Potent and Orally Bioavailable GPR142 Agonists as Novel Insulin Secretagogues for the Treatment of Type 2 Diabetes.
Basic Information
ID: ALA2406902
Journal: ACS Med Chem Lett
Title: Potent and Orally Bioavailable GPR142 Agonists as Novel Insulin Secretagogues for the Treatment of Type 2 Diabetes.
Authors: Toda N, Hao X, Ogawa Y, Oda K, Yu M, Fu Z, Chen Y, Kim Y, Lizarzaburu M, Lively S, Lawlis S, Murakoshi M, Nara F, Watanabe N, Reagan JD, Tian H, Fu A, Motani A, Liu Q, Lin YJ, Zhuang R, Xiong Y, Fan P, Medina J, Li L, Izumi M, Okuyama R, Shibuya S.
Abstract: GPR142 is a G protein-coupled receptor that is predominantly expressed in pancreatic β-cells. GPR142 agonists stimulate insulin secretion in the presence of high glucose concentration, so that they could be novel insulin secretagogues with reduced or no risk of hypoglycemia. We report here the optimization of HTS hit compound 1 toward a proof of concept compound 33, which showed potent glucose lowering effects during an oral glucose tolerance test in mice and monkeys.
CiteXplore: 24900747
DOI: 10.1021/ml400186z
Patent ID: ┄