产品说明书

Simvastatin

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Chemical Structure| 79902-63-9 同义名 : MK 733;SVA
CAS号 : 79902-63-9
货号 : A198975
分子式 : C25H38O5
纯度 : 98%
分子量 : 418.566
MDL号 : MFCD00072007
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(119.46 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 100 mg/mL(238.91 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

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

生物活性
描述 The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA )reductase is the rate-limiting step in cholesterol synthesis, converting HMG-CoA to mevalonic acid, which through a series of additional steps is converted to cholesterol. Simvastatin is a long-established HMG-CoA reductase inhibitor.[4].Simvastatin suppresses cholesterol synthesis in mouse L-M cell, rat H4II E cell, and human Hep G2 cell with IC50s of 19.3 nM, 13.3 nM and 15.6 nM, respectively[5]. Simvastatin causes 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[6]. Simvastatin shows anti-inflammatory effects, 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 at 10 μM. Simvastatin (10 μM) also blocks cell-mediated macrophage TNF-γ release induced via cognate interactions[7]. Simvastatin (5 μM) significantly reduces the expression of ABCA1 in astrocytes and neuroblastoma cells, the expression of apolipoprotein E in astrocytes, and increases cyclin-dependent kinase 5 and glycogen synthase kinase 3β expression in SK-N-SH cells[8].
作用机制 Simvastatin acts by decreasing cholesterol synthesis and by increasing low density lipoprotein (LDL) catabolism via increased LDL receptor activity. It also produces a beneficial moderate decrease in plasma triglycerides and a small, although significant, increase in high density lipoprotein (HDL)-cholesterol.[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HEK293 cells Function assay Inhibition of OATP1B1 (unknown origin) expressed in HEK293 cells using estradiol-17beta-glucuronide substrate, IC50=4.4 μM 22587986
HepG2 cells Function assay In vitro inhibitory activity was evaluated on cholesterol biosynthesis in HepG2 cells, IC50=0.04 μM 14741258
human A549 cells Cytotoxic assay 72 h Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50=16.3 μM 23570542
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00605449 Type 2 Diabetes Mellitus Phase 1 Completed - United States, Texas ... 展开 >> GSK Investigational Site Austin, Texas, United States, 78744 收起 <<
NCT00351286 Peripheral Arterial Disease ... 展开 >> Intermittent Claudication 收起 << Phase 2 Unknown - Russian Federation ... 展开 >> Municipal Healthcare Institution, Gatchina Central District Hospital Gatchina, Russia, Russian Federation, 188300 Russian State Medical University at Filatov City Hospital #15 Moscow, Russia, Russian Federation, 111539 Vishnevsky Institute of Surgery, Russian Medical Academy of Science Moscow, Russia, Russian Federation, 113811 Municipal Prophylaxis and Treatment Institution, City Hospital #13 N. Novgorod, Russia, Russian Federation, 603018 Municipal Medical Institution City Hospital #1 of Saratov Saratov, Russia, Russian Federation, 410056 St. Petersburg State Healthcare Institution, Research for Emergency Medical Care St. Petersburg, Russia, Russian Federation, 192242 St. Petersburg State Healthcare Institution, Hospital #2 St. Petersburg, Russia, Russian Federation, 194354 St. Petersburg State Healthcare Institution, Hospital #26 St. Petersburg, Russia, Russian Federation, 196247 State Educational Institution of Higher Professional Education St. Petersburg, Russia, Russian Federation, 197089 St. Petersburg State Healthcare Institution, Pokrovskaya Hospital St. Petersburg, Russia, Russian Federation, 199106 收起 <<
NCT01097785 Heart Failure Not Applicable Completed - United States, Missouri ... 展开 >> University of Missouri Columbia, Missouri, United States, 65212 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.39mL

0.48mL

0.24mL

11.95mL

2.39mL

1.19mL

23.89mL

4.78mL

2.39mL
参考文献

[1] P A Todd,et al. Simvastatin. A review of its pharmacological properties and therapeutic potential in hypercholesterolaemia. Drugs.1990 Oct;40(4):583-607.

[2] Jennifer G Robinson, Simvastatin: present and future perspectives. Expert Opin Pharmacother. 2007 Sep;8(13):2159-27.

[3] P A Todd,et al. Simvastatin. A review of its pharmacological properties and therapeutic potential in hypercholesterolaemia. Drugs.1990 Oct;40(4):583-607.

[4]Kureishi, Y., et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med, 2000. 6(9): p. 1004-10.

[5]Leung BP, et al. A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol. 2003 Feb 1;170(3):1524-30.

[6]Weijiang Dong, et al. Differential effects of simvastatin and CS-514 on expression of Alzheimer’s disease-related genes in human astrocytes and neuronal cells. J Lipid Res. 2009 Oct; 50(10): 2095-2102.