BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Sterol O-acyltransferase 2 (SOAT2; ACAT2)

October 15, 2015 7:00 AM UTC

In vitro and mouse studies identified an SOAT2 inhibitor that could help treat atherosclerosis and hypercholesterolemia. Chemical synthesis and in vitro testing of pyripyropene A analogs yielded a compound that inhibited SOAT2 with an IC50 of 11.8 nM and about 6,000-fold greater selectivity for SOAT2 than SOAT1. In apolipoprotein E (APOE)-knockout mice fed a high-cholesterol diet, the compound decreased cholesterol levels in low-density lipoproteins - but not high-density lipoproteins - and decreased the size of aortic atherosclerotic lesions compared with Lipitor atorvastatin or vehicle, without causing observable toxicity in the liver, kidneys or intestines. Next steps could include testing the compound in additional models of hypercholesterolemia and atherosclerosis...