189578
11467772

racecadotril
10.38
−0.468
−0.182
−1.550
−0.382
0.705
−0.249
−0.249
−0.229
−0.235
3189579
11467774

salsolinol
22.32
−1.127
0.469
−1.113
−0.160
−0.248
−0.994
−0.284
−0.197
−0.397
3189580
11467776

dimethisoquin
14.68
0.300
−0.047
−0.838
−0.222
1.731
−1.006
0.302
0.140
0.575
3189581
11467778

hydroquinine
12.26
0.231
0.044
−1.378
−0.193
1.619
0.004
0.151
−0.044
0.529
3189582
11467783

avocatin A
20
0.133
0.371
−0.249
−0.057
0.404
0.849
−1.145
−1.066
−1.140
3198309
11487988

(−)-duartin
20
1.175
0.719
−0.571
0.392
0.900
−0.472
−0.048
−0.331
0.466
3198310
11488036

fumarprotocetraric acid
20
−0.955
1.131
−0.538
−0.590
0.476
0.505
−0.527
−0.553
−0.327
3198311
11488203

canrenone
20
0.025
0.952
−0.644
−0.307
−0.063
0.816
−0.663
−0.842
−0.123
3198312
11488300

madecassic acid
20
0.982
0.701
−0.798
0.374
−0.132
0.241
0.505
0.493
0.468
3198313
11488304

telithromycin
20
0.318
−0.039
−1.062
−0.146
0.922
−0.023
−0.489
−0.624
−0.079
3198314
11488325

deracoxib
20
1.524
0.320
−0.588
−0.313
0.081
0.350
0.250
0.179
0.386
3198315
11488337

troxerutin
20
−0.194
−0.263
−1.235
−0.072
0.153
−0.673
−1.220
−1.161
−1.059
3198316
11488345

trandoapril
20
0.694
0.603
−0.684
−0.210
0.572
0.687
−1.375
−1.466
−0.884
3198317
11488397

zearalenone
20
0.576
0.541
−0.900
−0.194
2.122
−0.185
−0.979
−0.810
−1.159
3198318
11488475

securinine
20
−1.075
0.292
−0.269
0.949
−1.553
−0.481
0.346
0.370
0.201
3198319
11488485

oxiconazole
20
−3.228
−3.585
−1.535
1.299
−1.503
−3.509
−1.477
−1.697
−0.747
3198320
11488514

elaidylphosphocholine
20
−0.314
−0.183
−0.962
−0.415
0.720
−0.840
−0.464
−0.352
−0.618
3198321
11488524

cobalamine
20
−0.821
−0.685
−1.369
0.097
2.944
−0.617
−0.402
−0.373
−0.393
3198322
11488530

derrustone
20
−0.982
−0.355
−1.694
−0.126
0.664
0.470
−0.764
−0.685
−0.797
3198323
11488579

rutoside
20
−0.964
0.370
−1.155
−1.012
0.172
−0.012
−0.338
−0.575
0.188
3198324
11488595

5,4′-dimethoxy-7-hydroxyflavone
20
−0.171
−0.900
−0.913
−0.043
1.747
0.173
0.083
−0.073
0.369
3198325
11488611

endecaphyllin X
20
0.158
0.525
−1.007
0.142
−0.292
−0.219
−0.660
−0.566
−0.741
3198326
11488622

palmatine
20
−1.028
0.565
−1.222
−0.823
0.511
−0.084
1.822
1.636
1.833
3198419
11488652

vinblastine
20
1.466
−0.803
−2.171
0.665
−1.327
−1.078
2.083
2.088
1.636
3198420
11488706

pravastatin
20
−0.787
0.476
−1.703
−0.625
1.093
0.972
−0.671
−0.508
−0.890
3198421
11488729

hygromycin B
20
−1.526
0.370
−2.041
−0.752
0.707
−0.478
0.558
0.800
−0.054
3198422
11488734

gemifloxacin
20
−0.578
0.647
−1.445
−1.057
0.992
0.009
0.256
0.287
0.203
3198423
11488908

triflupromazine
20
−0.120
−0.080
−0.255
−0.897
1.928
0.141
0.433
0.224
0.845
3198424
11488935

topiramate
20
0.452
1.483
−0.732
−0.212
−0.360
−0.093
0.255
0.302
0.178
3198425
11488944

4-amino-3-(5-chlorothien-2-yl)butanoic acid
20
0.201
−0.117
−1.056
−0.276
0.170
0.593
0.343
0.489
0.039
3198426
11488987

nonoxynol-9
20
−0.209
−0.737
−1.228
−1.484
0.528
0.189
−0.872
−1.114
−0.138
3198427
11489063

trandolapril
20
−1.323
0.195
−0.581
−0.681
0.745
0.039
−0.241
−0.174
−0.259
3198428
11489065

megestrol acetate
20
0.546
0.297
0.296
−0.108
0.692
0.810
0.106
0.170
0.024
3198429
11489087

TFA-Val-Tyr-Val-OH
20
−0.143
0.751
−1.019
−0.510
0.471
−0.785
0.294
0.415
−0.008
3198430
11489302

valyltryptophan
20
−1.481
−0.053
−0.468
−0.438
0.388
−0.626
−0.534
−0.551
−0.381
3198431
11489304

S-methyl-L-thiocitrulline acetate
20
0.613
1.060
−0.262
−0.542
0.052
0.533
0.291
0.325
0.173
3198432
11489307

