PF-06427878 is a potent, selective, oral DGAT2 inhibitor with IC50 of 99/202 nM for human/rat DGAT2, >470-fold selectivity over DGAT1 and MGAT1/2/3.
PF-06427878 inhibits DGAT2-dependent triglyceride (TG) synthesis in primary human hepatocytes with IC50 of 11.6 nM.
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.).
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.).
