Jane Zhang

TL;DR: Optimize of a series of β-substituted phenylpropanoic acids led to the identification of (S)-3-(4-((4'-(trifluoromethyl)biphenyl-3-yl)methoxy)phenyl)hex-4-ynoic acid (AMG 837) as a potent GPR40 agonist with a superior pharmacokinetic profile and robust glucose-dependent stimulation of insulin secretion in rodents.

TL;DR: GPR40 full agonists AM-1638 and AM-6226 stimulate GLP-1 and GIP secretion from intestinal enteroendocrine cells and increase GSIS from pancreatic islets, leading to enhanced glucose control in the high fat fed, streptozotocin treated and NONcNZO10/LtJ mouse models of type 2 diabetes.

TL;DR: There appear to be three allosterically linked binding sites on FFA1 with agonists specific for each of these sites, and these ligands with their high potencies and strong positive functional cooperativity with endogenous fatty acids have the potential to deliver therapeutic benefits.

TL;DR: Preclinical studies demonstrated that AMG 837 was a potent GPR40 partial agonist which lowered post-prandial glucose levels and support the potential utility of AMG837 for the treatment of type 2 diabetes.

TL;DR: It is shown that allosterism at FFA1 can contribute to postprandial glucose management by stimulating insulin secretion via an extrapancreatic mechanism of action, and that GPR120 in GLP-1 secretion requires further investigation.