Claims
- 1. A method to determine the specificity of a drug for a molecular target comprising:;
a) contacting a first cell system expressing the molecular target with a molecular target-specific compound to modulate the function of the molecular target; b) measuring a cellular response of the first cell system to generate a model response; c) contacting a second cell system substantially similar to the first cell system with a drug intended to modulate the function of the molecular target; d) measuring a cellular response of the second cell system to generate a drug response; e) comparing the model response with the drug response, whereby the specificity of the drug for the molecular target is determined.
- 2. The method of claim 1, wherein the drug is a combination of more than one drug.
- 3. The method of claim 1 wherein the target-specific compound is an antisense reagent.
- 4. The method of claim 3, wherein the target-specific compound further comprises a target-specific compound selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 5. The method of claim 1, wherein the target-specific compound is selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 6. The method of claim 1, wherein measuring the cellular response comprises detecting a change selected from the group consisting of a change in cell phenotype, a change in the transcriptome, a change in metabolome, and a change in the proteome.
- 7. The method of claim 1, where in specificity is determined by the equation Per Cent Specificity=100%×(M)/(C).
- 8. A method to identify a drug with a higher specificity for a molecular target, comprising:
a) performing the method of claim 1 independently for more than one drug, and b) comparing the specificity of at least two drugs, whereby the drug having the higher specificity for the molecular target is identified.
- 9. A method to identify a non-target effect of a drug for a molecular target comprising:
a) contacting a first cell system expressing the molecular target with a molecular target-specific compound to modulate the function of the molecular target; b) measuring a cellular response of the first cell system to generate a model response; c) contacting a second cell system substantially similar to the first cell system with a drug intended to modulate the function of the molecular target; d) measuring a cellular response of the second cell system to generate a drug response; e) comparing the model response to the drug response to detect a difference between the model response and the drug response, whereby a non-target effect of the drug may be identified.
- 10. The method of claim 9, wherein the drug is a combination of more than one drug.
- 11. The method of claim 9 wherein the target-specific compound is an antisense reagent.
- 12. The method of claim 11, wherein the target-specific compound further comprises a target-specific compound selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 13. The method of claim 9, wherein the target-specific compound is selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 14. The method of claim 9, wherein measuring the cellular response comprises detecting a change selected from the group consisting of a change in cell phenotype, a change in the transcriptome, a change in metabolome, and a change in the proteome.
- 15. The method of claim 9, wherein non-target drug effects are determined by the equation Non-target drug effects=C−M.
- 16. A method to identify a non-target effect of a drug for a molecular target comprising:
a) contacting a first cell system not expressing the molecular target with a molecular target-specific compound to modulate the function of the molecular target; b) measuring a cellular response of the first cell system to generate a model response; c) contacting a second cell system substantially similar to the first cell system with a drug intended to modulate the function of the molecular target; d) measuring a cellular response of the second cell system to generate a drug response; e) comparing the model response to the drug response to detect a difference between the model response and the drug response, whereby a non-target effect of the drug may be identified.
- 17. The method of claim 16, wherein the drug is a combination of more than one drug.
- 18. The method of claim 16, wherein the target-specific compound is an antisense reagent.
- 19. The method of claim 18, wherein the target-specific compound further comprises a target-specific compound selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 20. The method of claim 16, wherein the target-specific compound is selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 21. The method of claim 16, wherein measuring the cellular response comprises detecting a change selected from the group consisting of a change in cell phenotype, a change in the transcriptome, a change in metabolome, and a change in the proteome.
- 22. The method of claim 16, wherein non-target drug effects are determined by the equation Non-target drug effects=C−M.
- 23. A method to identify a non-target effect of a drug for a molecular target comprising:
a) contacting a first cell system expressing the molecular target with a molecular target-specific compound and a drug to modulate the function of the molecular target; b) measuring a cellular response of the first cell system to generate a combined response; c) contacting a second cell system substantially similar to the first cell system with a target-specific agent intended to modulate the function of the molecular target; d) measuring a cellular response of the second cell system to generate a model response; e) comparing the combined response to the model response to detect a difference between the model response and the drug response, whereby a non-target effect of the drug may be identified.
- 24. The method of claim 23, wherein the drug is a combination of more than one drug.
