Simvastatin (MK-0733, MK 733) is a competitive inhibitor of HMG-CoA reductase with Ki of 0.1-0.2 nM in cell-free assays. Simvastatin induces ferroptosis, mitophagy, autophagy and apoptosis. Simvastatin inhibits exosome release.
Prior to use in cell assays, Simvastatin needs to be activated by NaOH in EtOH treatment. Simvastatin inhibits cholesterol synthesis in mouse L-M cell (fibroblast), rat H4II E cell (liver), and human Hep G2 cell (liver) with IC50 of 19.3 nM, 13.3 nM and 15.6 nM, respectively. Simvastatin treatment leads to a dose-dependent increase in serine 473 phosphorylation of Akt within 30 minutes, with maximal phosphorylation occurring at 1.0 µM.
In vivo, Simvastatin orally administration inhibits the conversion of radiolabeled acetate to cholesterol with IC50 of 0.2 mg/kg. Simvastatin (4 mg/day) orally administration for 13 weeks to rabbits fed an atherogenci cholesterol-rich diet, returns the cholesterol-induced increases in total cholesterol, LDL-cholesterol and HDL-cholesterol to normal level. Simvastatin (6 mg/kg) produces an increase in LDL receptor-dependent binding and increases the number of hepatic LDL receptors in rabbits fed a diet containing 0.25% cholesterol.
Activation of simvastatin
Simvastatin needs to be activated by opening of the lactone ring before use in cell culture. Briefly, eight milligrams of simvastatin (0.019 mM) were dissolved in 0.2 ml of 100% ethanol, with subsequent addition of 0.3 ml of 0.1 N NaOH. The solution was heated at 50°C for 2 h in a sand bath and then neutralized with HCl to pH 7.2. The resulting solution was brought to a final volume (1 ml) with distilled water, and aliquots were stored at −80°C until use.
Molecules. 2022 Jul 31;27(15):4894.
Metagenomics Approach to the Intestinal Microbiome Structure and Abundance in High-Fat-Diet-Induced Hyperlipidemic Rat Fed with (−)-Epigallocatechin-3-Gallate
Simvastatin (MK 733) purchased from AbMole
J Funct Foods. 2022 Mar;Volume 90, 104998.
Epigallocatechin-3-gallate + L-theanine/β-cyclodextrin inclusion complexes enhance epigallocatechin-3-gallate bioavailability and its lipid-lowering and weight loss effects
Simvastatin (MK 733) purchased from AbMole
Chem Res. 2021 Oct 18.
Comprehensive Analysis of Differential Gene Expression Profile via RNA Sequencing in the Human Ovarian Cancer SKOV3 Cells Treated with Simvastatin
Simvastatin (MK 733) purchased from AbMole
Pak J Pharm Sci. 2016 May;29(3 Suppl):1043-51.
Chromatographic resolution of drug analogues: 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors (statins)
Simvastatin (MK 733) purchased from AbMole
Molecular Weight | 418.57 |
Formula | C25H38O5 |
CAS Number | 79902-63-9 |
Solubility (25°C) | DMSO 80 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[2] Tanzeela A Fattah, et al. Synthetic Approaches Towards Antihypercholesterolemic Drug Simvastatin
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