1. Academic Validation
  2. AMG 837: a potent, orally bioavailable GPR40 agonist

AMG 837: a potent, orally bioavailable GPR40 agonist

  • Bioorg Med Chem Lett. 2012 Jan 15;22(2):1267-70. doi: 10.1016/j.bmcl.2011.10.118.
Jonathan B Houze 1 Liusheng Zhu Ying Sun Michelle Akerman Wei Qiu Alex J Zhang Rajiv Sharma Michael Schmitt Yingcai Wang Jiwen Liu Jinqian Liu Julio C Medina Jeff D Reagan Jian Luo George Tonn Jane Zhang Jenny Ying-Lin Lu Michael Chen Edwin Lopez Kathy Nguyen Li Yang Liang Tang Hui Tian Steven J Shuttleworth Daniel C-H Lin
Affiliations

Affiliation

  • 1 Amgen Inc. 1120 Veterans Blvd., South San Francisco, CA 94080, USA. jhouze@amgen.com
Abstract

The discovery that certain long chain fatty acids potentiate glucose stimulated Insulin secretion through the previously orphan receptor GPR40 sparked interest in GPR40 agonists as potential antidiabetic agents. Optimization of a series of β-substituted phenylpropanoic acids led to the identification of (S)-3-(4-((4'-(trifluoromethyl)biphenyl-3-yl)methoxy)phenyl)hex-4-ynoic acid (AMG 837) as a potent GPR40 agonist with a superior pharmacokinetic profile and robust glucose-dependent stimulation of Insulin secretion in rodents.

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