2. Academic Validation
  3. Discovery of a novel potent GPR40 full agonist

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

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: mplayer@its.jnj.com.
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.

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