美伐他汀作用機制 - Medchemexpress - MCE中國

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

2、ight)溶解性數(shù)據(jù)體外實驗 DMSO : 25 mg/mL (64.02 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液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請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 mont

3、h (protect from light)。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubilit

4、y: 2.5 mg/mL (6.40 mM); Clear solution此案可獲得 2.5 mg/mL (6.40 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.40 mM); Clear solution此案可獲得 2.5 mg/mL

5、 (6.40 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。Page 1 of 2 www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.40 mM); Clear solution此案可獲得 2.5 mg/mL (6.40 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO

6、儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Mevastatin (Compactin)第個屬于他汀類的 HMG-CoA 還原酶抑制劑。Mevastatin 種降脂藥，可誘導(dǎo)細(xì)胞凋亡，將癌細(xì)胞阻滯在 G0/G1 期。Mevastatin 還可以增加內(nèi)型氧化氮合酶 (eNOS) 的 mRNA 和蛋質(zhì)平。Mevastatin 具有抗腫瘤活性，并可于管疾病的研究。IC & Target HMG-CoA reductase12Apoptosis1體外研究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.體內(nèi)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.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) 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