PF-06427878

PF-06427878 is an orally administered, potent, and selective small molecule inhibitor of diacylglycerol acyltransferase 2 (DGAT2), an enzyme involved in hepatic triglyceride synthesis. Developed by Pfizer, it was investigated as a potential treatment for nonalcoholic steatohepatitis (NASH), obesity, and hyperlipidemia. Preclinical studies demonstrated that PF-06427878 reduced hepatic and plasma triglyceride concentrations and improved liver histology in animal models of NASH. In phase 1 clinical trials in healthy adults, the drug was well tolerated at tested doses and showed reductions in markers of liver function as well as hepatic steatosis. However, development risks related to metabolic liabilities led to its discontinuation after phase 1; subsequent efforts resulted in the discovery of ervogastat (PF-06865571) as a successor compound[1][2][3][4][5][7][10].