AMG 837

Description: AMG 837 is a partial GPR40 agonist with an EC50 value of 13 nM, showcasing 85% of the maximal activity displayed by DHA in standard assay conditions, indicating its high potency and selectivity in vitro. This compound excels as a GPR40 agonist with a notable pharmacokinetic profile, effectively stimulating insulin secretion in a glucose-dependent manner in rodents and demonstrating potent insulin secretion stimulation in MIN6 cells, with efficacy comparable to that observed in aequorin Ca2+-flux assays. Moreover, AMG 837 exhibits a two-fold increase in potency compared to its racemic counterpart on GPR40, with demonstrated activity across rat and mouse GPR40 versions (EC50 = 23 and 13 nM, respectively). It lacks significant activity against PPARalpha, delta, and gamma in cell-based assays, and an analysis against an external panel of 64 receptors revealed negligible activity, except for a weak inhibition (IC50 = 3 µM) on the a2-adrenergic receptor. Target: Others. Smiles: CC#C[C@@H](CC(O)=O)c1ccc(OCc2cccc(c2)-c2ccc(cc2)C(F)(F)F)cc1. References: Houze JB, et al. AMG 837: a potent, orally bioavailable GPR40 agonist. Bioorg Med Chem Lett. 2012 Jan 15,22(2):1267-70.