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

Journal of Medicinal Chemistry
Gang ZhaoPhilip R Kym

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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Citations

Nov 26, 2008·The Journal of Biological Chemistry·Michelle Y S ShihRobert V Farese
May 25, 2013·Annual Review of Nutrition·Kelly V RugglesStephen L Sturley
Jan 1, 2009·American Journal of Physiology. Endocrinology and Metabolism·Yuguang Shi, Dong Cheng
Feb 4, 2010·The Journal of Clinical Investigation·Suneil K KoliwadRobert V Farese
Nov 2, 2012·The Journal of Clinical Investigation·Joel T HaasRobert V Farese
Sep 2, 2010·Journal of Lipid Research·Jenson QiMargery A Connelly
Sep 2, 2008·Journal of Lipid Research·Chi-Liang Eric YenRobert V Farese
Jan 21, 2014·Biochimica Et Biophysica Acta·Sarah A ScottH Alex Brown
Jun 18, 2014·Lipids·Michael S GreerRandall J Weselake
Jun 19, 2012·Progress in Lipid Research·Qin LiuRandall J Weselake
Apr 26, 2011·Pharmacology & Therapeutics·John C Clapham, Jonathan R S Arch
Jun 2, 2009·Current Opinion in Chemical Biology·Thomas E Hughes
Dec 2, 2008·Biochimica Et Biophysica Acta·Tobias C Walther, Robert V Farese
May 30, 2008·Pharmacology & Therapeutics·Victor A ZammitAndrew Proven
Mar 13, 2014·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·A ChatzigeorgiouM Koutsilieris
Dec 22, 2009·Expert Opinion on Therapeutic Patents·Andrew J KingAndrew J Souers
Sep 10, 2014·Medicina clínica·Manuel Puig-Domingo, Silvia Pellitero
Feb 26, 2014·The International Journal of Neuropsychopharmacology·R Madelaine ParedesConsuelo Walss-Bass
Jul 19, 2016·ACS Chemical Biology·Nasi LiG Ekin Atilla-Gokcumen
Sep 19, 2014·Journal of Lipid Research·Chi-Liang Eric YenMei-I Yen
Mar 5, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chun-Ching ShihHui-Ya Ho
Dec 1, 2017·World Journal of Gastrointestinal Pathophysiology·Benjamin S MaciejewskiClaire M Steppan
Jan 26, 2017·Circulation Research·Andrew KuoWilliam C Sessa

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