Simvastatin - 半岛电竞官方网址

Molecular Weight (MW)	418.57
Formula	C25H38O5
CAS No.	79902-63-9
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility(In vitro)	DMSO: 83 mg/mL (198.3 mM)
Water: <1 mg/mL
Ethanol: 83 mg/mL (198.3 mM)
Solubility(In vivo)	2% DMSO+30% PEG 300+5% Tween80+ddH2O: 10 mg/mL
Synonyms	MK-0733, MK 0733, MK0733, Zocor; Synvinolin; MK 733; Sinvacor; MK-733; MK733; Simvastatin; Chemical Name: (1S,3R,7S,8S)-8-(2-((2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate SMILES Code: C[C@H]1C=CC2=C[C@H](C)C[C@H](OC(C(C)(C)CC)=O)C2[C@H]1CC[C@@H]3C[C@@H](O)CC(O3)=O

Molecular Weight (MW)

418.57

Formula

C25H38O5

CAS No.

79902-63-9

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility(In vitro)

DMSO: 83 mg/mL (198.3 mM)

Water: <1 mg/mL

Ethanol: 83 mg/mL (198.3 mM)

Solubility(In vivo)

2% DMSO+30% PEG 300+5% Tween80+ddH2O: 10 mg/mL

Synonyms

MK-0733, MK 0733, MK0733, Zocor; Synvinolin; MK 733; Sinvacor; MK-733; MK733; Simvastatin;

Chemical Name: (1S,3R,7S,8S)-8-(2-((2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate

SMILES Code: C[C@H]1C=CC2=C[C@H](C)C[C@H](OC(C(C)(C)CC)=O)C2[C@H]1CC[C@@H]3C[C@@H](O)CC(O3)=O

In Vitro	In vitroactivity: 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. Simvastatin (1.0 μM) enhances phosphorylation of the endogenous Akt substrate endothelial nitric oxide synthase (eNOS), inhibits serum-free media undergo apoptosis and accelerates vascular structure formation. Simvastatin displays anti-inflammatory effects in vitro. Simvastatin (10 μM) reduces anti-CD3/anti-CD28 antibody-stimulated proliferation of PB-derived mononuclear cells and synovial fluid cells from rheumatoid arthritis blood, as well as IFN-γ release. Simvastatin (10 μM) suppresses cell-mediated macrophage TNF-γ release induced via cognate interactions by ~30%. Kinase Assay: For assessment of Akt protein kinase activity in vitro, substrate (2 μg histone H2B or 25 μg eNOS peptide) is incubated with Akt immunoprecipitated from cell lysate using goat polyclonal anti-Akt1 antibody. Kinase reactions are initiated following the addition of Simvastatin to a final concentration of ATP (50 μM) containing 10 μCi of 32P-γATP, dithiotreitol (1 mM), HEPES buffer (20 mM, pH 7.4), MnCl2 (10 mM), MgCl2 (10 mM). After incubation for 30 min at 30°C, phosphorylated histone H2B is visualized after SDS-PAGE (15%) and autoradiography. To estimate the extent of 32P incorporation into eNOS peptides, each reaction mixture is measured by spotting onto phosphocellulose disc filter and the amount of phosphate incorporated is measured by Cerenkov counting. The wild-type peptide sequence is 1174-RIRTQSFSLQERHLRGAVPWA-1194, and the mutant eNOS peptide is identical except that serine 1179 is substituted by alanine. Cell Assay: In mouse L-M cells (fibroblast), rat H4IIE cells (liver) and human Hep G2 cells (liver), Simvastatin inhibited cholesterol synthesis with the IC50 values of 19.3 nM, 13.3 nM and 15.6 nM, respectively.
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. Simvastatin influences inflammation independent of its effect on plasma cholesterol level. In cynomolgus monkeys consumed an atherogenic diet, Simvastatin (20 mg/kg/day) induces a 1.3-fold less macrophage content in lesions, and 2-fold less vascular cell adhesion molecule-1, interleukin-1beta, and tissue factor expression, companied by a 2.1-fold increases in lesional smooth muscle cell and collagen content.
Animal model	Dogs
Formulation & Dosage	50 mg/kg/d; p.o.
References	Drugs. 1988;36 Suppl 3:72-82; Jpn J Pharmacol. 1989 Jan;49(1):125-33; Biochim Biophys Acta. 1990 Feb 23;1042(3):365-73.

In Vitro

In vitroactivity: 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. Simvastatin (1.0 μM) enhances phosphorylation of the endogenous Akt substrate endothelial nitric oxide synthase (eNOS), inhibits serum-free media undergo apoptosis and accelerates vascular structure formation. Simvastatin displays anti-inflammatory effects in vitro. Simvastatin (10 μM) reduces anti-CD3/anti-CD28 antibody-stimulated proliferation of PB-derived mononuclear cells and synovial fluid cells from rheumatoid arthritis blood, as well as IFN-γ release. Simvastatin (10 μM) suppresses cell-mediated macrophage TNF-γ release induced via cognate interactions by ~30%.

Kinase Assay: For assessment of Akt protein kinase activity in vitro, substrate (2 μg histone H2B or 25 μg eNOS peptide) is incubated with Akt immunoprecipitated from cell lysate using goat polyclonal anti-Akt1 antibody. Kinase reactions are initiated following the addition of Simvastatin to a final concentration of ATP (50 μM) containing 10 μCi of 32P-γATP, dithiotreitol (1 mM), HEPES buffer (20 mM, pH 7.4), MnCl2 (10 mM), MgCl2 (10 mM). After incubation for 30 min at 30°C, phosphorylated histone H2B is visualized after SDS-PAGE (15%) and autoradiography. To estimate the extent of 32P incorporation into eNOS peptides, each reaction mixture is measured by spotting onto phosphocellulose disc filter and the amount of phosphate incorporated is measured by Cerenkov counting. The wild-type peptide sequence is 1174-RIRTQSFSLQERHLRGAVPWA-1194, and the mutant eNOS peptide is identical except that serine 1179 is substituted by alanine.

Cell Assay: In mouse L-M cells (fibroblast), rat H4IIE cells (liver) and human Hep G2 cells (liver), Simvastatin inhibited cholesterol synthesis with the IC50 values of 19.3 nM, 13.3 nM and 15.6 nM, respectively.

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. Simvastatin influences inflammation independent of its effect on plasma cholesterol level. In cynomolgus monkeys consumed an atherogenic diet, Simvastatin (20 mg/kg/day) induces a 1.3-fold less macrophage content in lesions, and 2-fold less vascular cell adhesion molecule-1, interleukin-1beta, and tissue factor expression, companied by a 2.1-fold increases in lesional smooth muscle cell and collagen content.

Animal model

Dogs

Formulation & Dosage

50 mg/kg/d; p.o.

References

Drugs. 1988;36 Suppl 3:72-82; Jpn J Pharmacol. 1989 Jan;49(1):125-33; Biochim Biophys Acta. 1990 Feb 23;1042(3):365-73.

CAS NO:	79902-63-9
规格:	≥98%

包装	价格(元)
50mg	电议
100mg	电议
250mg	电议
500mg	电议
1g	电议
2g	电议