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Discovery of LY3325656: A GPR142 agonist suitable for clinical testing in human

Lian Zhu Liu,Tianwei Ma,Jingye Zhou, Zhi Long Hu, Xue Jun Zhang, Hai Zhen Zhang, Mi Zeng,Jia Liu, Lei Li, Yi Jiang, Zack Zou,Fan Wang, Lei Zhang,Jianfeng Xu,Jingru Wang,Fei Xiao,Xiankang Fang,Haixia Zou,Alexander M. Efanov,Melissa K. Thomas,Hua Lin, Jiehao Chen

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS（2020）

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Abstract
The discovery and optimization of a novel series of GPR142 agonists are described. These led to the identification of compound 21 (LY3325656), which demonstrated anti-diabetic benefits in pre-clinical studies and ADME/PK properties suitable for human dosing. Compound 21 is the first GPR142 agonist molecule advancing to phase 1 clinic trials for the treatment of Type 2 diabetes.
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Key words
Type 2 diabetes,Glucose-dependent insulin secretion,GPR142 agonist,Metabolism
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