2. Academic Validation
  3. Validation of diacyl glycerolacyltransferase I as a novel target for the treatment of obesity and dyslipidemia using a potent and selective small molecule inhibitor

Validation of diacyl glycerolacyltransferase I as a novel target for the treatment of obesity and dyslipidemia using a potent and selective small molecule inhibitor

  • J Med Chem. 2008 Feb 14;51(3):380-3. doi: 10.1021/jm7013887.
Gang Zhao 1,  Andrew J Souers,  Martin Voorbach,  H Doug Falls,  Brian Droz,  Sevan Brodjian,  Yau Yi Lau,  Rajesh R Iyengar,  Ju Gao,  Andrew S Judd,  Seble H Wagaw,  Matthew M Ravn,  Kenneth M Engstrom,  John K Lynch,  Mathew M Mulhern,  Jennifer Freeman,  Brian D Dayton,  Xiaojun Wang,  Nelson Grihalde,  Dennis Fry,  David W A Beno,  Kennan C Marsh,  Zhi Su,  Gilbert J Diaz,  Christine A Collins,  Hing Sham,  Regina M Reilly,  Michael E Brune,  Philip R Kym
Affiliations

Affiliation

  • 1 Metabolic Disease Research, Abbott Laboratories, Abbott Park, IL 60064, USA.
PMID: 18183944 DOI: 10.1021/jm7013887
Abstract

A highly potent and selective DGAT-1 inhibitor was identified and used in rodent models of obesity and postprandial chylomicron excursion to validate DGAT-1 inhibition as a novel approach for the treatment of metabolic diseases. Specifically, compound 4a conferred weight loss and a reduction in liver triglycerides when dosed chronically in DIO mice and depleted serum triglycerides following a lipid challenge in a dose-dependent manner, thus, reproducing major phenotypical characteristics of DGAT-1(-/-) mice.

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