sterol biosynthesis inhibitor

AY 9944 is a specific cholesterol biosynthesis inhibitor that targets the 7-dehydrocholesterol Δ7-reductase (DHCR7) enzyme (IC50=13 nM). At high doses, AY 9944 also inhibits sterol Δ7-Δ8 isomerase in cultured embryos, leading to the accumulation of cholest-8-en-3β-ol[1][2][3]. Additionally, AY 9944 causes hypocholesterolemia and accumulation of 7DHC.

Peraclopone is a hypolidemic drug. It is an inhibitor of 7-Dehydrocholesterol reductase. Peraclopone potently inhibits the final step in cholesterol biosynthesis. Feeding this agent to rats leads to a rapid replacement of membrane cholesterol with its immediate precursor 7-dehydrocholesterol, and a dramatic reduction in plasma sterol concentration. Peraclopone caused a dose-dependent decrease in cholesterol and a concomitant accumulation of provitamin D3 (7-dehydrocholesterol) in the skin, which is accompanied by an increase in the plasma level of 25-hydroxyvitamin D3. Treatment with peraclopone dramatically alters membrane sterol content in many membranes including the microvillus membrane of both the jejunum and ileum. In the jejunal microvillus membrane a major change in chemical composition occurred, presumably in response to the alteration in membrane sterol. The net result was a significant decline in both the static and dynamic component of membrane fluidity.

Fenhexamid (Elevate), a sterol biosynthesis inhibitor, shows antifungal activity against the plant pathogenic fungus. Fenhexamid is used for agriculture and is present in measurable amounts in fruits and vegetables.

Fenpropidin (Ro-12-3049), a fungicide, is a specific inhibitor of sterol 14-reductase and biosynthesis.