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
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  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

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• 动物研究
  剂量	Rat: 1 mg/kg - 20 mg/kg[3] (i.g.), 10 mg/kg - 40 mg/kg[4] (p.o.) Mice: 10 mg/kg - 100 mg/kg[5] (i.g.)
  给药途径	i.g., p.o.

• 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 ... more >> GSK Investigational Site Austin, Texas, United States, 78744 Collapse <<
  NCT00351286	Peripheral Arterial Disease ... more >> Intermittent Claudication Collapse <<	Phase 2	Unknown	-	Russian Federation ... more >> 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 Collapse <<
  NCT01097785	Heart Failure	Not Applicable	Completed	-	United States, Missouri ... more >> University of Missouri Columbia, Missouri, United States, 65212 Collapse <<

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