Description
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.
Uses
CI 976 has been used as an acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor:
- to analyze its anti-hepatitis C virus (HCV) activity in Huh7.5.1 cells
- to treat Neuro-2a cells to test its effect on plasma membrane integrated density of α4-SEPβ2 or α6-SEPβ2β3 nicotinic acetylcholine receptors (nAChRs)
- to study its effects on the anti-angiogenic activity of pyripyropenes in human umbilical vein endothelial cells
Uses
CI-976 is a selective inhibitor of Acyl-coenzyme A: cholesterol Acyltransferase 1 (ACAT-1), a sterol O-acetyltransferase that catalyzes information of fatty acid-cholesterol esters. Orally bioavailable and decreses plasma total cholesterol
Definition
ChEBI: 2,2-dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide is an anilide.
Biological Activity
Selective acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitor (IC 50 = 0.073 μ M). Lowers non-high density lipoprotein (HDL)-cholesterol and increases HDL-cholesterol concentrations in rats with pre-established dyslipidaemia. Orally active.
Biochem/physiol Actions
CI-976, a new trimethoxy fatty acid anilide, is a potent and specific inhibitor of liver and intestinal acyl coenzyme A; cholesterol acyltransferase (ACAT) in vitro. CI-976 decreased non-high density lipoprotein (HDL)-cholesterol and increased HDL-cholesterol in rats with pre-established dyslipidemia. High performance gel chromatographic separation of plasma lipoproteins also revealed that CI-976, but not CL 277,082, lowered low density lipoprotein (LDL)-cholesterol and elevated HDL-cholesterol.
