AMG 837

AMG 837 was found to be a partial agonist on GPR40 with maximal activity 85% of that shown by DHA under our standard assay conditions. Overall, AMG 837 was both highly potent and selective in vitro. AMG 837 is a potent GPR40 agonist(EC50=13 nM) with a superior pharmacokinetic profile and robust glucose-dependent stimulation of insulin secretion in rodents and is a highly potent stimulator of insulin secretion in MIN6 cells with an EC50 comparable to that seen in the aequorin Ca2+-flux assay. IC50 value: 13 nM (EC50) [1] Target: GPR40 agonist AMG 837 displayed the expected two-fold increase in potency on GPR4 (EC50 = 13 [±7] nM) compared to the racemic compound and its activity crossed over to the rat and mouse forms of GPR40 (EC50 = 23 and 13 nM, respectively). showed no significant activity in cell-based assays against PPARα, δ, and γ. An external panel of 64 receptors also revealed no significant activity with the exception of weak inhibition (IC50 = 3 uM) on the a2-adrenergic receptor.

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