Lovastatin-d9 is intended for use as an internal standard for the quantification of lovastatin by GC- or LC-MS. Lovastatin is an HMG-CoA reductase inhibitor that was originally isolated from A. terreus.1 It is a prodrug of its more potent metabolite, lovastatin hydroxy acid . Both competitively inhibit HMG-CoA reductase with Ki values of 1.4 and 0.6 nM for lovastatin and the open ring, hydroxy acid form, respectively.2 Lovastatin (8 mg/kg per day) reduces plasma cholesterol in dogs by 29% over a three-week period. It also suppresses TNF-induced NF-κB activation (IC50 = ~15 µM), which potentiates apoptosis in human myeloid leukemia cells.3 Formulations containing lovastatin were the first HMG-CoA reductase inhibitors to be used in the treatment of hypercholesterolemia.
1.Endo, A.The discovery and development of HMG-CoA reductase inhibitorsJ. Lipid Res.33(11)1569-1582(1992) 2.Alberts, A.W., Chen, J., Kuron, G., et al.Mevinolin: A highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agentProc. Natl. Acad. Sci. USA77(7)3957-3961(1980) 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 pathwayBiochem. Pharmacol.75(4)907-913(2008)