AM-4668

AM-4668 is a potent and selective small molecule agonist of the G protein-coupled receptor 40 (GPR40), also known as free fatty acid receptor 1 (FFA1). It was developed for the treatment of type 2 diabetes, aiming to enhance insulin secretion in response to elevated glucose levels. Preclinical studies show that AM-4668 has high potency with EC50 values of 3.6 nM and 36 nM in different cell-based assays targeting GPR40[1][4][6]. The compound demonstrates excellent pharmacokinetic properties across species and is more potent than AMG 837, another GPR40 agonist[3]. While primarily characterized as a selective GPR40 agonist, research has also explored dual FFA1/PPARδ agonists for improved anti-diabetic effects; however, AM-4668 itself is not reported as a dual agonist but rather served as a template for such hybrid molecules[7]. The drug was initially developed by Amgen.