PF-06424439 is an orally bioavailable inhibitor of diacylglycerol acyltransferase 2 (DGAT-2; IC50 = 14 nM). It is selective for DGAT-2 over the related acyltransferases DGAT-1, MGAT-2, and MGAT-3 (IC50s = >50 μM). PF-06424439 (0.1-10 mg/kg) reduces plasma triglyceride levels in sucrose-fed rats in a dose-dependent manner. It also reduces plasma levels of cholesterol and triglycerides as well as hepatic triglycerides in LDL receptor knockout mice fed a high-fat, high-cholesterol diet when administered at a dose of 60 mg/kg per day.