N-histidyl-2-aminonaphthalene
20
−0.137
0.371
−0.147
−0.618
0.353
0.214
−0.595
−0.469
−0.739
3198433
11489308

lysylphenylalanyltyrosine
20
−0.701
1.158
−1.300
−0.825
0.225
0.240
−0.424
−0.208
−0.783
3198434
11489310

phenylalanyltyrosine
20
−0.068
0.102
−0.574
−1.085
0.132
−0.342
−0.424
−0.366
−0.465
3198435
11489312

selamectin
20
0.300
0.856
−0.348
−0.467
0.641
0.343
−0.112
0.126
−0.565
3198436
11489399

citicoline
20
−0.283
0.203
−0.605
−0.103
1.034
0.322
−0.620
−0.607
−0.495
3198437
11489507

icariin
20
−0.001
0.072
−2.441
−0.784
0.775
0.073
0.578
0.656
0.331
3198531
11489511

oxfendazole
20
0.107
−0.524
−2.568
−0.446
0.692
−0.224
−0.801
−0.626
−0.969
3198532
11489520

chlorophyllide
20
−0.178
0.439
0.307
−0.783
1.042
−1.157
0.282
0.303
0.224
3198533
11489524

avocatin B
20
−0.869
−0.292
−1.119
0.024
1.229
0.710
−0.935
−0.863
−0.852
3198534
11489534

1,3-dideacetyldeoxykhivorin
20
−0.409
0.176
−0.507
0.283
1.279
0.007
−0.370
−0.392
−0.207
3198535
11489535

neopine
20
−1.240
0.172
−1.068
−0.640
0.784
0.421
−0.701
−0.866
−0.183
3198536
11489561

totarol-19-carboxylic acid
20
−0.506
−1.295
−1.701
−0.008
−0.209
−1.116
−0.399
−0.494
−0.073
3198537
11489564

milldurone
20
−0.401
0.268
−0.713
−0.569
0.680
0.465
0.343
0.605
−0.215
3198538
11489569

gambogic acid
20
−5.389
−8.341
−6.656
−4.102
−4.200
−5.596
−3.830
−4.010
−2.680
3198539
11489625

methyl gamboginate
20
−2.359
0.086
−2.730
−0.307
0.282
−0.800
−0.567
−0.507
−0.533
3198540
11489646

lanosterol
20
0.020
0.124
−1.103
−0.503
0.879
0.383
−0.156
−0.293
0.207
3198541
11489712

dioonflavone
20
−0.003
0.062
−0.744
0.208
0.650
0.605
−0.471
−0.204
−0.969
3198542
11489742

sodium salicylate
20
−0.836
0.123
−0.890
−0.996
0.435
0.607
−0.164
−0.086
−0.341
3198543
11489761

3beta-hydroxy-23,24-bisnorchol-5-enic acid
20
−0.295
0.219
−0.244
−0.402
0.315
−0.309
0.756
0.793
0.486
3198544
11489765

p-hydroxycinnamaldehyde
20
−1.650
0.701
−1.942
−0.918
0.120
−0.079
−1.097
−1.113
−0.889
3198545
11489779

geranyl cinnamate
20
−0.653
0.124
−1.080
−0.515
1.250
−0.107
−0.697
−0.668
−0.652
3198546
11489791

telmisartan
20
2.326
−0.755
−0.800
−0.028
2.637
−0.044
−0.648
−0.802
−0.253
3198547
11489792

7-[2-trifluoromethyl-4-(2-hydroxyphenyl)-1,3-
20
−0.413
0.276
−0.548
−0.087
0.713
−0.437
0.344
0.169
0.594
3198548
11489816

dioxan-cis-5-yl]-hept-5z-enoic acid

diprotin A
20
−0.788
−0.247
−1.068
0.357
0.300
−0.975
0.099
−0.102
0.490
3198954
11489296

bissalicyl
20
−0.317
1.023
−1.349
−0.161
0.356
0.551
0.047
0.014
0.046
3199904
11487821

rifaximin
20
1.755
0.212
−0.813
0.910
1.073
−0.471
0.411
0.282
0.541
3199905
11487836

tylosin
20
−0.554
0.778
−1.239
−0.550
1.188
−0.007
−0.376
−0.466
−0.179
3199906
11487843

sarafloxacin
20
−0.337
−0.345
−2.298
−0.519
0.763
0.290
0.312
0.416
−0.017
3199907
11487852

atracurium
4.3
0.005
1.412
−0.223
0.509
0.755
1.176
0.530
0.626
0.182
3221455
11467153

bacitracin
2.82
−0.938
0.616
−0.310
−0.214
0.105
−0.806
−0.592
−0.736
−0.189
3221506
11468067

N-acetylaspartylglutamic acid
20
0.010
0.503
0.280
−0.393
−0.197
0.480
−0.126
−0.008
−0.342
3471022
11489297

cephaloridine
20
−0.905
0.237
−1.458
−0.963
0.543
−0.278
−0.664
−0.802
−0.269
3471036
11488739

cefsulodin
20
−0.348
−0.481
0.132
−0.784
1.553
−1.078
0.455
0.516
0.204
3471107
11489766

kanamycin A
8.26
−1.015
−0.738
−1.149
−0.812
1.383
−0.131
−0.270
−0.218
−0.323
3471415
11467542

ipratropium
12.04
−0.371
1.816
−1.408
−0.475
0.931
0.674
0.000
0.242
−0.496
3471597
11467723

isoxsuprine
13.28
−1.004
−0.293
−1.833
−0.947
1.652
−0.148
0.888
0.827
0.800
3471598
11467216

metampicillin
20
0.609
1.047
−0.182
−0.390
−0.119
0.821
−0.247
−0.019
−0.623
3471725
11488357

bergenin
12.18
0.555
0.898
−1.415
−0.637
0.880
0.831
−0.379
−0.421
−0.232
3472295
11467959

dehydroepiandrosterone
20
−0.999
0.584
−0.731
−0.137
0.596
−0.634
−0.139
−0.151
−0.033
3472730
11488175

atovaquone
10.9
−0.567
−1.627
−2.368
0.488
0.773
−0.124
−0.505
−0.281
−0.870
3474094
11467682

venlafaxine
20
0.301
0.691
−0.751
−0.685
0.030
0.627
−0.521
−0.450
−0.517
3474304
11488358

gliclazide
12.36
−0.452
−0.234
−0.090
−0.608
0.915
0.147
−0.779
−0.812
−0.565
3474312
11467706

