Therapeutics: Activator protein-1 (AP-1; JUN); CDK5 regulatory subunit associated protein 1 (CDK5RAP1)

Cell culture and mouse studies suggest AP-1 inhibitors could help treat Type II diabetes involving CDK5RAP1 mutations. In human pancreatic β cells generated from induced pluripotent stem (iPS) cells harboring mutant CDK5RAP1, an AP-1 inhibitor tool compound decreased insulin-induced cell death and increased glucose-stimulated insulin secretion compared with vehicle. In mice transplanted with the iPS cell-derived β cells, the AP-1 inhibitor increased glucose-stimulated insulin secretion and glucose tolerance. Next steps include identifying and testing therapies to treat Type II diabetes involving other mutant genes.

Toyama Chemical Co. Ltd. and Roche have R7277, an AP-1 inhibitor, in Phase II testing to treat rheumatoid arthritis (RA). ...