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Simvastatin (Zocor)

现货
Catalog No.
A8522
HMGCR(HMG-CoA还原酶)抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
50mg
¥ 840.00
现货
250mg
¥ 2,570.00
Ship with 10-15 days

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Background

Simvastatin (SIM), a lactone, is white, crystalline, nonhygroscopic and powdery, practically insoluble in water (30 mcg/ml), and 0.1 (N) HCl (60 mcg/ml). Its precursor is a fermentation product of Aspergillus terreus. It is used for treating coronary heart disease, hyperlipidemia, hypercholesterolemia, atherosclerosis and stroke [1] [2]. SIM is biologically inactive. Oral ingestion hydrolyzed it into the β-hydroxyacid form which is an inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase [2]. In human lung microvascular endothelial cells, it increased the amount of endothelial nitric oxide synthase mRNA [3]. Simvastatin had anti-cancer properties [1]. Its IC50 to inhibit P-glycoprotein is 9 μM [4].

HMG CoA reductase catalyses an early rate-limiting step in the biosynthesis of cholesterol [2].

In both cell lines HepG2 and Huh7, both doses of simvastatin (32 and 64 μM) had a significant inhibitory effect on tumor cell growth as compared to controls (p<0.05). This effect was time-dependent, a simvastatin pre-treatment for 48 h or 72 h significantly reduced cell growth as compared to 24 h pre-incubation (p<0.05). Simvastatin treatment for 48 or 72 h made HepG2 cells exhibit downregulation of CDK1, CDK2, CDK4 and cyclins D1 and E as compared to control tumor cells. Simvastatin treatment for 24, 48 and 72 h made relative expression of cyclin-dependent kinase inhibitors p19 and p27 enhance as compared to control tumor cells [1].

In patients with polygenic hypercholesterolemia and allocated to diet plus 20 mg/day simvastatin for 8 weeks, total cholesterol (-27%), low density lipoproteincholesterol (-33%), and monocyte expression of TNF (-49%) and IL-1( (-35%) significantly decreased (p<0.02) [5].

References:
[1].  Borna Relja, Frank Meder, Kerstin Wilhelm, et al. Simvastatin inhibits cell growth and induces apoptosis and G0/G1 cell cycle arrest in hepatic cancer cells. International Journal of Molecular Medicine, 2010, 26:735-741.
[2].  Dipika Mandal, Probir Kumar Ojha, Bankim Chandra Nandy, et al. Effect of Carriers on Solid Dispersions of Simvastatin (Sim): Physico-Chemical Characterizations and Dissolution Studies. Der Pharmacia Lettre, 2010, 2(4):47-56.
[3].  Ji-Hyun Lee, Dong-Soon Lee, Eun-Kyung Kim, et al. Simvastatin Inhibits Cigarette Smoking–induced Emphysema and Pulmonary Hypertension in Rat Lungs. American Journal of Respiratory and Critical Care Medicine, 2005, 172: 987-993.
[4].  C. Bradley Hare, Mai P. Vu, Carl Grunfeld, et al. Simvastatin-Nelfinavir Interaction Implicated in Rhabdomyolysis and Death. Clinical Infectious Diseases, 2002, 35:e111–2.
[5].  Domenico Ferro, Sandro Parrotto, Stefania Basili, et al. Simvastatin Inhibits the Monocyte Expression of Proinflammatory Cytokines in Patients With Hypercholesterolemia. Journal of the American College of Cardiology, 2000, 36(2): 427–431.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt418.6
Cas No.79902-63-9
FormulaC25H38O5
Solubility≥20.95mg/mL in DMSO
Chemical Name[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] 2,2-dimethylbutanoate
SDFDownload SDF
Canonical SMILESCCC(C)(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

小鼠L-M细胞(成纤维细胞)、大鼠H4IIE细胞(肝)以及人Hep G2细胞(肝)

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

13.3、15.6或19.3 nM

实验结果

在小鼠L-M细胞(成纤维细胞)、大鼠H4IIE细胞(肝)以及人Hep G2细胞(肝)中,Simvastatin抑制胆固醇合成,其IC50值分别为19.3 nM、13.3 nM和15.6 nM。

动物实验 [1]:

动物模型

给药剂量

50 mg/kg/d;口服给药;每日1次,持续1个月

实验结果

与L654,969组相比,Simvastatin组的血清胆固醇浓度相对较低。然而,Simvastatin和Lovastatin具有相当的降胆固醇作用。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Slater EE, MacDonald JS. Mechanism of action and biological profile of HMG CoA reductase inhibitors. A new therapeutic alternative. Drugs. 1988;36 Suppl 3:72-82.

质量控制

化学结构

Simvastatin (Zocor)