MK-2305

MK-2305 is a potent and selective **partial agonist** of the **G protein-coupled receptor 40** (GPR40, also known as FFAR1), developed for its potential antidiabetic effects. It selectively activates GPR40, with an EC50 of 6 nM (rat GPR40), leading to increased **glucose-stimulated insulin secretion** (GSIS) from pancreatic beta cells. MK-2305 does not directly act on the liver, as GPR40 is not expressed there, but it decreases endogenous glucose production, primarily by reducing gluconeogenesis in rodents. Significant lowering of both fasting and fed blood glucose has been demonstrated in diabetic animal models, as well as improved glucose tolerance and reduced hemoglobin A1c after chronic administration. The compound displays over 2,000-fold selectivity for GPR40 over related receptors and PPARs. While MK-2305 showed promising pharmacology in preclinical studies, there is no evidence of active clinical development or human data published.