mepivacaine
20
−0.497
−0.150
−0.686
−0.945
0.411
−0.084
−0.780
−0.625
−0.907
3474314
11489472

isradipine
10.78
−0.674
−0.597
−0.635
0.349
0.522
0.236
0.070
−0.063
0.317
3480040
11468169

ritodrine
20
−0.827
0.439
−0.706
−1.368
0.742
−0.072
−0.221
−0.352
0.089
3480067
11489239

pioglitazone
20
0.749
−1.224
−0.352
−0.421
1.512
−0.742
0.579
0.500
0.657
3480074
11489495

tolterodine
20
−0.490
0.228
−0.729
−1.032
0.472
−0.406
0.049
0.113
−0.050
3480078
11488342

carvedilol
20
0.453
−4.716
−5.765
−3.375
−2.321
−4.745
−2.460
−2.817
−1.246
3480079
11489489

fexofenadine
20
−0.364
0.563
−0.823
−0.223
0.678
−0.751
0.057
0.173
−0.113
3480106
11488995

sibutramine
20
−1.609
−0.196
−1.556
0.798
0.451
0.351
0.804
0.846
0.583
3480112
11489502

procaterol
20
0.002
0.084
−1.049
−0.363
0.795
−0.168
0.094
0.298
−0.336
3480197
11489366

alfluzocin
10.28
0.072
1.978
−0.139
−0.124
−0.245
−0.145
−0.458
−0.212
−0.858
3480229
11467470

alfluzocin
20
0.315
1.565
−1.047
−0.209
0.139
0.781
−0.237
−0.339
0.063
3480229
11488321

amlodipine
20
0.030
−0.359
−1.287
0.003
−0.179
0.902
−1.328
−1.512
−0.655
3480246
11488302

felodipine
10.4
1.052
0.006
−1.229
0.540
−0.682
−0.956
0.477
0.498
0.341
3480329
11467626

rebamipide
20
−0.517
0.492
−1.340
−0.129
0.967
−0.372
−0.100
−0.328
0.331
3480338
11487855

bifonazole
20
−0.063
0.122
−1.879
−0.622
0.552
0.179
−0.276
−0.492
0.173
3480340
11487851

azelastine
20
0.001
1.381
0.174
1.404
0.268
0.054
−0.315
−0.467
0.015
3480341
11488465

betaxolol
13.02
−0.889
−0.479
−0.648
−0.507
0.759
0.064
−0.317
−0.309
−0.273
3480396
11467530

dobutamine
13.28
−0.245
−0.138
−1.063
−1.373
−0.132
−0.289
−0.285
−0.059
−0.683
3480458
11467500

oxybutynin
11.18
−0.493
0.338
−0.644
−0.981
0.547
−0.352
0.372
0.466
0.112
3480597
11467435

naftopidil
10.2
0.654
−0.095
−0.214
0.133
1.396
0.382
0.786
0.810
0.572
3480607
11468123

sotalol
14.68
−0.754
0.583
−0.390
0.105
0.305
0.501
0.744
0.885
0.299
3480627
11468114

dipivefrin
11.38
0.377
0.101
−0.661
−0.606
0.841
−0.180
0.218
0.096
0.416
3487152
11467780

nitrarine
13.02
−0.068
−0.894
−1.978
−0.986
0.458
0.040
−0.352
−0.303
−0.378
3487155
11467833

proxyphylline
16.78
0.659
2.332
0.395
0.821
−0.186
−0.574
0.111
0.174
−0.056
3487233
11468038

iodixanol
2.58
−0.580
0.017
−2.238
−0.651
1.280
−0.092
−0.422
−0.534
−0.114
3487254
11467996

iopromide
5.06
−0.774
0.451
−0.350
0.132
0.278
0.263
0.087
0.130
−0.020
3487261
11468020

ioversol
4.96
−0.567
−1.318
−0.842
−0.693
0.319
0.129
0.110
0.000
0.310
3487262
11468026

isoconazole
9.62
−0.442
−0.920
−2.216
−0.823
1.342
−0.572
−1.056
−1.233
−0.525
3487389
11467275

hydroxyzine
10.66
0.793
1.036
−1.043
0.143
0.020
0.258
−1.077
−0.878
−1.323
3487390
11467281

chlorphensin
16.28
−1.132
−0.429
−0.356
−0.419
0.692
−0.522
−0.696
−0.613
−0.766
3487401
11467382

bisoprolol
12.3
0.314
1.423
0.031
0.986
0.513
0.874
0.633
0.607
0.564
3487402
11467478

cisapride
8.58
0.305
0.764
0.523
0.763
2.245
−0.495
−0.329
−0.231
−0.468
3487430
11467578

tiaprofenic acid
15.36
−0.148
0.041
−1.167
−1.012
1.746
0.644
0.111
0.379
−0.452
3487464
11467644

cetirizine
10.28
0.234
1.442
−1.107
−0.943
0.568
0.507
−0.690
−0.499
−0.955
3487465
11467651

syrosingopine
6
−0.660
2.649
−0.077
0.479
0.586
1.051
−0.123
−0.010
−0.336
3487467
11467712

penbutolol
13.72
0.287
−0.825
−1.020
0.436
−0.960
0.099
−1.251
−1.184
−1.143
3487585
11468191

netilmicin
8.42
0.633
−0.654
0.883
−0.582
−0.762
0.156
1.032
0.861
1.167
3487604
11468249

TABLE 3

Top Compounds identified in screen

ROS

Plate
Well
Compound Name
ChemBankID
PubChem_CID
GEHTS_Zscore
Zscore

2163
A04
podophyllotoxin
3177591
164791
3.506
−1.656

acetate

2160
P17
podofilox
1001531
10607
3.408
−1.436

2160
B22
vinblastine sulfate
3198420
6710780
3.171
−1.327

2162
I04
mebendazole
1350
4030
2.846
−1.003

2161
H22
cytochalasin e
3063989
6711190
2.827
−2.109

2164
D21
Nocodazole
440
4122
2.675
−1.099

2158
H15
deoxysappanone b
2060294
4026888
2.577
−1.712

7,3′-dimethyl ether

2160
P05
paclitaxel
1000045
441276
2.451
−1.967

TABLE 4

Compounds Clustered According to Structural Similarity

GE-

Cluster ID
Compound Name
Viability
ATP
MTT
ΔΨ_m
ROS
HTS
nucOX
mitoOX
CpdAnno
AssayAnno

