Acyl-Coenzyme A:cholesterol acyltransferases (ACAT1 and ACAT2) catalyze the formation of cholesterol esters from cholesterol and long chain fatty acyl-coenzyme A, and may play a role in the development of atherosclerosis. Avasimibe is an orally bioavailable inhibitor of ACAT (IC50s = 24 and 9.2 μM for ACAT1 and ACAT2, respectively). It reduces foam cell formation in human macrophages in vitro, enhancing free cholesterol efflux and inhibiting the uptake of modified LDL and dose-dependently reduces plasma total triglyceride and VLDL cholesterol levels in cholesterol-fed animal models. Avasimibe inhibition of ACAT has been used to decrease amyloid β generation in models of Alzheimer’s disease.
