Discovery of a novel potent GPR40 full agonist

  • Bioorg Med Chem Lett. 2018 Feb 15;28(4):720-726. doi: 10.1016/j.bmcl.2018.01.013.
Sanath K Meegalla  1 ,  Hui Huang  1 ,  Tonya Martin  1 ,  June Xu  1 ,  Shuyuan Zhao  1 ,  Jianying Liu  1 ,  Meghan Hall  1 ,  Joe Gunnet  1 ,  Yuanping Wang  1 ,  Brian Rady  1 ,  Jose Silva  2 ,  Monicah Otieno  2 ,  Eric Arnoult  3 ,  S Paul Lee  1 ,  Alessandro Pocai  1 ,  Mark R Player  4
Affiliations
  • 1. CVM Discovery, Janssen Research & Developmen, LLC, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
  • 2. PDS-TPL-TOX, Janssen Research & Development, LLC, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
  • 3. Computational Chemistry, Janssen Research & Development, LLC, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
  • 4. CVM Discovery, Janssen Research & Developmen, LLC, Welsh and McKean Roads, Spring House, PA 19477-0776, USA. Electronic address: [email protected].
PMID: 29366647 DOI: 10.1016/j.bmcl.2018.01.013
Abstract

Compound 12 is a GPR40 agonist that realizes the full magnitude of efficacy possible via GPR40 receptor agonism. In vitro and in vivo studies demonstrated superior glucose lowering by 12 compared to fasiglifam (TAK-875), in a glucose dependent manner. The enhanced efficacy observed with the full agonist 12 was associated with both direct and indirect stimulation of Insulin secretion.

Keywords
GPCR; GPR40 full agonist; GSIS; Insulin secretagogues; Type 2 diabetes mellitus.
Products