美伐他汀作用机制 - Medchemexpress - MCE中国

1、Product Data SheetMevastatinCat. No.: HY-17408CAS No.: 73573-88-3分式: CHO分量: 390.51作靶点: HMG-CoA Reductase (HMGCR); Bacterial; Autophagy; Apoptosis作通路: Metabolic Enzyme/Protease; Anti-infection; Autophagy; Apoptosis储存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from l

2、ight)溶解性数据体外实验 DMSO : 25 mg/mL (64.02 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 2.5608 mL 12.8038 mL 25.6075 mL5 mM 0.5122 mL 2.5608 mL 5.1215 mL10 mM 0.2561 mL 1.2804 mL 2.5608 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 mont

3、h (protect from light)。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubilit

4、y: 2.5 mg/mL (6.40 mM); Clear solution此案可获得 2.5 mg/mL (6.40 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.40 mM); Clear solution此案可获得 2.5 mg/mL

5、 (6.40 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。Page 1 of 2 www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.40 mM); Clear solution此案可获得 2.5 mg/mL (6.40 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO

6、储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Mevastatin (Compactin)第个属于他汀类的 HMG-CoA 还原酶抑制剂。Mevastatin 种降脂药，可诱导细胞凋亡，将癌细胞阻滞在 G0/G1 期。Mevastatin 还可以增加内型氧化氮合酶 (eNOS) 的 mRNA 和蛋质平。Mevastatin 具有抗肿瘤活性，并可于管疾病的研究。IC & Target HMG-CoA reductase12Apoptosis1体外研究Mevastatin (0-128 M; 5 days; Caco-2 cells) treatment c

7、auses a dose-dependent decrease in cell number1.Mevastatin (32-128 M; 24-72 hours; Caco-2 cells) treatment causes an early G0/G1 phase and a late G2/M phase cellcyclr arrest1.Mevastatin (32-128 M; 72 hours; Caco-2 cells) treatment causes a down-regulation of cyclin-dependent kinases (cdk)4 and cdk 6

8、 as well as cyclin D1, while cdk 2 and cyclin E protein levels remained unchanged. Cell cycle inhibitors p21and p27 are significantly upregulated by Mevastatin1.Mevastatin (16-256 M; Caco-2 cells) treatment induces apoptosis in a dose-dependent manner1.Treatment of Neuro2a cells with mevastatin for

9、24 hours induced neurite outgrowth associated with up-regulation ofthe neuronal marker protein NeuN. Mevastatin triggers phosphorylation of the key kinases epidermal growth factorreceptor (EGFR), ERK1/2, and Akt/protein kinase B. Inhibition of EGFR, PI3K, and the mitogen-activated protein kinasecasc

10、ade blocks Mevastatin-induced neurite outgrowth4.Cell Viability Assay2Cell Line: Caco-2 cellsConcentration: 0 M, 8 M, 16 M, 32 M, 64 M, 128 MIncubation Time: 5 daysResult: Caused a dose-dependent decrease in cell number.Cell Cycle Analysis2Cell Line: Caco-2 cellsConcentration: 32 M, 64 M, 128 MIncub

11、ation Time: 24 hours, 48 hours, 72 hoursResult: Caused a dose-dependent increase of cells in G0/G1 and G2/M phases of the cellcycle.Western Blot Analysis2Cell Line: Caco-2 cellsConcentration: 32 M, 64 M, 128 MPage 2 of 3 www.MedChemEIncubation Time: 72 hoursResult: Resulted in a down-regulation of c

12、yclin-dependent kinases (cdk) 4 and cdk 6 as wellas cyclin D1.体内研究 Mevastatin (2-20 mg/kg; delivered via ALZET miniosmotic pumps; daily; for 7, 14, or 28 days; wild-type 129-SV/eVTAcBr male mice and eNOS-deficient male mice) treatment increases levels of endothelial nitric oxide synthase (eNOS) mRNA

13、 and protein, reduces infarct size, and improves neurological deficits in a dose- and time-dependentmanner2.The topical infusion of Mevastatin (2.5 pmol/hr) increases bone mass (MRL/MpJ mouse) of isografted bone byincreasing bone turnover and, at least in part, by promoting the expression of bone mo

14、rphogenetic protein-2 (BMP-2) mRNA and receptor activator of NF-B ligand (RANKL) mRNA3.Animal Model: Wild-type 129-SV/eVTAcBr male mice and eNOS-deficient male mice (18-22 g) withthe filament model2Dosage: 2 mg/kg or 20 mg/kgAdministration: Delivered via 7- or 14-day ALZET miniosmotic pumps implante

15、d subcutaneously;daily; for 7, 14, or 28 daysResult: Increased levels of endothelial nitric oxide synthase (eNOS) mRNA and protein,reduced infarct size, and improved neurological deficits in a dose- and time- dependent manner.户使本产品发表的科研献 Cell Death Dis. 2020 Jan 13;11(1):25. Front Cell Dev Biol. 202

16、0 May. PLoS Negl Trop Dis. 2019 Aug 20;13(8):e0007681. Eur Res J. March 20, 2018.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Sugazaki M, Hirotani H, Echigo S, et al. Effects of mevastatin on grafted bone in MRL/MpJ mice. Connect Tissue Res. 2010 Apr;51(2):105-12.

17、2. Evangelopoulos ME, Weis J, Krttgen A. Mevastatin-induced neurite outgrowth of neuroblastoma cells via activation of EGFR. J Neurosci Res. 2009Jul;87(9):2138-44.3. Wchtershuser A, et al. HMG-CoA reductase inhibitor mevastatin enhances the growth inhibitory effect of butyrate in the colorectal carcinoma cell lineCaco-2. Carcinogenesis. 2001 Jul;22(7):1061-7.4. Amin-Hanjani S, Stagliano NE, Yamada M, et al. Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitricoxide synthase in mice. Strok