Protein kinase inhibitors and methods for identifying same
View Patent ↗Inhibitors of protein kinase C (PKC)α, PKCδ and PKCζ are provided which are selective for those PKC isotypes. Combinatorial libraries for identifying protein kinases are also provided, as are methods of identifying protein kinases using those libraries. Additionally, methods of treating a mammal having a deleterious condition, where the condition is dependent on a protein kinase for induction or severity, are provided. Methods of inhibiting protein kinases are also provided.
1. An inhibitor of a protein kinase Cα (PKCα), the inhibitor comprising
A-Ala-Arg-Arg-X-B-Hyd-C-D- (SEQ ID NO:1), where A=AcHN—,
X=any amino acid; B=Ala or a diaminopropionic acid (Dap) derivative having the formula
Hyd=Phe, Leu or Ile; C=Ara or Lys: and D=Ala or a Dap derivative having the formula
2. The inhibitor of claim 1 , wherein the PKCα is a human PKCα.
3. An inhibitor of a protein kinase Cα (PKCα), the inhibitor comprising
4. The inhibitor of claim 1 , having an IC 50 <50 μM for the PKCα.
5. The inhibitor of claim 1 , having an IC 50 <10 μM for the PKCα.
6. The inhibitor of claim 1 , having an IC 50 <1 μM for the PKCα.
7. The inhibitor of claim 1 , wherein the inhibitor has an IC 50 for the PKCα<0.1 that of any other PKC isoform.
8. The inhibitor of claim 1 , wherein the inhibitor has an IC 50 for the PKCα<0.01 that of any other PKC isoform.
9. The inhibitor of claim 3 , comprising
10. The inhibitor of claim 3 , consisting of
11. The inhibitor of claim 3 , comprising
12. The inhibitor of claim 3 , consisting of
13. The inhibitor of claim 1 , comprising
14. The inhibitor of claim 1 , consisting of
15. The inhibitor of claim 1 , comprising
16. The inhibitor of claim 1 , consisting of
17. The inhibitor of claim 1 , comprising
18. The inhibitor of claim 1 , consisting of
19. The inhibitor of claim 1 , comprising
20. The inhibitor of claim 1 , consisting of