Discovery of a novel potent GPR40 full agonist

Authors :: Eric Arnoult
Meghan Hall
Monicah A. Otieno
Hui Huang
Tonya Martin
Jose Silva
Joe Gunnet
Jianying Liu
Yuanping Wang
Shuyuan Zhao
Sanath K. Meegalla
June Xu
Alessandro Pocai
Mark R. Player
Brian Rady
S. Paul Lee
Source :: Bioorganic & Medicinal Chemistry Letters. 28:720-726
Publication Year :: 2018
Publisher :: Elsevier BV, 2018.
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.

Tools