Benzoic acid, 3-[[[[2-[(3R)-3-(2-ethoxyphenoxy)-1-piperidinyl]-5-pyrimidinyl]carbonyl]amino]methyl]-

Biological Activity

PF-06427878 is an orally active, potent and selective diacylglycerol acyltransferase 2 inhibitor (human/r at DGAT2 IC50 = 99/202 nM; >470-fold selectivity over DGAT1, MGAT1/2/3) th at inhibits DGAT2-dependent triglyceride (TG) synthesis in primary human hepatocytes (IC50 = 11.6 nM in the presence of DGAT1 inhibitor PF-04620110). PF-06427878 reduces hepatic and circulating plasma TG levels as well as lipogenic gene expression in rats maintained on a Western-type diet (0.3-30 mg/kg bid. po.). Likewise, PF-06427878 significantly improves steatosis and hepatocellular ballooning with a decrease in lobular inflammation in a murine nonalcoholic steatohepatitis (NASH) model (2 or 20 mg/kg bid. po.).