HMG-CoA reductase inhibitor
Rosuvastatin Calcium is a competitive inhibitor of HMG-CoA reductase with IC50 of 11 nM in a cell-free assay.
Rosuvastatin calcium 10mM (1mL in DMSO)
£120.00
SKU: BSV-S2169-DMSO
Target: HMG-CoA reductase
Chemical name: calcium (3R,5S,E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethan-3-ylsulfonamido)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoate
Formula: C22H28FN3O6S.1/2Ca
Molecular weight: 500.57
Purity: 99.78 %
Solubility: 100 mg/mL (DMSO) warmed with 50ºC water bath
Size: 10mM (1mL in DMSO)
Storage: 3 years -20°C powder, 2 years -80°C in solvent
In vitro: Rosuvastatin is relatively hydrophilic and is highly selective for hepatic cells; its uptake is mediated by the liver-specific organic anion transporter OATP-C. Rosuvastatin is a high-affinity substrate for OATP-C with apparent association constant of 8.5 μM. [1] Rosuvastatin inhibits cholesterol biosynthesis in rat liver isolated hepatocytes with IC50 of 1.12 nM. Rosuvastatin causes approximately 10 times greater increase of mRNA of LDL receptors than pravastatin. [2] Rosuvastatin (100 μM) decreases the extent of U937 adhesion to TNF-α-stimulated HUVEC. Rosuvastatin inhibits the expressions of ICAM-1, MCP-1, IL-8, IL-6, and COX-2 mRNA and protein levels through inhibition of c-Jun N-terminal kinase and nuclear factor-kB in endothelial cells. [3]
In vivo:
Rosuvastatin is efficient on reducing plasma liquids. Rosuvastatin (3 mg/kg) daily administration for 14 days decreases plasma cholesterol levels by 26% in male beagle dogs with normal cholesterol levels. In cynomolgus monkeys, Rosuvastatin decreases plasma cholesterol levels by 22% [2] Rosuvastatin (20 mg/kg/day) administration for 2 weeks, significantly reduces very low-density lipoproteins (VLDL) in diabetes mellitus rats induced by Streptozocin. [4] Rosuvastatin shows antiatherothromhotic effects in vivo. Rosuvastatin (1.25 mg/kg) significantly inhibits thrombin-induced transmigration of monocvtes across mesenteric venules via inhibition of the endothelial cell surface expression of P-selectin, and increases the basal rate of nitric oxide in aortic segments by 2-fold times. [5] Rosuvastatin (20 mg/kg) inhibits ROS production, normalizes NO-dependent endothelial function and reduces platelet activation in diabetic rats induced by Streptozocin. [6] Rosuvastatin displays cardioprotective effects in vivo. Rosuvastatin (80 mg) is shows to decrease infarct size and improve cardiac mechanical function after ischemia/reperfusion in animal model. The cardioprotective properties of Rosuvastatin may be due to the improvement of coronary blood flow, decrease in resistance of coronary arteries mediated by enhanced eNOS expression, and the subsequent increase in the production of vascular endothelial NO. [7] Rosuvastatin (2.0 mg/kg) attenuates left ventricular hypertrophy produced by transaortic constriction in mice through regulation of Racl protein and NADPH oxidase activities. [8]
References:
[1] Schneck DW, et al. Clin Pharmacol Ther, 2004, 75(5), 4554-63.
[2] Watanabe M, et al. Bioorg Med Chem, 1997, 5(2), 437-444.
[3] Kim YS, et al. J Cardiovasc Pharmacol, 2007, 49(6), 376-383.
[4] Carswell CI, et al. Drugs, 2002, 62(14), 2075-2085
[5] Stalker TJ, et al. Br J Pharmacol, 2001, 133(3), 406-412.
[6] Sch?fer A, et al. Biochem Pharmacol, 2007, 73(9), 1367-1375.
[7] Bulhak AA, et al. Acta Physiol Scand, 2005, 183(2), 151-159.
[8] Custodis F, et al. Cardiovasc Res, 2006 Jul 15, 71(2), 342-351.
[9] Dansette PM, et al. Exp Toxicol Pathol, 2000, 52(2), 145-148.