Description
Pactimibe (CS-505 free base) is a dual ACAT1/2 inhibitor with IC 50 s of 4.9 µM and 3.0 µM, respectively. Pactimibe (CS-505 free base) inhibits ACAT with IC 50 s of 2.0 µM, 2.7 µM, 4.7 µM in the liver, macrophages and THP-1 cells, respectively Pactimibe (CS-505 free base) noncompetitively inhibits oleoyl-CoA with a K i value of 5.6 µM. Moreover, Pactimibe (CS-505 free base) obviously inhibits cholesteryl ester formation with an IC 50 of 6.7 µM. Pactimibe (CS-505 free base) possesses anti-atherosclerotic potential with lowering plasma cholesterol activity. In VitroPactimibe (CS-505 free base) induces moderate ACAT inhibition in monocyte-derived macrophages, leading to the suppression of foam cell formation. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoPactimibe (CS-505 free base; 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male C57BL/6J ApoE −/− mice aged 8-week-oldDosage: 60 and 200 mg/kg/day Administration: Oral gavage; twice a day; 12 weeks Result: Decreased plasma cholesterol levels by 39% and 74% at the administration of 60 and 200 mg/kg/dayForm:SolidIC50& Target:ACAT1:4.9 µM (IC:50:):ACAT2:3.0 µM (IC:50:):ACAT:2 µM (IC:50:, in the liver):ACAT:2.7 µM (IC:50:, in macrophages):ACAT:4.7 µM (IC:50:, in THP-1 cells):oleoyl-CoA:5.6 µM (Ki):cholesteryl ester formation:6.7 µM (IC:50:)