AMG 837 hemicalcium salt

AMG 837 hemicalcium is a potent, orally bioavailable and partial agonist of GPR40/FFA1, inhibits specific [3H]AMG 837 binding at the human FFA1 receptor with a pIC50 of 8.13. AMG 837 hemicalcium could enhance insulin secretion and lower glucose levels in rodents[1][2][3].

Signaling Pathways >> GPCR/G Protein >> GPR40

Research Areas >> Metabolic Disease

pIC50: 8.13 (FFA1)[3]

AMG 837 (1 nM-10 μM) stimulates insulin secretion in a glucose-dependent manner with an EC50 of 142±20 nM on islets isolated from mice[1]. AMG 837 stimulates Ca2+ flux with the EC50s of 13.5, 22.6 and 31.7 nM for human, mouse and rat receptors in CHO cells, respectively[1].

AMG 837 (0.03-0.3 mg/kg; a single p.o.) improves glucose tolerance and enhances insulin secretion in Sprague-Dawley rats[1]. AMG 837 (0.5 mg/kg; p.o.) displays excellent oral bioavailability (%F = 84) and a total plasma Cmax of 1.4 µM[1]. AMG 837 (0.03-0.3 mg/kg; p.o. once daily for 21 days) reduces glucose levels and increases insulin levels following glucose challenge in vivo[1]. Animal Model: 8-week old Sprague-Dawley rats[1] Dosage: 0.03, 0.1, 0.3 mg/kg Administration: A single p.o. administration Result: Reduced the post-prandial glucose with the half-maximal dose of 0.05 mg/kg. Animal Model: 8-week old Zucker Fatty Rats[1] Dosage: 0.03, 0.1, 0.3 mg/kg Administration: Oral gavage once daily for 21 days Result: Decreased glucose AUC values during the glucose tolerance test (GTT) to 7%, 15%, and 25% at 0.03, 0.1 and 0.3 mg/kg, respectively. Increased insulin levels in the mid- and high-dose groups. Not affected body weights during the 21-day treatment.

[1]. Daniel CHL, et, al. AMG 837: a novel GPR40/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodents. PLoS One. 2011; 6(11): e27270.

[2]. Houze JB, et, al. AMG 837: a potent, orally bioavailable GPR40 agonist. Bioorg Med Chem Lett. 2012 Jan 15; 22(2): 1267-70.

[3]. Daniel CHL, et, al. Identification and pharmacological characterization of multiple allosteric binding sites on the free fatty acid 1 receptor. Mol Pharmacol. 2012 Nov;82(5):843-59.