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

  • Bioorg Med Chem Lett. 2020 Mar 1;30(5):126857. doi: 10.1016/j.bmcl.2019.126857.
Lian Zhu Liu  1 ,  Tianwei Ma  2 ,  Jingye Zhou  2 ,  Zhi Long Hu  2 ,  Xue Jun Zhang  2 ,  Hai Zhen Zhang  2 ,  Mi Zeng  2 ,  Jia Liu  2 ,  Lei Li  2 ,  Yi Jiang  2 ,  Zack Zou  2 ,  Fan Wang  2 ,  Lei Zhang  2 ,  Jianfeng Xu  2 ,  Jingru Wang  2 ,  Fei Xiao  2 ,  Xiankang Fang  2 ,  Haixia Zou  1 ,  Alexander M Efanov  3 ,  Melissa K Thomas  3 ,  Hua V Lin  2 ,  Jiehao Chen  4
Affiliations
  • 1. Lilly China Research and Development Center (LCRDC), Eli Lilly & Company, Building 8, 338 Jia Li Lue Road, Shanghai 201203, PR China; Lilly China Innovation and Partnerships (LCIP), Eli Lilly & Company, 16F, Tower1 HKRI, Taikoo Hui 288 Shimenyi Road, Shanghai 200041, PR China.
  • 2. Lilly China Research and Development Center (LCRDC), Eli Lilly & Company, Building 8, 338 Jia Li Lue Road, Shanghai 201203, PR China.
  • 3. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States.
  • 4. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States. Electronic address: [email protected].
PMID: 31982234 DOI: 10.1016/j.bmcl.2019.126857
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.

Keywords
GPR142 agonist; Glucose-dependent insulin secretion; Metabolism; Type 2 diabetes.
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