Validation of diacyl glycerolacyltransferase I as a novel target for the treatment of obesity and dyslipidemia using a potent and selective small molecule inhibitor
G Zhao, AJ Souers, M Voorbach, HD Falls… - Journal of medicinal …, 2008 - ACS Publications
G Zhao, AJ Souers, M Voorbach, HD Falls, B Droz, S Brodjian, YY Lau, RR Iyengar, J Gao…
Journal of medicinal chemistry, 2008•ACS PublicationsA 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.
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.
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.
ACS Publications