Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT-1) is a sterol O-acyltransferase that catalyzes the formation of fatty acid-cholesterol esters, an important step in lipoprotein assembly and dietary cholesterol absorption. CI-976 is a potent, selective inhibitor of ACAT-1 (IC50 = 73 nM). It is orally bioavailable and decreases plasma total cholesterol, very low density lipoprotein (VLDL) cholesterol, LDL cholesterol, apolipoprotein B, liver cholesteryl esters, and VLDL and LDL cholesteryl ester content in rabbits given a diet that induces hypercholesterolemia. CI-976 also diminishes atherosclerotic activity in hypercholesterolemic rabbits.
