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RP-64477
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RP-64477
CAS No. : 135239-65-5
MCE 站:RP-64477
产品活性:RP-64477 是胆固醇酯化酶酰基辅酶 A:胆固醇 O-酰基转移酶 (ACAT) 的有效抑制剂。
研究领域:Metabolic Enzyme/Protease
作用靶点:Acyltransferase
In Vitro: RP-64477 is a potent inhibitor of the cholesterol esterifying enzyme Acyl-coenzyme A:cholesterol O-acyltransferase (ACAT). Inhibitory potencies of RP-64477 in vitro in tissue preparations are obtained from a range of species and in human cell cultures. For animal tissues, IC50 values in the range 6 to 283 nM are recorded, with no obvious species/tissue differences apparent. Potent inhibitory activity of RP-64477 is also recorded in human cell lines of hepatic (HepGZ), intestinal (CaCo-2), and monocytic (THP-1) origin with IC50s of 503, 113, and 180 nM, respectively. No inhibitory activity is recorded against rat PCEH or LCAT at test concentrations up to 200 μM and 20 μM, respectively.
In Vivo: Administration of RP-64477 (0.01% and 0.03% w/w by diet) reduces significantly plasma cholesterol levels in cholesterol/cholic acid-fed rats by 29% and 61%, respectively. Food consumption is not affected by dietary incorporation of RP-64477. Animals receiving RP-64477 (10 and 30 mg/kg b.i.d.) over this period exhibit significantly lower plasma cholesterol levels on both days 4 and 7 when compare to values recorded from vehicle treated animals fed the cholesterol-containing diet. Compare to cholesterol-fed controls, after 7 days of dosing, plasma cholesterol levels are 35% and 53% lower in animals receiving 10 and 30 mg/kg b.i.d. doses of RP-64477, respectively.
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