A
nigericin
−1.744
−3.165
−3.329
1.324
−3.323
15.99
8.185
3.884
ionophore
low ROS

A
salinomycin
−0.247
−3.542
−2.918
2.976
−3.111
16.48
8.804
3.303
antibiotics
low mitoOX

A
lasalocid
−1.090
−0.906
−1.771
−1.178
−2.993
16.84
9.753
2.812

A
monensin
−0.176
−3.394
−2.104
3.603
−2.989
19.54
10.821
3.782

A
lasalocid
−1.076
−2.539
−3.481
−1.518
−2.547
18.63
10.778
3.022

A
monensin
−0.307
−3.555
−3.197
1.556
−1.933
19.79
11.026
3.346

A
heudelottin C
−0.829
0.840
−0.393
0.373
0.576
18.96
9.187
5.034

B
dihydrorobinetin
−1.070
0.456
−1.259
−3.396
−0.393
18.80
9.311
5.214
flavonoid
low ΔΨm

B
epiafzelechin(2r,3r)(−)
−0.719
0.986
−0.486
−3.118
1.019
20.49
9.928
5.722
antioxidants

B
baicalein
−0.456
1.556
−1.632
−2.552
0.851
21.13
10.195
6.020

B
morin
−0.962
1.309
−0.293
−2.534
0.880
18.32
8.923
5.186

B
quinalizarin
0.583
1.276
−0.668
−2.511
0.674
20.11
9.896
5.429

B
epigallocatechin
−1.489
0.559
−1.197
−2.502
−0.531
19.18
9.279
5.345

B
kaempferol
−0.013
0.060
−0.352
−2.485
−1.322
18.55
8.957
5.283

B
purpurin
−1.205
−0.402
−2.248
−2.389
1.584
19.79
9.618
5.366

B
epicatechin
−1.657
0.915
−1.727
−2.362
0.513
18.24
8.400
5.134

B
epicatechin
0.077
2.069
−1.037
−1.966
−0.231
19.50
9.695
5.538

B
catechin hydrate
0.165
1.848
−1.301
−1.926
0.880
19.43
9.516
5.237

B
hieracin
1.425
0.806
−0.557
−1.902
−0.329
18.19
8.966
5.035

B
cianidanol
0.630
1.283
−1.471
−1.746
−0.371
18.69
8.815
5.387

B
quercetin
0.816
0.716
−1.595
−1.691
0.374
19.48
9.572
5.157

B
fisetinidol
−1.412
0.542
−1.804
−1.528
−0.215
17.44
8.389
5.079

B
luteolin
−0.627
−0.637
−0.209
−1.473
0.247
20.55
9.757
5.734

B
quercetin
0.686
0.361
−0.928
−1.240
0.615
19.22
9.135
5.517

B
hematein
−0.357
−0.036
−1.726
−1.215
0.835
19.45
9.571
5.445

B
haematoxylin
−1.044
0.382
−1.335
−1.035
0.225
19.97
10.054
5.184

B
fisetin
−0.764
0.456
−0.689
−0.893
0.442
20.40
9.947
5.701

B
1,4,5,8-tetrahydroxy-2,6-
−0.853
−0.346
−0.344
−0.662
0.772
19.02
9.187
5.408

dimethylanthroquinone

B
hesperetin
−0.764
0.123
−1.157
−0.650
0.147
20.24
10.051
5.339

B
hesperetin
−0.860
−0.368
−1.684
−0.633
0.674
18.29
9.086
5.049

B
naringenin
0.350
0.892
−0.475
−0.620
0.735
19.92
9.713
5.678

B
brazilin
−1.426
1.655
−1.218
−0.602
−1.481
18.48
9.653
4.329

B
brazilein
−1.633
0.713
−0.725
−0.110
1.078
21.92
10.798
5.914

B
naringenin
−1.071
1.514
−0.626
0.510
0.248
18.54
9.387
4.838

B
rhamnetin
−1.211
1.672
−0.975
0.717
0.228
18.77
9.107
4.892

C
methiazole
−0.683
−0.555
−0.654
0.040
−2.515
21.38
10.254
6.329
azole
low ROS

C
parbendazole
0.211
−1.119
−1.477
0.418
−1.879
22.47
10.896
6.039
antifungals
high GE-

HTS

C
albendazole
−0.402
0.854
−1.894
−0.296
−1.434
22.89
11.463
6.157

C
oxibendazole
−1.899
−0.104
−3.046
−0.975
−1.178
22.00
10.650
6.001

C
nocodazole
−0.069
−0.969
−0.751
0.358
−1.099
24.00
11.901
6.018

C
mebendazole
0.512
−0.483
−2.060
−0.434
−1.003
23.99
11.892
6.199

C
fenbendazole
−1.112
−0.672
−3.590
−0.395
−0.919
19.84
9.743
5.662

C
fenbendazole
−0.398
−1.895
−3.769
−0.360
−0.797
20.00
9.639
5.307

C
mebendazole
0.064
0.344
−2.797
−0.054
−0.791
20.64
10.038
5.807

C
oxfendazole
0.107
−0.524
−2.568
−0.446
0.692
19.75
9.847
5.320

D
tetracycline
−0.461
0.284
0.314
−1.031
0.987
21.80
10.191
6.473
tetracycline
high mitoOX

