E-5324

E-5324 is potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT) with IC₅₀s of 44 to 190 nM. IC50 & Target: IC50: 44 to 190 nM (ACAT)^[1] In Vitro: E-5324 is a potent ACAT inhibitor with IC₅₀s of 44 to 190 nM in microsomes. E-5324 shows no effect on triglyceride synthesis up to 10 μM. E-5324 also has no effect on bovine pancreatic cholesterol esterase or lecithin: cholesterol acyltransferase (LCAT) up to 10 μM. E-5324 inhibits the incorporation of [³H]oleate into cholesteryl [³H]oleate in a concentration-dependent manner with an IC₅₀ of 0.44 μM. E-5324 also inhibits [³H]cholesteryl ester synthesis with an IC₅₀ of 0.41 μM^[1]. In Vivo: The areas under the cholesterol-time curves for duration of this study (AUC) for control, E-5324 0.02% and E-5324 0.1% are 104985±4411, 106096±4476 and 105231±4 348 mg×day/dL, respectively. The high dose of E-5324 (0.1%) significantly reduces the surface involvement by 34% and 54% in the aortic arch and thoracic aorta, respectively. E-5324 treatment significantly reduces the wet weight and protein content. In the aortic arch, the high dose of E-5324 (0.1%) significantly reduces both cholesteryl ester and total cholesterol by 60% and 59%, respectively. The high dose of E-5324 (0.1%) markedly reduces the ACAT activities in the aortic arch and thoracic aorta by 35% and 44%, respectively^[2].