BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Diacylglycerol O-acyltransferase-2 (DGAT2)

January 21, 2016 8:00 AM UTC

In vitro and mouse studies identified a DGAT2 inhibitor that could help treat dyslipidemia and other metabolic disorders. Screening of a small molecule library in enzymatic assays and optimization of hits yielded a tetrahydroisoquinoline analog that inhibited human DGAT2 with an IC50 of 2 nM. In primary mouse hepatocytes, the analog inhibited triglyceride production with an EC50 of 55 nM. In mice, subcutaneous injection of the inhibitor decreased plasma triglyceride levels compared with vehicle. Next steps could include testing the analog in mouse models of metabolic diseases...