D
tetracycline
−0.405
−0.099
0.144
−0.854
0.275
20.20
9.449
6.270
antibiotics

D
oxytetracycline
0.029
−0.781
−1.129
−1.245
0.484
20.78
9.797
6.201

D
minocycline
−0.640
1.387
−1.103
0.117
1.514
20.98
10.284
5.684

D
demeclocycline
0.335
−0.475
−0.417
−0.818
0.335
21.29
10.237
6.045

D
methacycline
−1.645
−0.365
−1.744
−1.616
1.083
20.33
9.809
5.879

D
doxycycline
−0.322
−0.568
−1.407
−1.355
0.943
18.86
8.814
5.904

D
methacycline
0.323
2.538
−0.031
−0.517
0.261
20.94
10.237
5.945

D
oxytetracycline
0.398
1.384
−1.134
0.039
0.702
20.51
9.899
5.871

D
doxycycline
−0.338
−0.232
−1.655
−1.288
1.003
20.22
9.380
5.847

D
chlortetracycline
−0.009
−0.150
−0.740
−0.228
0.234
21.40
10.451
5.743

D
demeclocycline
−0.733
−0.208
−2.363
−1.613
0.110
19.66
9.508
5.697

D
minocycline
−0.150
1.286
−0.919
−0.905
1.108
20.42
9.867
6.073

D
chlortetracycline
0.391
0.875
0.026
0.339
−0.390
19.78
9.695
5.244

E
dihydrorotenone
0.390
−5.350
−4.020
−0.314
−0.682
14.76
6.664
4.180
rotenone
low ATP

