E-5324 is potent cholesterol acyltransferase (ACAT) inhibitor (IC50s: 44 to 190 nM).

ACAT:44 to 190 nM

E-5324 inhibits the incorporation of [3H]oleate into cholesteryl [3H]oleate in a concentration-dependent manner (IC50: 0.44 μM) and it also inhibits [3H]cholesteryl ester synthesis (IC50: 0.41 μM). E-5324 displays no effect on triglyceride synthesis up to 10 μM and it also has no effect on bovine pancreatic cholesterol esterase or lecithin: cholesterol acyltransferase (LCAT) up to 10 μM [1].

Treatment with E-5324 significantly reduces both the wet weight and protein content. A high dose of E-5324 (0.1%) notably decreases the surface involvement by 34% in the aortic arch and by 54% in the thoracic aorta. At the same concentration, it substantially lowers cholesteryl ester and total cholesterol levels in the aortic arch by 60% and 59%, respectively. Furthermore, this dosage markedly reduces ACAT activities in the aortic arch and thoracic aorta by 35% and 44%, respectively. The area under the cholesterol-time curves (AUC) for the duration of the study for control, 0.02% E-5324, and 0.1% E-5324 are 104985±4411, 106096±4476, and 105231±4348 mg×day/dL, respectively [2].