Effect of sterol biosynthesis inhibitor, SSF-109, on cholesterol synthesis in isolated rat hepatocytes.

The inhibitory effect of SSF-109 on cholesterol synthesis in isolated hepatocytes was studied using a radio-high-performance liquid chromatography system, and the results were compared with those of other inhibitors, triparanol and AMO-1618. SSF-109 caused accumulation of two trimethylsterols: lanosterol and 24-dihydrolanosterol. The distribution profile of [2-14C]mevalonate-originated radioactivity in cholesterol, lanosterol, dihydrolanosterol, 2,3-oxidosqualene, and squalene indicates that SSF-109 inhibits the 14 alpha-methyl demethylase activity. Triparanol accumulated the radioactivity of [2-14C]mevalonate in desmosterol and 2,3-oxidosqualene suggesting that triparanol inhibits sterol delta 24-reductase and 2,3-oxidosqualene cyclase. AMO-1618 caused enrichment of the radioisotope from [2-14C]mevalonate in 2,3-oxidosqualene but reduced it in squalene, suggesting that AMO-1618 acts on 2,3-oxidosqualene cyclase and some enzyme that catalizes a metabolic pathway between mevalonate and squalene.