E
isorotenone
−1.954
−5.273
−4.373
−1.329
−0.782
12.12
5.742
2.595
derivatives

E
deguelin(−)
−0.940
−5.123
−4.052
1.451
0.426
16.15
7.372
4.719

E
rotenone
−2.235
−4.842
−4.233
−2.300
−0.346
16.19
8.115
4.027

E
mundulone
−1.113
−4.544
−2.487
3.037
−0.141
15.32
7.065
4.571

E
alpha-toxicarol
0.304
−2.946
−1.982
0.820
0.101
21.85
10.719
5.672

E
beta-dihydrorotenone
−0.184
−2.497
−2.771
1.079
0.122
17.81
8.284
4.802

E
griseofulvin
0.008
−2.024
−1.919
0.065
−1.037
19.49
9.294
5.612

E
beta-toxicarol
0.672
−2.000
−1.498
0.899
−0.188
16.36
7.629
5.026

E
2-ethoxycarbonyl-2-
0.511
−1.500
−0.260
0.215
0.774
19.83
9.493
5.331

hydroxy-5,7-

dimethoxyisoflavanone

E
griseofulvic acid
0.176
−1.279
−0.469
−0.666
−0.323
18.50
8.707
5.064

E
mundoserone
−0.425
−1.275
−1.681
0.837
−0.608
17.96
8.461
4.891

E
picropodophyllotoxin
−0.107
−0.952
−2.402
−0.349
−1.202
23.13
11.490
6.009

E
dihydromundulone
0.816
−0.792
0.189
−0.530
0.537
23.53
11.135
5.945

E
podofilox
0.789
−0.716
−1.507
−0.212
−1.436
24.99
12.347
6.311

E
methyl robustone
0.848
−0.638
−0.344
0.715
−0.347
20.15
9.540
5.541

E
robustic acid methyl ether
0.497
−0.589
0.474
0.692
1.431
21.93
11.080
5.749

E
ichthynone
0.234
−0.541
−0.681
−0.325
1.842
19.22
9.346
5.345

E
podophyllotoxin
−0.077
−0.405
−1.865
−0.902
−1.401
23.69
12.039
5.764

E
12a-hydroxy-5-
−0.940
−0.089
−1.976
−0.179
0.823
22.35
10.784
5.999

deoxydehydromunduserone

E
isoduartin methyl ether
−0.603
0.032
−2.055
−0.777
0.599
20.56
10.192
5.414

E
dehydrodihydrorotenone
−0.172
0.084
−3.034
0.125
0.051
19.08
8.887
5.481

E
dihydrosamidin
0.476
0.085
−0.826
0.199
4.794
23.98
11.603
6.477

E
robustic acid
−1.213
0.257
−1.831
−1.086
−0.119
18.87
9.064
5.314

E
8-iodocatechin tetramethyl
0.377
0.343
−1.359
0.146
−0.448
17.34
8.295
4.791

ether

E
duartin(−)
1.175
0.719
−0.571
0.392
0.900
18.71
8.861
5.480

E
rotenonic acid
0.206
0.763
−0.731
0.050
0.173
19.46
9.652
5.304

E
dehydrorotenone
−0.381
0.836
−1.046
0.884
0.804
22.23
10.898
5.629

E
quassin
−0.688
0.866
−0.400
0.033
0.925
20.00
9.699
5.513

E
dihydrorobustic acid
−0.721
2.345
−0.780
0.000
−0.115
18.87
9.266
5.181

TABLE 5

Microtubule modulators in screened collection

ChemBank

ROS

Plate
Well
Compound Name
ID
PubChem_CID
GEHTS_Zscore
Zscore

2160
P17
podofilox
1001531
10607
3.408
−1.436

2160
B22
vinblastine sulfate
3198420
6710780
3.171
−1.327

2162
I04
mebendazole
1350
4030
2.846
−1.003

2164
D21
Nocodazole
440
4122
2.675
−1.099

2166
N05
Podophyllotoxin
1001531
10607
2.561
−1.401

2160
P05
paclitaxel
1000045
441276
2.451
−1.967

2165
A15
Albendazole
1185085
2082
2.379
−1.434

2159
H21
Picropodophyllo-
2069291
72435
2.259
−1.202

toxin

2164
N14
Griseofulvin
3069117
6713927
2.199
0.371

2164
P11
Paclitaxel; taxol
3189060
6713921
2.118
−2.010

2158
O11
Colchicine
1352
6167
1.215
−0.377

2165
I08
Colchicine
1352
6167
0.901
−0.345

2164
L16
Mebendazole
1350
4030
0.623
−0.791

TABLE 6

Sappanone derivatives in screened collection

ChemBank

ROS

Plate
Well
Compound Name
ID
PubChem_CID
GEHTS_Zscore
Zscore

2158
H15
deoxysappanone
2060294
4026888
2.577
−1.712

(B) 7,3′-dimethyl

ether

2164
K15
sappanone (A)
2060467
3288218
2.376
0.1195

trimethyl ether

2163
E21
3-
2060307
6708683
1.970
1.3852

deshydroxysappanol

trimethyl ether

2158
L06
sappanone (A) 7-
3077175
6710767
1.410
−1.493

methyl ether

2158
F15
deoxysappanone
2060494
4643334
0.768
1.064

(B) trimethyl ether

2163
P22
tetrahydrosappanone
2060448
6708784
0.583
0.274

(A) trimethyl

ether

2160
D05
sappanone (A)
2060397
3884104
0.524
−2.429

dimethyl ether

2158
D19
deoxysappanone
3054809
6708755
−0.723
−1.894

(B) 7,3′-dimethyl

ether acetate

TABLE 7

Differential expression of nuclear and mtDNA OXPHOS genes

mito-

nucOXPHOS
OXPHOS

Rank
Compound Name
Z
Rank
Z
Rank

High Nuclear/High Mitochondrial

1
Prieurianin
1.90
12
1.93
14

2
Palmatine
1.64
17
1.83
17

3
vinblastine sulfate
2.09
8
1.64
28

4
anhydrobrazilic acid
1.56
23
1.68
21

5
Minoxidil
2.38
2
1.37
44

6
deoxysappanone b 7,3′-dimethyl
2.25
6
1.38
42

ether

7
Dihydrosamidin
1.84
14
1.48
37

8
Indomethacin
1.32
46
2.40
10

9
Podofilox
2.53
1
1.28
57

10
Fluorouracil
1.50
28
1.55
32

High Nuclear/Low Mitochondrial

1
Emetine
2.31
3
−4.79
12

2
Dihydrocelastrol
2.18
7
−5.22
9

3
Emetine
1.93
10
−4.15
19

4
Crinamine
2.27
5
−2.89
34

5
Lycorine
1.86
13
−3.34
27

6
Cycloheximide
1.35
41
−4.18
17

7
Anisomycin
1.26
52
−3.55
23

8
Lycorine
1.10
74
−5.39
5

9
Cycloheximide
0.69
238
−5.64
3

10
Monensin
0.70
231
−4.13
20

Low Nuclear/High Mitochondrial

1
Perphenazine
−4.32
2
3.42
4

2
Menadione
−3.40
17
2.13
12

3
Chloranil
−2.45
37
2.50
8

4
Triptonide
−2.18
44
5.02
2

5
cetrimonium bromide
−2.70
29
1.66
26

6
Doxorubicin
−1.85
57
2.57
7

7
Puromycin
−2.80
26
1.24
67

8
Daunorubicin
−2.09
49
1.37
45

9
Disulfiram
−4.10
6
0.93
152

10
Thimerosal
−1.20
178
10.41
1

Low Nuclear/Low Mitochondrial

1
Isorotenone
−3.02
21
−4.57
14

2
Neostigmine
−3.54
15
−3.45
24

3
Pararosaniline
−2.25
40
−5.43
4

4
gambogic acid amide
−4.01
10
−2.68
38

5
1-
−4.03
8
−2.48
44

benzyloxycarbonylaminophenethyl

chloromethyl ketone

6
3,4-dimethoxydalbergione
−2.94
22
−2.72
36

7
Pyrromycin
−2.89
23
−2.67
39

8
Perphenazine
−3.10
19
−2.46
45

9
Quinacrine
−2.65
30
−2.81
35

10
pyrvinium pamoate
−2.08
50
−4.40
15

TABLE 8

Summary of glucose uptake after paclitaxel treatment

Treatment Duration
1 nM paclitaxel
p-value
1 μM paclitaxel
p-value

30 minutes
1.11 ± 0.03
0.009
1.19 ± 0.05
0.027

3 hours
1.18 ± 0.05
0.035
1.23 ± 0.19
0.065

Fold change in basal glucose uptake rate compared to DMSO control.

Experiments performed in C2C12 myotubes.

P-values correspond to T-test (two-tailed).

