(3S,5S)-Atorvastatin

Atorvastatin is an HMG-CoA reductase inhibitor (IC₅₀ = 154 nM) that is effective against hypercholesterolemia and certain dyslipidemias.^1,2,3 Atorvastatin can exist in four optical forms, with the 3R,5R enantiomer displaying the greatest activity against HMG-CoA reductase. (3S,5S)-Atorvastatin is an enantiomer of atorvastatin that has little or no inhibitory activity against HMG-CoA reductase.⁴ It also differs from other atorvastatin enantiomers in cytotoxicity, activation of the pregnane X receptor, and induction of cytochrome P450 isoforms.^4,5

1.Dart, A., Jerums, G., Nicholson, G., et al.A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemiaAm. J. Cardiol.80(1)39-44(1997) 2.Group, T.D.A.L.I.S.The effect of aggressive versus standard lipid lowering by atorvastatin on diabetic dyslipidemia. The DALI study: A double-blind, randomized, placebo-controlled trial in patients with type 2 diabetes and diabetic dyslipidemiaDiabetes Care24(8)1335-1341(2001) 3.van Dam, M., Zwart, M., de Beer, F., et al.Long term efficacy and safety of atorvastatin in the treatment of severe type III and combined dyslipidaemiaHeart88(3)234-238(2002) 4.Kocarek, T.A., Dahn, M.S., Cai, H., et al.Regulation of CYP2B6 and CYP3A expression by hydroxymethylglutaryl coenzyme A inhibitors in primary cultured human hepatocytesDrug Metab. Dispos.30(12)1400-1405(2002) 5.Korhonova, M., Doricakova, A., and Dvorak, Z.Optical Isomers of Atorvastatin, Rosuvastatin and Fluvastatin Enantiospecifically Activate Pregnane X Receptor PXR and Induce CYP2A6, CYP2B6 and CYP3A4 in Human HepatocytesPLoS One10(9)(2015)