YM-53601

YM-53601, a squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in vivo^[1]. YM-53601 inhibits squalene synthase derived from human hepatoma cells with an IC₅₀ of 79 nM. Lipid-lowering agent^[2]. YM-53601 is also an inhibitor of farnesyl-diphosphate farnesyltransferase 1 (FDFT1) enzyme activity and abrogates HCV propagation^[3]. In Vitro: YM-53601 inhibits squalene synthase activities in hepatic microsomes from several species of rat, hamster, guinea-pig, rhesus monkey, and human-derived HepG2 cell with IC₅₀s of 90, 170, 46, 45, and 79 nM, respectively^[1].
YM-53601 inhibits conversion of [3H]farnesyl diphosphate to [³H]squalene by hamster liver squalene synthase with the IC₅₀ of 170 nM^[2].
YM-53601 (1 μM) potentiates the susceptibility of H35 cells to thapsigargin, lonidamine, and doxorubicin. YM-53601 (1 μM) reduces the mitochondrial cholesterol levels in both H35 and HepG2 cells^[4]. In Vivo: YM-53601 suppresses cholesterol biosynthesis in rats (ED₅₀, 32 mg/kg)^[1].
YM-53601 also reduces plasma non-HDL cholesterol levels in hamsters by approximately 70% at an oral dose of 50 mg/kg/day for 5 days^[2].
YM-53601 potentiates Doxorubicin-mediated hepatocellular carcinoma cells (HCC) growth arrest and cell death in vivo^[4].