Compounds that bind to the erythropoietin receptor

摘要

The present invention provides mimetics of erythropoietin that bind to the erythropoietin receptor and that are suitable for use in pharmaceutical compositions. The present invention also provides methods of treatment using the mimetics of erythropoietin as well as methods of making the mimetics of erythropoietin.

主权项

1. An erythropoietin (EPO) mimetic comprising a first chain, a second chain and a linker wherein at least one of the first and second chains comprises:
a. a loop, wherein the loop comprises a sequence selected from the group consisting of R-M-G-W-V (SEQ ID NO: 1); R-M-βA-W-V (SEQ ID NO: 2); R-M-F-W-V (SEQ ID NO: 3); R-M-homoF-W-V (SEQ ID NO: 4); R-M-L-W-V (SEQ ID NO: 5); R-M-nL-W-V (SEQ ID NO: 6); R-M-P-W-V (SEQ ID NO: 7); H-M-P-W-V (SEQ ID NO: 8); R-M-P-Nal-V (SEQ ID NO: 9); H-M-P-Nal-V (SEQ ID NO: 10); and R-M-P-X-V (SEQ ID NO: 11): and b. a bridge, wherein:
i. the bridge comprises a series of between about three to about seven bonds, andii. the bridge is covalently linked across the loop; and wherein the linker is covalently bound to each of the first and second chains at sequence positions of, independently, from between about residue 5 to about residue 18.