AMG 837 is a partial agonist of free fatty acid receptor 1 (FFAR1/GPR40).1 It induces calcium mobilization in CHO cells expressing FFAR1/GPR40 but not FFAR2/GPR43, FFAR3/GPR41, or FFAR4/GPR120 (EC50s = 0.0135, >10, >10, and >10 ?M, respectively).1,2 AMG 837 induces insulin secretion in MIN6 pancreatic β-cells and isolated mouse islets (EC50s = 0.0048 and 0.142 ?M, respectively).1,2 It decreases plasma glucose levels and increases plasma levels of insulin in Zucker fa/fa rats when administered at doses of 0.3, 1, and 3 mg/kg.2 AMG 837 (100 mg/kg) also decreases plasma glucose and increases plasma insulin levels in a mouse model of diabetes induced by a high-fat diet and streptozotocin .3
1.Houze, J.B., Zhu, L., Sun, Y., et al.AMG 837: A potent, orally bioavailable GPR40 agonistBioorg. Med. Chem. Lett22(2)1267-1270(2012) 2.Lin, D.C.-H., Zhang, J., Zhuang, R., et al.AMG 837: A novel GPR40/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodentsPLoS One6(11)e27270(2011) 3.Luo, J., Swaminath, G., Brown, S.P., et al.A potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodentsPLoS One7(10)e46300(2012)