Corticotropin releasing factor 2 receptor agonists
View Patent ↗Isolated corticotropin releasing factor derivatives, and nucleic acids encoding the same, are effective for treating corticotropin releasing factor 2 receptor modulated disorders such as muscular dystrophy.
1. A non-native peptide comprising the sequence ZGPPISIDLPX 11 X 12 LLRKX 17 IEIEKQEKEKQQAX 31 X 32 NAX 35 X 36 X 38 X 39 X 40 (SEQ ID NO: 531)
wherein:
X 11 is selected from F, Y, L, I, and T;
X 12 is selected from Q, W, and Y;
X 17 is selected from V and M;
X 31 is selected from T and A;
X 32 is selected from N and T;
X 35 is selected from R and L;
X 36 is selected from L and I;
X 38 is selected from D and A;
X 39 is selected from T and R;
X 40 is selected from I and V;
and variants thereof having at least about 95% sequence identity to said peptide.
2. The peptide according to claim 1 , wherein X 11 is selected from F, L, T, and Y.
3. The peptide according to claim 1 , wherein X 11 X 12 are selected from the group consisting of FQ, YQ, YW, LQ, LY, IY, and TY.
4. The peptide according to claim 1 , wherein X 31 X 32 are selected from the group consisting of AN, and TT.
5. The peptide according to claim 1 , wherein X 35 X 36 are selected from the group consisting of RL, LL, and RI.
6. The peptide according to claim 1 , wherein X 38 X 39 X 40 are selected from the group consisting of DTI, ARI, ATI, DRV, and ARV.
7. The peptide according to claim 3 , wherein X 31 X 32 are selected from the group consisting of AN, and TT.
8. The peptide according to claim 3 , wherein X 35 X 36 are selected from the group consisting of RL, LL, and RI.
9. The peptide according to claim 3 , wherein X 38 X 39 X 40 are selected from the group consisting of DTI, ARI, ATI, DRV, and ARV.
10. The peptide according to claim 4 , wherein X 35 X 36 are selected from the group consisting of RL, LL, and RI.
11. The peptide according to claim 4 , wherein X 38 X 39 X 40 are selected from the group consisting of DTI, ARI, ATI, DRV, and ARV.
12. The peptide according to claim 5 , wherein X 38 X 39 X 40 are selected from the group consisting of DTI, ARI, ATI, DRV, and ARV.
13. The peptide according to claim 7 , wherein X 35 X 36 are selected from the group consisting of RL, LL, and RI.
14. The peptide according to claim 7 , wherein X 38 X 39 X 40 are selected from the group consisting of DTI, ARI, ATI, DRV, and ARV.
15. The peptide according to claim 10 , wherein X 38 X 39 X 40 are selected from the group consisting of DTI, ART, ATI, DRV, and ARV.
16. The peptide according to claim 1 , wherein the peptide comprises a sequence selected from the group consisting of SEQ ID NO: 22, 144, 148, 149, 151, 278, 279, 286, 288, 311, 349, 350, 351, 352, and 353.
17. A method of preventing or treating a CRF 2 R modulated disorder comprising administering to a host in need of such treatment a safe and effective amount of a peptide of claim 1 .
18. The method according to claim 17 , wherein the CRF 2 R modulated disorder is skeletal muscle atrophy or muscular dystrophy.
19. A pharmaceutical composition comprising:
a. a safe and effective amount of a peptide of claim 1 ; and
b. a pharmaceutically acceptable carrier.
20. A kit for preventing or treating a CRF 2 R modulated disorder comprising:
a. a peptide of claim 1 in a unit dose form; and
b. usage instruction.
21. A method of preventing or treating a CRF 2 R modulated disorder comprising administering to a host in need of such treatment a safe and effective amount of a peptide of claim 16 .
22. The method according to claim 21 , wherein the CRF 2 R modulated disorder is skeletal muscle atrophy or muscular dystrophy.
23. A pharmaceutical composition comprising:
a. a safe and effective amount of a peptide of claim 16 ; and
b. a pharmaceutically acceptable carrier.
24. A variant according to claim 1 , having at least about 97% sequence identity to said peptide.
25. A non-native peptide comprising the sequence of SEQ ID NO: 278, and variants thereof having at least about 95% sequence identity to said peptide.
26. A variant according to claim 25 , having at least about 97% sequence identity to said peptide.
27. A method of preventing or treating a CRF 2 R modulated disorder comprising administering to a host in need of such treatment a safe and effective amount of a peptide of claim 25 .
28. The method according to claim 27 , wherein the CRF 2 R modulated disorder is skeletal muscle atrophy or muscular dystrophy.
29. A pharmaceutical composition comprising:
a. a safe and effective amount of a peptide of claim 25 ; and
b. a pharmaceutically acceptable carrier.
30. A non-native peptide comprising the sequence of SEQ ID NO: 278.
31. A method of preventing or treating a CRF 2 R modulated disorder comprising administering to a host in need of such treatment a safe and effective amount of a peptide of claim 30 .
32. The method according to claim 31 , wherein the CRF 2 R modulated disorder is skeletal muscle atrophy or muscular dystrophy.
33. A pharmaceutical composition comprising:
a. a safe and effective amount of a peptide of claim 30 ; and
b. a pharmaceutically acceptable carrier.
34. A non-native peptide comprising the sequence ZGPPISIDLPX 11 X 12 LLRKX 17 IEIEKQEKEKQQAX 31 X 32 NAX 35 X 36 LX 38 X 39 X 40 (SEQ ID NO: 531)
wherein:
X 11 is selected from F, Y, L, I, and T;
X 12 is selected from Q, W, and Y;
X 17 is selected from V and M;
X 31 is selected from T and A;
X 32 is selected from N and T;
X 35 is selected from R and L;
X 36 is selected from L and I;
X 38 is selected from D and A;
X 39 is selected from T and R;
X 40 is selected from I and V.
35. A method of preventing or treating a CRF 2 R modulated disorder comprising administering to a host in need of such treatment a safe and effective amount of a peptide of claim 34 .
36. The method according to claim 35 , wherein the CRF 2 R modulated disorder is skeletal muscle atrophy or muscular dystrophy.
37. A pharmaceutical composition comprising:
a. a safe and effective amount of a peptide of claim 34 ; and
b. a pharmaceutically acceptable carrier.