Insulin receptor partial agonists
View Patent ↗Insulin dimers and insulin analog dimers that act as partial agonists at the insulin receptor are disclosed.
1. A compound selected from the group consisting of
wherein the disulfide linkages between the Cys 6 and Cys 11 residues of the A-chain polypeptide and the disulfide linkages between the Cys 7 and Cys 20 of the A-chain to the Cys 7 and Cys 19 of the B-chain polypeptide, respectively, are represented by the solid line therebetween; wherein the linking moieties are covalently linked to the epsilon amino acid of the shown lysine residue, wherein the A-chain polypeptide for Dimers 13, 18, 19, 20, 24, 28, 32, 54, 55, 56, 58, 65, and 83 has the amino acid sequence shown in SEQ ID NO:1; the B-chain polypeptide for Dimers 13, 24, 54, 55, 56, and 58 has the amino acid sequence shown in SEQ ID NO:2; the B-chain polypeptide for Dimers 18 and 32 has the amino acid sequence shown in SEQ ID NO:6; the B-chain polypeptide for Dimers 19, 65, and 83 has the amino acid sequence shown in SEQ ID NO:9; and, the B-chain polypeptide for Dimers 20 and 28 has the amino acid sequence shown in SEQ ID NO:10.
2. A composition comprising one or more compounds of claim 1 and a pharmaceutically acceptable carrier.
3. A method for treating diabetes comprising administering to an individual with diabetes a therapeutically effective amount of the composition of claim 2 .
4. The method of claim 3 , wherein the diabetes is Type 1 diabetes, Type 2 diabetes, or gestational diabetes.
5. A method for treating diabetes comprising administering to an individual with diabetes a therapeutically effective amount of the compound of claim 1 .
6. The method of claim 5 , wherein the diabetes is Type 1 diabetes, Type 2 diabetes, or gestational diabetes.
7. A compound having the formula
wherein the disulfide linkages between the Cys 6 and Cys 11 residues of the A-chain polypeptide and the disulfide linkages between the Cys 7 and Cys 20 of the A-chain to the Cys 7 and Cys 19 of the B-chain polypeptide, respectively, are represented by the solid line therebetween; wherein the linking moieties are covalently linked to the epsilon amino acid of the shown lysine residues, wherein the A-chain polypeptide has the amino acid sequence shown in SEQ ID NO:1 and the B-chain polypeptide has the amino acid sequence shown in SEQ ID NO:2.
8. A composition comprising the compound of claim 7 and a pharmaceutically acceptable carrier.
9. A method for treating diabetes comprising administering to an individual with diabetes a therapeutically effective amount of the composition of claim 8 .
10. The method of claim 9 , wherein the diabetes is Type 1 diabetes, Type 2 diabetes, or gestational diabetes.