Lanosterol synthase disease prevention and treatment (see Disease Relevance, below). Interest has grown in lanosterol synthase inhibitors as drugs to lower blood cholesterol and treat atherosclerosis. The widely popular statin drugs currently used to lower LDL (low-density lipoprotein) cholesterol function by inhibiting HMG-CoA reductase activity. Because this enzyme catalyzes the formation of precursors far upstream of (S)-2,3-epoxysqualene and cholesterol, statins may negatively influence amounts of intermediates required for other biosynthetic pathways (e.g. synthesis of isoprenoids, coenzyme Q). Thus, lanosterol synthase, which is more closely tied to cholesterol biosynthesis than HMG-CoA reductase, is an attractive drug target. Lanosterol synthase inhibitors are thought to
Discovery and development of statins dominant. CYP3A4 isoenzyme is the most predominant isoform involved in metabolism of lovastatin, simvastatin, atorvastatin and cerivastatin. CYP2C9 isoenzyme is the most predominant isoform involved in metabolism of Fluvastatin, but CYP3A4 and CYP2C8 isoenzymes also contribute to the metabolism of Fluvastatin. Rosuvastatin is metabolized to a small degree by CYP2C9 and to a lesser extent by CYP2C19 isoenzymes. Pravastatin is not metabolized by CYP isoenzymes to any appreciable extent. The statins that have the ability to be metabolized by multiple CYP isoenzymes may therefore avoid drug accumulation when one of the pathways is inhibited by co-administered drugs. With the recent