Discovery of TUG-770: A Highly Potent Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist for Treatment of Type 2 Diabetes

  • ACS Med Chem Lett. 2013 May 9;4(5):441-445. doi: 10.1021/ml4000673.
Elisabeth Christiansen  1 ,  Steffen V F Hansen ,  Christian Urban ,  Brian D Hudson ,  Edward T Wargent ,  Manuel Grundmann ,  Laura Jenkins ,  Mohamed Zaibi ,  Claire J Stocker ,  Susanne Ullrich ,  Evi Kostenis ,  Matthias U Kassack ,  Graeme Milligan ,  Michael A Cawthorne ,  Trond Ulven
Affiliations
  • 1. Department of Physics, Chemistry and Pharmacy, University of Southern Denmark , Campusvej 55, DK-5230 Odense M, Denmark.
PMID: 23687558 DOI: 10.1021/ml4000673
Abstract

Free Fatty Acid Receptor 1 (FFA1 or GPR40) enhances glucose-stimulated Insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of Type 2 Diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing.

Keywords
FFA1 agonist; GPR40 agonist; TUG-770; Type 2 diabetes; free fatty acid receptor; insulin secretagogue.
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