An HMG-CoA reductase inhibitor
Rosuvastatin Calcium (Rosuvastatin hemicalcium) is a competitive HMG-CoA reductase inhibitor with an IC50 of 11 nM[1]. Rosuvastatin Calcium potently blocks human ether-a-go-go related gene (hERG) current with an IC50 of 195 nM, delayed cardiac repolarization, and thereby prolonged action potential durations (APDs) and corrected QT interval (QTc) intervals[2]. Rosuvastatin Calcium reduces the expression of the mature hERG and the interaction of heat shock protein 70 (Hsp70) with the hERG protein. Rosuvastatin Calcium is very effective in lowering low-density lipoprotein (LDL) cholesterol, triglycerides, and C-reactive protein levels[3].
Rosuvastatin Calcium (10 mg/kg, intraperitoneal) prolonges QTc in conscious and unrestraines guinea pigs from 201 ± 1 to 210 ± 2 ms.
参考文献:
[1]. Watanabe, M., et al., Synthesis and biological activity of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates, a novel series of HMG-CoA reductase inhibitors. Bioorg Med Chem, 1997. 5(2): p. 437-44.
[2]. Carswell C.I., et al. Rosuvastatin. Drugs, 2002. 62(14): p. 2075-85; discussion 2086-7.
[3]. Plante I, et al. Rosuvastatin blocks hERG current and prolongs cardiac repolarization. J Pharm Sci. 2012 Feb;101(2):868-78.
[4]. Feng PF, et al. Intracellular Mechanism of Rosuvastatin-Induced Decrease in Mature hERG Protein Expression on Membrane. Mol Pharm. 2019 Apr 1;16(4):1477-1488.
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