1 research outputs found
Intestinally Targeted Diacylglycerol Acyltransferase 1 (DGAT1) Inhibitors Robustly Suppress Postprandial Triglycerides
High DGAT1 expression levels in the small intestine highlight
the
critical role this enzyme plays in nutrient absorption. Identification
of inhibitors which predominantly inhibit DGAT1 in the gut is an attractive
drug discovery strategy with anticipated benefits of reduced systemic
toxicity. In this report we describe our discovery and optimization
of DGAT1 inhibitors whose plasma exposure is minimized by the action
of transporters, including the P-glycoprotein transporter. The impact
of this unique absorption profile on efficacy in rat and dog efficacy
models is presented