TABLE 9

Tag Sequences and Universal Primers

Tag ID
Tag Sequence
SEQ ID

1
CTTTAATCTCAATCAATACAAATC
SEQ ID NO: 71

2
CTTTATCAATACATACTACAATCA
SEQ ID NO: 72

3
TACACTTTATCAAATCTTACAATC
SEQ ID NO: 73

4
TACATTACCAATAATCTTCAAATC
SEQ ID NO: 74

6
TCAACAATCTTTTACAATCAAATC
SEQ ID NO: 75

7
CAATTCATTTACCAATTTACCAAT
SEQ ID NO 76

8
AATCCTTTTACATTCATTACTTAC
SEQ ID NO: 77

9
TAATCTTCTATATCAACATCTTAC
SEQ ID NO 78

10
ATCATACATACATACAAATCTACA
SEQ ID NO. 79

11
TACAAATCATCAATCACTTTAATC
SEQ ID NO: 80

15
ATACTTCATTCATTCATCAATTCA
SEQ ID NO: 81

18
TCAAAATCTCAAATACTCAAATCA
SEQ ID NO: 82

19
TCAATCAATTAC1TACTCAAATAC
SEQ ID NO: 83

31
TTCACTTTTCAATCAACTTTAATC
SEQ ID NO: 84

32
ATTATTCACTTCAAACTAATCTAC
SEQ ID NO: 85

33
TCAATTACTTCACTTTAATCCTTT
SEQ ID NO: 86

34
TCATTCATATACATACCAATTCAT
SEQ ID NO: 87

35
CAATTTCATCATTCATTCATTTCA
SEQ ID NO: 88

36
CAATTCATTTCATTCACAATCAAT
SEQ ID NO: 89

37
CTTTTCATCTTTTCATCTTTCAAT
SEQ ID NO: 90

38
TCAATCATTACACTTTTCAACAAT
SEQ ID NO: 91

40
CTTTCTACATTATTCACAACATTA
SEQ ID NO: 92

42
CTATCTTCATATTTCACTATAAAC
SEQ ID NO: 93

43
CTTTCAATTACAATACTCATTACA
SEQ ID NO: 94

44
TCATTTACCAATCTTTCTTTATAC
SEQ ID NO: 95

45
TCATTTCACAATTCAATTACTCAA
SEQ ID NO: 96

46
TACATCAACAATTCATTCAATACA
SEQ ID NO: 97

47
CTTCTCATTAACTTACTTCATAAT
SEQ ID NO: 98

48
AAACAAACTTCACATCTCAATAAT
SEQ ID NO: 99

49
TCATCAATCTTTCAATTTACTTAC
SEQ ID NO: 100

50
CAATATACCAATATCATCATTTAC
SEQ ID NO: 101

51
TCATTTCAATCAATCATCAACAAT
SEQ ID NO: 102

52
TCAATCATCTTTATACTTCACAAT
SEQ ID NO: 103

64
CTACATATTCAAATTACTACTTAC
SEQ ID NO: 104

65
CTTTTCATCAATAATCTTACCTTT
SEQ ID NO: 105

ID
Universal Primers

T7
TAATACGACTCACTATAGGG
SEQ ID NO: 106

T3
TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 107

TABLE 10

Probes used in GE-HTS

Gene Name

SEQ ID NO

Upstream primer full sequence (5′-3′)

[T7sequence-Tag-UpstreamTargetSequence]

