Biological Activity
pf-04620110 is a potent, selective and orally-bioavailable inhibitor of diacylglycerol acyltransferase 1 (dgat-1), an enzyme catalyzing the final committed step in the biosynthesis of triglycerides, that inhibits dgat-1 with values of 50% inhibition concentration ic50 of 19 nm and 8 nm in human and ht-29 cells respectively. pf-04620110 displays a highly selective, more than 100 fold, inhibition against dgat-1 rather than a range of lipid processing enzymes, including human dgat-2, human acyl-coa:cholesterol acyltransferase 1, human acyl-coa:wax alcohol acyltransferase 1, human acyl-coa:wax alcohol acyltransferase 2, human acyl-coa:monacylglycerol acyltransferase 2, human acyl-coa:monacylglycerol acyltransferase 3 and mouse mgat 1.lee kr, choi sh, song js, seo h, chae yj, cho he, ahn jh, ahn sh, bae ma. determination of pf-04620110, a novel inhibitor of diacylglycerol acyltransferase-1, in rat plasma using liquid chromatography-tandem mass spectrometry and its application in pharmacokinetic studies. biomed chromatogr. 2013; 27(7):846-852.robert l. dow *, jian-cheng li , michael p. pence , e. michael gibbs , jennifer l. laperle , john litchfield , david w. piotrowski , michael j. munchhof , tara b. manion , william j. zavadoski , gregory s. walker , r. kirk mcpherson , susan tapley , eliot sugarman , angel guzman-perez , and paul dasilva-jardine discovery of pf-04620110, a potent, selective, and orally bioavailable inhibitor of dgat-1. acs med. chem. lett., 2011, 2 (5), pp 407–412
Biochem/physiol Actions
PF-04620110 is known to regulate gut hormones. Inhibition of DGAT1 might serve as a good approach for the treatment of obesity and type 2 diabetes. DGAT1 inhibition might increase the oxidation of fatty acids, thus it is found to be protective against hepatic steatosis.
