Peptides and compounds that bind to a receptor
AssigneeOrtho-McNeil Pharmaceutical, Inc.
InventorsBrian MacDonald, Jeffery Weis, Edward Yurkow
Life of this patent
Estimating the term…
Abstract
Peptides and compounds that bind to and activate the thrombopoietin receptor (c-mpl or TPO-R) or otherwise act as a TPO agonist are disclosed.
Claims49
A compound that binds to a thrombopoietin receptor, wherein said compound comprises (H-IEGPTLRQ(2-Nal)LAARX10)2K-NH2, wherein X10 is selected from the group consisting of sarcosine or β-alanine.
A method of activating a thrombopoietin receptor in a cell, comprising contacting said cell with an effective amount of a compound which comprises (H-IEGPTLRQ(2-Nal)LAARX10)2K-NH2, wherein X10 is selected from the group consisting of sarcosine or β-alanine.
A method of treating a patient suffering from thrombocytopenia, comprising administering to said patient a therapeutically effective dose of a compound which comprises (H-IEGPTLRQ(2-Nal)LAARX10)2K-NH2, wherein X10 is selected from the group consisting of sarcosine or β-alanine.
A method of prophylactically treating a patient at risk of thrombocytopenia, comprising administering to said patient a prophylactically effective amount of a compound which comprises (H-IEGPTLRQ(2-Nal)LAARX10)2K-NH2, wherein X10 is selected from the group consisting of sarcosine or β-alanine.
A compound that binds to thrombopoietin receptor, said compound having:
- (1) a molecular weight of less than about 8000 daltons, and
- (2) a binding affinity to thrombopoietin receptor as expressed by an IC50 of no more than about 100 μM, wherein said compound comprises the following sequence of amino acids:
- X9 X8 G X1 X2 X3 X4 X5 X6 X7
- where X9 is A, C, E, G, I, L, M, P, R, Q, S, T, or V;
- X8 is A, C, D, E, K, L, Q, R, S, T, or V, X1 is C, L, M, P, Q, V;
- X2 is F, K, L, N, Q, R, S, T or V;
- X3 is C, F, I, L, M, R, S, V or W;
- X4 is any of the 20 genetically coded L-amino acids;
- X5 is A, D, E, G, K, M, Q, R, S, T, V or Y;
- X7 is C, G, I, K, L, M, N, R or V, and X6 is β-(2-naphthyl)alanine.
1. A method of activating a thrombopoietin receptor in a cell, comprising contacting said cell with an effective amount of a peptide having a molecular weight of less than about 8000 daltons, said compound comprises the following sequence of amino acids:
- X9 X8 G X1 X2 X3 X4 X5 X6 X7
- where X9 is A, C, E, G, I, L, M, P, R, Q, S, T, or V;
- X8 is A, C, D, E, K, L, Q, R, S, T, or V, X1 is C, L, M, P, Q, V;
- X2 is F, K, L, N, Q, R, S, T or V;
- X3 is C, F, I, L, M, R, S, V or W;
- X4 is any of the 20 genetically coded L-amino acids;
- X5 is A, D, E, G, K, M, Q, R, S, T, V or Y;
- X7 is C, G, I, K, L, M, N, R or V, and X6 is β-(2-naphthyl)alanine.
A method of activating a thrombopoietin receptor in a cell, comprising contacting said cell with an effective amount of a compound covalently attached to a hydrophilic polymer, said compound comprises the amino acid sequence I E G P T L R Q (2-Nal) L A A R A.
Dependencies are inferred from the claim text.