Hydroxymethylglutaryl-coenzyme A (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 Fluvastatin acts as a competitive inhibitor of HMG-CoA reductase with respect to binding of the substrate HMG-CoA (Ki = 0.3 nM) but not with respect to binding of NADPH.2,3 It is marketed under the trade name Lescol for the treatment of hypercholesterolemia in the prevention of cardiovascular disease. When fluvastatin was administered in a clinical trial to patients undergoing percutaneous coronary intervention, LDL cholesterol levels were reduced by 27% after six weeks of treatment with a dose of 40 mg/kg twice a day compared to placebo.4
1
Tobert, J.A. Lovastatin and beyond: The history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov2517-526(2003).
2
Istvan, E.S., and Deisenhofer, J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science2921160-1164(2001).
3
Corsini, A., Maggi, F.M., and Catapano, A.L. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res31(1)9-27(1995).
4
Serruys, P.W.J.C., de Feyter, P., Macaya, C., et al. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: A randomized controlled trial. JAMA287(24)3215-3222(2002).
Formal Name
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2-yl]-3,5-dihydroxy-6-heptenoic acid, sodium salt
CAS Number
93957-55-2
Molecular Formula
C24H25FNO4 · Na
Formula Weight
433.5
Formulation
A crystalline solid
Purity
≥98%
λmax
233, 305 nm
Stability
2 years
Storage
-20°C
Shipping
Room temperature
in continental US; may vary elsewhere
Tobert, J.A. Lovastatin and beyond: The history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov2517-526(2003).
Corsini, A., Maggi, F.M., and Catapano, A.L. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res31(1)9-27(1995).
Serruys, P.W.J.C., de Feyter, P., Macaya, C., et al. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: A randomized controlled trial. JAMA287(24)3215-3222(2002).
Istvan, E.S., and Deisenhofer, J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science2921160-1164(2001).