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 X 1 X 2 PSLSIDX 9 PX 11 X 12 LLRTLLELEKTQSQRERAEQNAX 35 IFAX 39 V (SEQ ID NO: 531)
wherein:
X 1 is selected from nil and D;
X 2 is selected from nil and N;
X 9 is selected from L and V;
X 11 is selected from L, and F;
X 12 is selected from L, F, and Y;
X 35 is selected from R, H, and Q;
X 39 is selected from H and R;
and variants thereof having at least about 95% sequence identity to said peptide.
2. The peptide according to claim 1 , wherein X 1 X 2 are selected from the group consisting of DN.
3. The peptide according to claim 1 , wherein X 11 X 12 are selected from the group consisting of LL, LF, FF, and LY.
4. The peptide according to claim 2 , wherein X 11 X 12 are selected from the group consisting of LL, LF, FF, and LY.
5. The peptide according to claim 1 , wherein X 9 is.
6. The peptide according to claim 1 , wherein X 35 is.
7. The peptide according to claim 1 , wherein X 39 is.
8. The peptide according to claim 1 , wherein the peptide comprises a sequence selected from the group consisting of SEQ ID NO: 324, 328, 331, 333, 334, 341, 384, 385, 386, and 387.
9. 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 .
10. The method according to claim 9 , wherein the CRF 2 R modulated disorder is skeletal muscle atrophy or a form of muscular dystrophy.
11. A pharmaceutical composition comprising:
a. a safe and effective amount of a peptide of claim 1 ; and
b. a pharmaceutically acceptable carrier.
12. 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.
13. 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 8 .
14. The method according to claim 13 , wherein the CRF 2 R modulated disorder is skeletal muscle atrophy or muscular dystrophy.
15. A pharmaceutical composition comprising:
a. a safe and effective amount of a peptide of claim 8 ; and
b. a pharmaceutically acceptable carrier.
16. A kit for preventing or treating a CRF 2 R modulated disorder comprising:
a. a peptide of claim 8 in a unit dose form; and
b. usage instruction.
17. A variant according to claim 1 , having at least about 97% sequence identity to said peptide.
18. A non-native peptide comprising the sequence of SEQ ID NO: 341, and variants thereof having at least about 95% sequence identity to said peptide.
19. A variant according to claim 18 , having at least about 97% sequence identity to said peptide.
20. 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 18 .
21. The method according to claim 20 , wherein the CRF 2 R modulated disorder is skeletal muscle atrophy or muscular dystrophy.
22. A pharmaceutical composition comprising:
a. a safe and effective amount of a peptide of claim 18 ; and
b. a pharmaceutically acceptable carrier.
23. A non-native peptide comprising the sequence of SEQ ID NO: 341.
24. 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 23 .
25. The method according to claim 24 , wherein the CRF 2 R modulated disorder is skeletal muscle atrophy or muscular dystrophy.
26. A pharmaceutical composition comprising:
a. a safe and effective amount of a peptide of claim 23 ; and
b. a pharmaceutically acceptable carrier.
27. A non-native peptide comprising the sequence:
X 1 X 2 PSLSIDX 9 PX 11 X 12 LLRTLLELEKTQSQRERAEQNAX 35 IFAX 39 V (SEQ ID NO: 531)
wherein:
X 1 is selected from nil and D;
X 2 is selected from nil and N;
X 9 is selected from L and V;
X 11 is selected from L, and F;
X 12 is selected from L, F, and Y;
X 35 is selected from R, H, and Q;
X 39 is selected from H and R.
28. 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 27 .
29. The method according to claim 28 , wherein the CRF 2 R modulated disorder is skeletal muscle atrophy or muscular dystrophy.
30. A pharmaceutical composition comprising:
a. a safe and effective amount of a peptide of claim 27 ; and
b. a pharmaceutically acceptable carrier.