2. Academic Validation
  3. Discovery of LY3325656: A GPR142 agonist suitable for clinical testing in human

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

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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