Pactimibe sulfate (CS-505) is a dual ACAT1/2 inhibitor with IC50s of 4.9 µM and 3.0 µM, respectively. Pactimibe sulfate (CS-505) inhibits ACAT with IC50s of 2.0 µM, 2.7 µM, 4.7 µM in the liver, macrophages and THP-1 cells, respectively[1]. Pactimibe sulfate (CS-505) noncompetitively inhibits oleoyl-CoA with a Ki value of 5.6 µM. Moreover, Pactimibe sulfate (CS-505) obviously inhibits cholesteryl ester formation with an IC50 of 6.7 µM. Pactimibe sulfate (CS-505) possesses anti-atherosclerotic potential with lowering plasma cholesterol activity[2].
Pactimibe sulfate (CS-505) induces moderate ACAT inhibition in monocyte-derived macrophages, leading to the suppression of foam cell formation[2].
Pactimibe sulfate (CS-505; 60 and 200 mg/kg/day; oral gavage; twice a day; 12 weeks) induces an inhibition for ACAT-1 and ACAT-2, causing a reduction of plasma cholesterol but no influence on macrophage- or collagen-positive areas[3].
References:
[1]. Naoki Terasaka, et al. ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice. Atherosclerosis. 2007 Feb;190(2):239-47.
[2]. Ken Kitayama, et al. Importance of acyl-coenzyme A:cholesterol acyltransferase 1/2 dual inhibition for anti-atherosclerotic potency of pactimibe. Eur J Pharmacol. 2006 Jul 1;540(1-3):121-30.
[3]. Yasunobu Yoshinaka, et al. A selective ACAT-1 inhibitor, K-604, stimulates collagen production in cultured smooth muscle cells and alters plaque phenotype in apolipoprotein E-knockout mice. Atherosclerosis. 2010 Nov;213(1):85-91.