Method and compounds for inhibition of cell death
View Patent ↗The invention is directed to methods and compositions for inhibiting caspase-independent apoptosis. In particular, methods and compositions for inhibiting Omi/HtrA2 activity, as well as method for identifying other inhibitors of Omi/HtrA2. Also disclosed are Omi/HtrA2 specific substrates and methods for identifying other substrates of Omi/HtrA2.
1. A pharmaceutical composition for inhibiting cellular apoptosis, the composition comprising at least one apoptosis inhibiting compound that can modulate caspase-independent apoptosis and a pharmaceutically acceptable carrier, wherein the apoptosis inhibiting compound has the structure:
wherein R1 is selected from the group consisting of a nitro group, a carboxy group, a hydroxide, an aliphatic group, an aromatic group, an acyl group, an alkoxy group, an alkeylene group, an alkenylene group, an alkynylene group, a hydroxycarbonylalkyl group, an anhydride, an amide, an amine, and a heterocyclic aromatic group.
2. The pharmaceutical composition of claim 1 further comprising a pharmaceutical acceptable excipient.
3. The pharmaceutical composition of claim 1 , wherein the apoptosis inhibiting compound is
4. A pharmaceutical composition, for inhibiting cellular apoptosis, the composition comprising at least one apoptosis inhibiting compound that can modulate caspase-independent apoptosis and a pharmaceutically acceptable carrier, wherein the apoptosis inhibiting compound has the structure:
wherein R1 is selected from the group consisting of a nitro group, a carboxy group, a hydroxide, an aliphatic group, an aromatic group, an acyl group, an alkoxy group, an alkeylene group, an alkenylene group, an alkynylene group, a hydroxycarbonylalkyl group, an anhydride, an amide, an amine, and a heterocyclic aromatic group, an wherein R2 is a methoxy group.
5. The pharmaceutical composition of claim 4 , wherein the apoptosis inhibiting compound is
6. A pharmaceutical composition for inhibiting cellular apoptosis, the composition comprising at least one apoptosis inhibiting compound that can modulate caspase-independent apoptosis and a pharmaceutically acceptable carrier, wherein the apoptosis inhibiting compound has the structure:
wherein R1 is selected from the group consisting of a nitro group, a carboxy group, a hydroxide, an aliphatic group, an aromatic group, an acyl group, an alkoxy group, an alkeylene group, an alkenylene group, an alkynylene group, a hydroxycarbonylalkyl group, an anhydride, an amide, an amine, and a heterocyclic aromatic group.
7. The pharmaceutical composition of claim 6 , wherein the apoptosis inhibiting compound is
8. A pharmaceutical composition for inhibiting cellular apoptosis, the composition comprising at least one apoptosis inhibiting compound that can modulate caspase-independent apoptosis and a pharmaceutically acceptable carrier, wherein the apoptosis inhibiting compound has the structure:
wherein R1 is selected from the group consisting of a nitro group, a carboxy group, a hydroxide, an aliphatic group, an aromatic group, an acyl group, an alkoxy group, an alkeylene group, an alkenylene group, an alkynylene group, a hydroxycarbonylalkyl group, an anhydride, an amide, an amine, and a heterocyclic aromatic group.
9. The pharmaceutical composition of claim 8 , wherein the apoptosis inhibiting compound is
10. The pharmaceutical composition of claim 1 , wherein the apoptosis inhibiting compound alters a functional activity of Omi/HtrA2.
11. The pharmaceutical composition of claim 1 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 proteolytic activity.
12. The pharmaceutical composition of claim 1 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 activity at least about 20% to about 90%.
13. The pharmaceutical composition of claim 3 , wherein the apoptosis inhibiting compound alters a functional activity of Omi/HtrA2.
14. The pharmaceutical composition of claim 4 , wherein the apoptosis inhibiting compound alters a functional activity of Omi/HtrA2.
15. The pharmaceutical composition of claim 5 , wherein the apoptosis inhibiting compound alters a functional activity of Omi/HtrA2.
16. The pharmaceutical composition of claim 6 , wherein the apoptosis inhibiting compound alters a functional activity of Omi/HtrA2.
17. The pharmaceutical composition of claim 7 , wherein the apoptosis inhibiting compound alters a functional activity of Omi/HtrA2.
18. The pharmaceutical composition of claim 8 , wherein the apoptosis inhibiting compound alters a functional activity of Omi/HtrA2.
19. The pharmaceutical composition of claim 9 , wherein the apoptosis inhibiting compound alters a functional activity of Omi/HtrA2.
20. The pharmaceutical composition of claim 3 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 proteolytic activity.
21. The pharmaceutical composition of claim 4 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 proteolytic activity.
22. The pharmaceutical composition of claim 5 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 proteolytic activity.
23. The pharmaceutical composition of claim 6 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 proteolytic activity.
24. The pharmaceutical composition of claim 7 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 proteolytic activity.
25. The pharmaceutical composition of claim 8 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 proteolytic activity.
26. The pharmaceutical composition of claim 9 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 proteolytic activity.
27. The pharmaceutical composition of claim 3 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 activity at least about 20% to about 90%.
28. The pharmaceutical composition of claim 4 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 activity at least about 20% to about 90%.
29. The pharmaceutical composition of claim 5 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 activity at least about 20% to about 90%.
30. The pharmaceutical composition of claim 6 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 activity at least about 20% to about 90%.
31. The pharmaceutical composition of claim 7 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 activity at least about 20% to about 90%.
32. The pharmaceutical composition of claim 8 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 activity at least about 20% to about 90%.
33. The pharmaceutical composition of claim 9 , wherein the apoptosis inhibiting compound inhibits Omi/HtrA2 activity at least about 20% to about 90%.
34. A pharmaceutical composition for inhibiting cellular apoptosis, the composition comprising at least two apoptosis inhibiting compounds that can modulate caspase-independent apoptosis and a pharmaceutically acceptable carrier, wherein the apoptosis inhibiting compounds are