HMG-CoA reductase is the rate-limiting enzyme in the cholesterol biosynthetic pathway and the target of the “statin” class of cholesterol-lowering drugs.1 Mevastatin is a HMG-CoA reductase inhibitor that was initially isolated from the mold Pythium ultimum. It inhibits HMG-CoA reductase in a reversible and competitive manner with a Ki value of 1 nM for the open ring acid form of the molecule.2 During a 24 week study period, a dose of 30 mg/day mevastatin reduced plasma LDL-cholesterol approximately 29% in patients with familial hypercholesterolemia.2 Mevastatin also suppresses TNF-induced NF-κB activation (IC50 = ~17 µM), which potentiates apoptosis in human myeloid leukemia cells and thus, may be useful in treating cancer.3
1
Tobert, J.A. Lovastatin and beyond: The history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov2517-526(2003).
2
Endo, A. The discovery and development of HMG-CoA reductase inhibitors. J Lipid Res331569-1582(1992).
3
Ahn, K.S., Sethi, G., and Aggarwal, B.B. Reversal of chemoresistance and enhancement of apoptosis by statins through down-regulation of the NF-κB pathway. Biochem Pharmacol75907-913(2008).
Ahn, K.S., Sethi, G., and Aggarwal, B.B. Reversal of chemoresistance and enhancement of apoptosis by statins through down-regulation of the NF-κB pathway. Biochem Pharmacol75907-913(2008).
Tobert, J.A. Lovastatin and beyond: The history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov2517-526(2003).
Endo, A. The discovery and development of HMG-CoA reductase inhibitors. J Lipid Res331569-1582(1992).
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