AM-6226

AM-6226 is a potent, orally bioavailable small molecule that acts as a full agonist of the G-protein-coupled receptor 40 (GPR40, also known as free fatty acid receptor 1 or FFA1). GPR40 is primarily expressed in pancreatic islets and enteroendocrine L-cells. Activation of this receptor by AM-6226 stimulates the secretion of incretin hormones such as GLP-1 and GIP from intestinal enteroendocrine cells and enhances glucose-stimulated insulin secretion (GSIS) from pancreatic islets. This dual action leads to improved glycemic control, demonstrated by significant glucose lowering in preclinical models including high-fat-fed, streptozotocin-treated mice and cynomolgus monkeys. The drug was developed to explore the therapeutic potential for type 2 diabetes by leveraging the powerful mechanism of GPR40 full agonism[1][3][7][10].