RP-64477 is identified as a powerful inhibitor of Acyl-coenzyme A:cholesterol O-acyltransferase (ACAT), an enzyme essential for cholesterol esterification. It demonstrates inhibitory effects across a variety of species and tissues, with IC50 values ranging from 6 to 283 nM, indicating a broad spectrum of activity without noticeable differences between species or tissues. Additionally, RP-64477 shows significant inhibition in human cell lines derived from hepatic (HepGZ), intestinal (CaCo-2), and monocytic (THP-1) origins, with IC50s of 503, 113, and 180 nM, respectively. It does not inhibit rat PCEH or LCAT up to concentrations of 200 μM and 20 μM, respectively[1].
体内研究
Dietary incorporation of RP-64477 at 0.01% and 0.03% w/w significantly lowers plasma cholesterol levels in cholesterol/cholic acid-fed rats by 29% and 61%, respectively, without affecting food intake. This reduction in plasma cholesterol levels is also observed with RP-64477 doses of 10 and 30 mg/kg b.i.d., showing a 35% and 53% decrease, respectively, after 7 days compared to cholesterol-fed controls[1].
体外研究
RP-64477 is identified as a powerful inhibitor of Acyl-coenzyme A:cholesterol O-acyltransferase (ACAT), an enzyme essential for cholesterol esterification. It demonstrates inhibitory effects across a variety of species and tissues, with IC50 values ranging from 6 to 283 nM, indicating a broad spectrum of activity without noticeable differences between species or tissues. Additionally, RP-64477 shows significant inhibition in human cell lines derived from hepatic (HepGZ), intestinal (CaCo-2), and monocytic (THP-1) origins, with IC50s of 503, 113, and 180 nM, respectively. It does not inhibit rat PCEH or LCAT up to concentrations of 200 μM and 20 μM, respectively[1].
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