AMG 837 calcium hydrate

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AMG 837 水合钙是一种有效的 GPR40 激动剂，EC50 为 13 nM。 AMG 837 水合钙还表现出比 GPR41、GPR43 和 GPR120 更高的选择性 (EC50 > 10,000 nM)。

AMG 837 calcium hydrate is a potent GPR40 agonist with an EC50 of 13 nM. AMG 837 calcium hydrate also shows highly selective over GPR41, GPR43, and GPR120 (EC50 > 10,000 nM).(In Vitro):GPR40 agonist AMG 837 displayed the expected two-fold increase in potency on GPR4 (EC50: 13 nM) compared to the racemic compound and its activity crossed over to the rat and mouse forms of GPR40 (EC50s: 23/13 nM). AMG 837 was a partial agonist on GPR40 with maximal activity 85% of that shown by DHA. An external panel of 64 receptors also revealed no significant activity with the exception of weak inhibition (IC50: 3 μM) on the α2-adrenergic receptor .(In Vivo):In rats, AMG 837 increases insulin release when glucose levels are elevated . AMG 837 was dosed at 0.03, 0.1 and 0.3 mg/kg by oral gavage daily for 21-days. Thirty minutes following the first dose, an IPGTT was performed. AMG 837 improved glucose levels during the IPGTT (figure 5A) with a decrease in glucose AUC of 17%, 34% (p<0.001), and 39% (p<0.001) at 0.03, 0.1 and 0.3 mg/kg, respectively. This was associated with increased insulin secretion following glucose administration.

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.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.

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.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 Cmax of 1.4 μM. 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.

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Cell Cycle/DNA Damage

GPR

GPR

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1259389-38-2

932.969

C52H42CaF6O7

>98% (HPLC)

In Vitro:?DMSO : ≥ 42 mg/mL (92.22 mM)

O.[Ca++].CC#CC(CC([O-])=O)c1ccc(OCc2cccc(c2)-c2ccc(cc2)C(F)(F)F)cc1.CC#CC(CC([O-])=O)c1ccc(OCc2cccc(c2)-c2ccc(cc2)C(F)(F)F)cc1

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(-20℃)

With Ice Pack

≥ 2 years