| Description | Simvastatin (MK 733) is an HMG-CoA reductase inhibitor (Ki=0.2 nM) with oral activity. Simvastatin has hypolipidemic activity, inhibits hepatic production of cholesterol, and is also used for the prevention of cardiovascular disease. |
| In vitro | 方法：BCa 细胞 5637、EJ 和 T24 用含 Simvastatin (0.5-40 µM) 处理 48 h，使用 MTT assay 检测细胞活力。结果：Simvastatin 以剂量依赖的方式显著抑制了三种 BCa 细胞的存活 。[1]方法：人成纤维细胞 SAEC 和四种肿瘤细胞 MCF7、HepG2、NCH、NCI 用 Simvastatin (20 µM) 处理 72 h，使用 TUNEL 检测细胞凋亡情况。结果：Simvastatin 可诱导不同类型的人肿瘤细胞发生凋亡，但不诱导 SAEC 细胞发生明显的凋亡。[2] |
| In vivo | 方法：为研究体内活性，将 Simvastatin (60 mg/kg，aqueous 2% DMSO+30% PEG 400+5% Tween 80) 灌胃给药给 C57BL/6J 小鼠，每天一次，持续六周，给予 CF 饮食。结果：Simvastatin 治疗使血清胆固醇水平降低了 18%，视网膜胆固醇和脂蛋白胆固醇含量分别降低了 24% 和 21%。[3]方法：为检测体内抗肿瘤活性，将 Simvastatin (5-50 mg/kg in methylcellulose) 灌胃给药 BALB/c nu/nu 小鼠，每天一次，持续三天。随后将结直肠癌细胞 COLO205 皮下接种到小鼠右侧。结果：Simvastatin 通过诱导肿瘤细胞凋亡和抑制肿瘤血管生成抑制异种移植小鼠模型中的肿瘤生长。[4] |
| Target activity | HMG-CoA reductase:0.1-0.2 nM(Ki) |
| Synonyms | 辛伐他汀, MK-0733, MK 733 |
| molecular weight | 418.57 |
| Molecular formula | C25H38O5 |
| CAS | 79902-63-9 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | Ethanol: 31.4 mg/mL (75 mM) DMSO: 50 mg/mL (119.45 mM) |
| References | 1. Wang G, et al. Simvastatin induces cell cycle arrest and inhibits proliferation of bladder cancer cells via PPARγ signalling pathway. Sci Rep. 2016 Oct 25;6:35783. 2. Spampanato C, et al. Simvastatin inhibits cancer cell growth by inducing apoptosis correlated to activation of Bax and down-regulation of BCL-2 gene expression. Int J Oncol. 2012 Apr;40(4):935-41. 3. Mast N, et al. Retinal Cholesterol Content Is Reduced in Simvastatin-Treated Mice Due to Inhibited Local Biosynthesis Albeit Increased Uptake of Serum Cholesterol. Drug Metab Dispos. 2018 Nov;46(11):1528-1537. 4. Cho SJ, et al. Simvastatin induces apoptosis in human colon cancer cells and in tumor xenografts, and attenuates colitis-associated colon cancer in mice. Int J Cancer. 2008 Aug 15;123(4):951-7. 5. Ishida F, et al. Biochim Biophys Acta, 1990, 1042(3), 365-373. 6. Liu Z, et al. Pretreatment Donors after Circulatory Death with Simvastatin Alleviates Liver Ischemia Reperfusion Injury through a KLF2-Dependent Mechanism in Rat. Oxid Med Cell Longev. 2017;2017:3861914. 7. Wei Y H, Liao S L, Wang S H, et al. Simvastatin and ROCK Inhibitor Y-27632 Inhibit Myofibroblast Differentiation of Graves’ Ophthalmopathy-Derived Orbital Fibroblasts via RhoA-Mediated ERK and p38 Signaling Pathways[J]. Frontiers in Endocrinology. 2021, 11: 1109. 8. Wei Y H, Liao S L, Wang C C, et al. Simvastatin Inhibits CYR61 Expression in Orbital Fibroblasts in Graves’ Ophthalmopathy through the Regulation of FoxO3a Signaling[J]. Mediators of Inflammation. 2021, 2021. 9. Tang Y, Fang G, Guo F, et al. Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer[J]. Cancer Cell. 2020, 38(1): 115-128. e9. |
| Kinase | 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 reaction components 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. |