Claims
- 1. An isolated agent comprising a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through. 55, wherein said agent derepresses an IAP-inhibited caspase.
- 2. An isolated agent comprising a core structure selected from any of the structures shown in FIG. 5, any of the structures shown in FIG. 9, any of the structures shown in FIG. 10, and any of the structures shown in FIG. 14B, wherein said agent derepresses an IAP-inhibited caspase.
- 3. The agent of claim 1 or 2, wherein said agent derepresses an XIAP-inhibited caspase.
- 4. The agent of claim 1 or 2, wherein said agent derepresses an XIAP-inhibited caspase-3.
- 5. A pharmaceutical composition comprising the agent of claim 1 or 2 and a pharmaceutically acceptable carrier.
- 6. A complex comprising an IAP bound to an agent selected from the group consisting of a core peptide having a sequence set forth in any of Core peptides 4 through 39 and 42 through 55, and an agent having a core structure selected from the group consisting of TPI759, TPI882, TPI914 or TPI927.
- 7. The complex of claim 6, wherein said IAP is selected from the group consisting of XIAP, c-IAP-1, c-IAP-2, and survivin.
- 8. A method of derepressing an IAP-inhibited caspase, comprising contacting an IAP-inhibited caspase with an effective amount of an agent to derepress an IAP-inhibited caspase, said agent having a core motif selected from the group consisting of a core peptide having a sequence set forth in any of Core peptides 4 through 39 and 42 through 55, and a core structure selected from the group consisting of TPI759, TPI882, TPI914 or TPI927.
- 9. The method of claim 8, wherein said IAP is selected from the group consisting of XIAP, c-IAP-1, c-IAP-2, and survivin.
- 10. The method of claim 8, wherein said caspase is selected from the group consisting of caspase-3, caspase-7 and caspase-9.
- 11. The method of claim 8, wherein said contacting is performed in vitro.
- 12. The method of claim 8, wherein said contacting occurs in a cell.
- 13. A method of promoting apoptosis in a cell, comprising contacting a cell with an effective amount of an agent to derepress an IAP-inhibited caspase, said agent having a core motif selected from the group consisting of a core peptide having a sequence set forth in any of Core peptides 4 through 39 and 42 through 55, and a core structure selected from the group consisting of TPI759, TPI882, TPI914 or TPI927.
- 14. The method of claim 13, wherein said cell is a eukaryotic cell.
- 15. The method of claim 13, wherein said IAP is selected from the group consisting of XIAP, c-IAP-1, c-IAP-2 and survivin.
- 16. The method of claim 13, wherein said caspase is selected from the group consisting of caspase-3, caspase-7 and caspase-9.
- 17. A method of reducing the severity of a pathologic condition in an individual, comprising administering to an individual having a pathologic condition characterized by a pathologically reduced level of apoptosis, an effective amount of an agent to derepress an IAP-inhibited caspase, said agent having a core motif selected from the group consisting of a core peptide having a sequence set forth in any of Core peptides 4 through 39 and 42 through 55, and a core structure selected from the group consisting of TPI759, TPI882, TPI914 or TPI927.
- 18. The method of claim 17, wherein said pathologic condition is cancer.
- 19. The method of claim 17, wherein said pathologic condition is selected from the group consisting of psoriasis, hyperplasia, an autoimmune disease and restenosis.
- 20. The method of claim 17, wherein said IAP is selected from the group consisting of XIAP, c-IAP-1, c-IAP-2 and survivin.
- 21. The method of claim 17, wherein said caspase is selected from the group consisting of caspase-3, caspase-7 and caspase-9.
- 22. A method of identifying an agent that derepresses an IAP-inhibited caspase, comprising:
(a) detecting a labeled derepressor of an IAP-inhibited caspase bound to an IAP or caspase, said labeled derepressor of an IAP-inhibited caspase comprising a core motif selected from a core sequence set forth in any of Core peptides 4 through 39 and 42 through 55, or a core structure selected from the group consisting of TPI759, TPI882, TPI914 and TPI927; (b) contacting the bound IAP or caspase with a candidate agent, said candidate agent suspected of being able to derepress an IAP-inhibited caspase; and (c) detecting dissociation of said labeled derepressor of an IAP-inhibited caspase from said IAP or caspase, whereby said candidate agent is identified as an agent that derepresses an IAP-inhibited caspase.
- 23. The method of claim 22, wherein the IAP is selected from the group consisting of XIAP, c-IAP-1, c-IAP-2, and survivin.
- 24. The method of claim 22, wherein said IAP-inhibited caspase is selected from the group consisting of caspase-3, caspase-7 and caspase-9.
- 25. The method of claim 22, wherein said contacting is performed in vitro.
- 26. The method of claim 22, wherein said contacting occurs in a cell.
Parent Case Info
[0001] This application claims benefit of the filing date of U.S. Provisional Application No. 60/331,957, filed Nov. 21, 2001, and which is incorporated herein by reference.
Government Interests
[0002] This invention was made with government support under grant number CA78040 awarded by The National Institute of Health/National Cancer Institute. The United States Government has certain rights in this invention.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60331957 |
Nov 2001 |
US |