Mt-Atp6
TAATACGACTCACTATAGGG-CAATTCATTTACCAATTTACCAAT-TTCAAGCCTACGTATTCACC
SEQ ID NO: 108

Mt-Atp8
TAATACGACTCACTATAGGG-TCAATCATTACACTTTTCAACAAT-TCACCAAAATCACTAACAAC
SEQ ID NO: 109

Mt-Co1
TAATACGACTCACTATAGGG-AATCCTTTTACATTCATTACTTAC-CACGACGCTACTCAGACTAC
SEQ ID NO: 110

Mt-Co2
TAATACGACTCACTATAGGG-CTTTCTACATTATTCACAACATTA-AACAAACGACCTAAAACCTG
SEQ ID NO: 111

Mt-Co3
TAATACGACTCACTATAGGG-CTATCTTCATATTTCACTATAAAC-TAGGACTTTACTTCACCATC
SEQ ID NO: 112

Mt-Cytb
TAATACGACTCACTATAGGG-TAATCTTCTATATCAACATCTTAC-CTAATACCTTTCCTTCATAC
SEQ ID NO: 113

Mt-Nd1
TAATACGACTCACTATAGGG-ATCATACATACATACAAATCTACA-TACTACTATCATCAACATTC
SEQ ID NO: 114

Mt-Nd2
TAATACGACTCACTATAGGG-CTTTCAATTACAATACTCATTACA-TTCTTCCTTACAACCCATCC
SEQ ID NO: 115

Mt-Nd3
TAATACGACTCACTATAGGG-TCATTTACCAATCTTTGTTTATAC-TTACATTTCTATTATTTGAC
SEQ ID NO: 116

Mt-Nd4
TAATACGACTCACTATAGGG-TCATTTCACAATTCAATTACTCAA-ACTACGAACGGATCCACAGC
SEQ ID NO: 117

Mt-Nd4I
TAATACGACTCACTATAGGG-TACATCAACAATTCATTCAATACA-ATTATAACTTCAGTAACTTC
SEQ ID NO: 118

Mt-Nd5
TAATACGACTCACTATAGGG-CTTCTCATTAACTTAGTTCATAAT-CCTACTAATTACACTAATCG
SEQ ID NO: 119

Mt-Nd6
TAATACGACTCACTATAGGG-TACAAATCATCAATCACTTTAATC-GAGATTGGTTGATGTATGAG
SEQ ID NO: 120

Atp5a1
TAATACGACTCACTATAGGG-CTTTAATCTCAATCAATACAAATC-AAAGGGTTACTCTTGTATTC
SEQ ID NO: 121

Atp5c1
TAATACGACTCACTATAGGG-CTTTATCAATACATACTACAATCA-CTTGACTTTCAACCGCACCC
SEQ ID NO: 122

Atp5o
TAATACGACTCACTATAGGG-TTCACTTTTCAATCAACTTTAATC-GCTGAAGAGCTTCCTGAGTC
SEQ ID NO: 123

Cox5b
TAATACGACTCACTATAGGG-TACACTTTATCAAATCTTACAATC-CCAAAGGCAGCTTCAGGCAC
SEQ ID NO: 124

Cox7a2
TAATACGACTCACTATAGGG-TCAATTACTTCAGTTTAATCCTTT-CCAATAAAGCAATCCTTAAC
SEQ ID NO: 125

Cyc1
TAATACGACTCAGTATAGGG-ATTATTCACTTCAAACTAATCTAC-TTTCCCGGCCAGGCCATTGG
SEQ ID NO: 126

Hspc051
TAATACGACTCACTATAGGG-TCATTCATATACATACCAATTCAT-TAAGGATGAGTTTCAAGTTG
SEQ ID NO: 127

Ndufa5
TAATACGAGTCACTATAGGG-TACATTACCAATAATCTTCAAATC-TGATATTCTGAAGCACTTTC
SEQ ID NO: 128

Ndufb5
TAATACGACTCACTATAGGG-CAATTTCATCATTCATTCATTTCA-CTGTGCAAGAACAGTGTGTC
SEQ ID NO: 129

Sdhd
TAATACGACTCACTATAGGG-CAATTCATTTCATTCACAATCAAT-TTTAGACAAGTTCAATTTAG
SEQ ID NO: 130

Uqcrb
TAATACGACTCACTATAGGG-CTTTTCATCTTTTCATGTTTCAAT-CTGGATGGTTTTCGAAAGTG
SEQ ID NO: 131

Uqorc1
TAATACGACTCACTATAGGG-TCAACAATCTTTTACAATCAAATC-TCCCAGACTACAACCGGATC
SEQ ID NO: 132

Actb
TAATACGACTCACTATAGGG-AAACAAACTTCACATCTCAATAAT-TAAGTGGTTACAGGAAGTCC
SEQ ID NO: 133

Aamp
TAATACGACTCACTATAGGG-CAATATACCAATATCATCATTTAC-GGGTGCGTCTTTGTATGTTG
SEQ ID NO: 134

Cenpb
TAATACGACTCACTATAGGG-ATACTTCATTCATTCATCAATTCA-GTCCAGCCACCCAGGTGCTC
SEQ ID NO: 135

Eef1a1
TAATACGACTCACTATAGGG-TCAATCAATTACTTACTCAAATAG-ATAACAATGCATCGTAAAAC
SEQ ID NO: 136

Jund
TAATACGACTCACTATAGGG-TCAATCATCTTTATACTTGACAAT-CCGCCTCTCTACCCGGAGTC
SEQ ID NO: 137

Lsp1
TAATACGACTCACTATAGGG-TCATTTCAATCAATCATCAACAAT-TGACCAACGCTCCAACTCTG
SEQ ID NO: 138

Rps2
TAATACGACTCACTATAGGG-TCAAAATCTCAAATACTCAAATCA-ACGGATCATCTTGTGAAAAC
SEQ ID NO: 139

Rps27a
TAATACGACTCACTATAGGG-TCATCAATCTTTGAATTTACTTAC-TGGTAAGCAGCTGGAAGATG
SEQ ID NO: 140

Cyb5r3
TAATACGACTCACTATAGGG-CTTTTCATCAATAATGTTACCTTT-ACTCCATGCAGTCTTGAGTG
SEQ ID NO: 141

EN1
TAATACGACTCACTATAGGG-CTACATATTCAAATTACTACTTAC-TTCTCTGAAACGCAGGATTG
SEQ ID NO: 142

Downstream primer full sequence (5′-3′)

[DownstreamTargetSequence-T3-sequence]

Mt-Atp6
/5Phos/CTCCTAGTAAGCCTATATCT-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 143

Mt-Atp8
/5Phos/CATAAAAGTAAAAACCCCTT-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 144

Mt-Co1
/5Phos/CCAGATGCTTACACCACATG-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 145

Mt-Co2
/5Phos/GTGAACTACGACTGCTAGAA-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 146

Mt-Co3
/5Phos/CTCCAAGCTTCAGAATACTT-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 147

Mt-Cytb
/5Phos/CTCAAAGCAACGAAGCCTAA-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 148

Mt-Nd1
/5Phos/CTATGGATCCGAGCATCTTA-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 149

Mt-Nd2
/5Phos/CTCACTCTACTCAACCTCAT-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 150

Mt-Nd3
/5Phos/CTAGAAATTGCTCTTCTACT-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 151

Mt-Nd4
/5Phos/CGTACTATAATCATGGCCGG-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 152

Mt-Nd4I
/5Phos/GGTAAACTCCAACTCCATAA-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 153

Mt-Nd5
/5Phos/CCACTTCTATAACAGCTATG-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 153

Mt-Nd6
/5Phos/GTTGATGATGTTGGAGTTAT-TGCCTTTAGTGAGGGTTAAT
SEQ ID NO: 154

Atp5a1
/5Phos/CTGATGTACAGAAATCACAT-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 155

Atp5c1
/5Phos/GCCAGGCTGTCATCACAAAG-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 156

Atp5o
/5Phos/CAAACCAAATACTGAAACTG-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 157

Cox5b
/5Phos/CAAGGAAGACCCTAATCTAG-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 158

Upstream primer full sequence (5′-3′)

[T7sequence-Tag-UpstreamTargetSequence]

Cox7a2
/5Phos/CATTTTGTGTCTCCCTTTTC-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 159

Cyc1
/5Phos/CATGGCTCCTCCCATCTACA-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 160

Hspc051
/5Phos/CCGTTCACCGACCGCCAGTG-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 161

Ndufa5
/5Phos/CTAAACATGCAGCCTATAGA-TCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 162

Ndufb5
/5Phos/CCTCTAGTGGGAAGAAATGATCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 163

Sdhd
/5Phos/GGAGTTCTCCTTGTTTGTGGTCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 164

Uqcrb
/5Phos/GTATTATAATGCTGCAGGATTCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 165

Uqrc1
/5Phos/CGCAGTGGCATGTTCTGGCTTCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 166

Actb
/5Phos/CTCACCCTCCCAAAAGCCACTCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 167

Aamp
/5Phos/GGGTTAGGTCTTTGAGGTTCTCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 168

Cenpb
/5Phos/CTTTCCCAGCTTGAATTCAATCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 169

Eef1a1
/5Phos/CTTCAGAAGGAAAGAATGTTTCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 170

Jund
/5Phos/CTGCGCGTGGCTGCCCCTTTTCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 171

Lsp1
/5Phos/CTTCTCACCATCAGCTAAAGTCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 172

Rps2
/5Phos/CCACACCAGAGTCTCTGTTCTCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 173

Rps27a
/5Phos/GCCGGACTTTGTCTGACTACTCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 174

Cyb5r3
/5Phos/CCCTAAGTTGTCAGCCCAACTCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 175

Fhl1
/5Phos/CCTCCTTAACTGTACTCTCCTCCCTTTAGTGAGGGTTAAT
SEQ ID NO: 176

	Number	Date	Country
	60934678	Jun 2007	US
	61066884	Feb 2008	US

Methods and compositions for treating metabolic disorders

Information

Publication Number

Date Filed

Date Published

Inventors

CPC

US Classifications

International Classifications

Abstract

Description

Claims

RELATED APPLICATIONS

Provisional Applications (2)