AMG 837 calcium hydrate (C09-1101-713)

AMG 837 calcium hydrate is a potent, orally bioavailable and partial agonist of GPR40/FFA1 . AMG 837 calcium hydrate inhibits specific [ 3 H]AMG 837 binding at the human FFA1 receptor with a pIC 50 of 8.13. AMG 837 calcium hydrate could enhance insulin secretion and lower glucose levels in rodentsIn VitroAMG 837 (1 nM-10 μM) stimulates insulin secretion in a glucose-dependent manner with an EC 50 of 142±20 nM on islets isolated from mice. AMG 837 stimulates Ca 2+ flux with the EC 50 s of 13.5, 22.6 and 31.7 nM for human, mouse and rat receptors in CHO cells, respectively. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoAMG 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 . AMG 837 (0.03-0.3 mg/kg; a single p.o.) improves glucose tolerance and enhances insulin secretion in Sprague-Dawley rats . AMG 837 (0.5 mg/kg; p.o.) displays excellent oral bioavailability (F = 84%) and a total plasma C max of 1.4 µM . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: 8-week old Zucker Fatty Rats 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. Animal Model: 8-week old Sprague-Dawley rats 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.Form:SolidIC50& Target:pIC50: 8.13 (FFA1). Specification: 0.98 Molecular Formula: C26H21F3O3.1/2Ca.H2O Molecular Weight: 455.45 PubChem CID: 138107175