- 25. The method of claim 23, wherein the target-specific compound is an antisense reagent.
- 26. The method of claim 25, wherein the target-specific compound further comprises a target-specific compound selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 27. The method of claim 23, wherein the target-specific compound is selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 28. The method of claim 23, wherein measuring the cellular response comprises detecting a change selected from the group consisting of a change in cell phenotype, a change in the transcriptome, a change in metabolome, and a change in the proteome.
- 29. The method of claim 23, wherein non-target drug effects are determined by the equation Non-target drug effects=C−M.
- 30. A method to identify a molecular target whose function may be modulated to produce a desired biological effect comprising:
a) contacting a first cell system expressing a molecular target with a molecular target-specific compound capable of producing the desired biological effect; b) measuring a cellular response of the first cell system to generate a model response; c) contacting a second cell system expressing a second molecular target with a molecular target-specific compound to modulate the function of the second molecular target; d) measuring a cellular response of the second cell system; e) comparing the model response to the cellular response to detect molecular targets whose function has been modulated, whereby molecular targets whose function may be modulated to produce a desired biological effect may be identified.
- 31. The method of claim 30, wherein the drug is a combination of more than one drug.
- 32. The method of claim 30, wherein the target-specific compound is an antisense reagent.
- 33. The method of claim 32, wherein the target-specific compound further comprises a target-specific compound selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 34. The method of claim 30, wherein the target-specific compound is selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 35. The method of claim 30, wherein measuring the cellular response comprises detecting a change selected from the group consisting of a change in cell phenotype, a change in the transcriptome, a change in metabolome, and a change in the proteome.
- 36. A method to refine the determination of drug specificity for a protein molecular target comprising:
a) contacting a first cell system expressing the molecular target homolog with a molecular target-specific compound to modulate the function of the molecular target, wherein the function of the homolog is modulated by less than about 50%; b) measuring a cellular response of the first cell system to generate a model response; c) contacting a second cell system substantially similar to the first cell system with a drug suspected of modulating the function of the molecular target; d) measuring a cellular response of the second cell system to generate a drug response; e) comparing the model response with the drug response, whereby the determination of drug specificity may be refined.
- 37. The method of claim 36, wherein the drug is a combination of more than one drug.
- 38. The method of claim 36, wherein the target-specific compound is an antisense reagent.
- 39. The method of claim 38, wherein the target-specific compound further comprises a target-specific compound selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 40. The method of claim 36, wherein the target-specific compound is selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 41. The method of claim 36, wherein measuring the cellular response comprises detecting a change selected from the group consisting of a change in cell phenotype, a change in the transcriptome, a change in metabolome, and a change in the proteome.
- 42. A method to determine differences in drug response of different cell systems comprising:
a) contacting a first cell system expressing the molecular target with a molecular target-specific compound to modulate the function of the molecular target; b) measuring a cellular response of the first cell system to generate a model response; c) contacting a second cell system with a drug suspected of modulating the function of the molecular target; d) measuring a cellular response of the second cell system to generate a drug response; e) comparing the model response with the drug response to determine a difference in a cell system-specific response for the intended molecular target, whereby a difference in a drug response is determined.
- 43. The method of claim 42, wherein the drug is a combination of more than one drug.
- 44. The method of claim 42, wherein the first and second cell systems are derived from different species.
- 45. The method of claim 42, wherein the first cell system expressing the molecular target expresses a species-specific homolog of the molecular target.
- 46. The method of claim 42, wherein the target-specific compound is an antisense reagent.
- 47. The method of claim 46, wherein the target-specific compound further comprises a target-specific compound selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 48. The method of claim 42, wherein the target-specific compound is selected from the group consisting of an aptamer, an antibody, a drug, a ribozyme, a zinc finger binding protein, an RNA editing protein, an siRNA, and a chimeraplast.
- 49. The method of claim 42, wherein measuring the cellular response comprises detecting a change selected from the group consisting of a change in cell phenotype, a change in the transcriptome, a change in metabolome, and a change in the proteome.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application No. 60/287,759, “Methods for identifying Drugs Specific for Known Molecular Targets Using Antisense Reagents as Model Inhibitors,” filed May 1, 2001, which is incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60287759 |
May 2001 |
US |