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 bifunctional linkers are covalently linked to the epsilon amino group of the respective B29 lysine residue, wherein the A-chain polypeptide for Dimers 71, 72, 77 and 78 has the amino acid sequence shown in SEQ ID NO:1; and the B-chain polypeptide for Dimers 71, 72, 77 and 78 has the amino acid sequence shown in SEQ ID NO:2, respectively.
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 a composition comprising the insulin receptor partial agonist of claim 2 .
4. The method of claim 3 , wherein the diabetes is Type 1 diabetes, Type 2 diabetes, or gestational diabetes.
5. An insulin dimer comprising:
a first B29 or B28 Lys of a first insulin heterodimer molecule having a first A-chain polypeptide and first B-chain polypeptide and a second B29 or B28 Lys of a second insulin heterodimer having a second A-chain polypeptide and second B-chain polypeptide conjugated together by a bifunctional linker selected from the group consisting of:
6. A compound having the following formula