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Potent and Orally Bioavailable GPR142 Agonists as Novel Insulin Secretagogues for the Treatment of Type 2 Diabetes.

ABSTRACT: GPR142 is a G protein-coupled receptor that is predominantly expressed in pancreatic ?-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.

SUBMITTER: Toda N

PROVIDER: S-EPMC4027368 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Potent and Orally Bioavailable GPR142 Agonists as Novel Insulin Secretagogues for the Treatment of Type 2 Diabetes.

Toda Narihiro N Hao Xiaolin X Ogawa Yasuyuki Y Oda Kozo K Yu Ming M Fu Zice Z Chen Yi Y Kim Yongjae Y Lizarzaburu Mike M Lively Sarah S Lawlis Shauna S Murakoshi Michiko M Nara Futoshi F Watanabe Nobuaki N Reagan Jeff D JD Tian Hui H Fu Angela A Motani Alykhan A Liu Qingxiang Q Lin Yi-Jyun YJ Zhuang Run R Xiong Yumei Y Fan Peter P Medina Julio J Li Leping L Izumi Masanori M Okuyama Ryo R Shibuya Satoshi S

ACS medicinal chemistry letters 20130617 8

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. ...[more]

PMID: 24900747

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