伏瑞斯特作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetVorinostatCat. No.: HY-10221CAS No.: 149647-78-9分式: CHNO分量: 264.32作靶點: HDAC; Autophagy; Mitophagy; Filovirus作通路: Cell Cycle/DNA Damage; Epigenetics; Autophagy; Anti-infection儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL (378.33 mM)

2、* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 3.7833 mL 18.9165 mL 37.8329 mL5 mM 0.7567 mL 3.7833 mL 7.5666 mL10 mM 0.3783 mL 1.8916 mL 3.7833 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 month。-80C 儲存時，請在 6 個內(nèi)

3、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% salineSolubility: 2.5 mg/mL (9.46 mM); Clear solution此

4、案可獲得 2.5 mg/mL (9.46 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 (9.46 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (9.46 mM，飽和度未知

5、) 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。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (9.46 mM); Clear solution此案可獲得 2.5 mg/mL (9.46 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 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY

6、物活性 Vorinostat (SAHA)種有效的，可服的 HDAC1，HDAC2，HDAC3 (Class I)，HDAC7 (Class II) 和 Class IV(HDAC11) 的抑制劑，對 HDAC1/3 的 ID50 值分別為 10 nM 和 20 nM。Vorinostat 可以誘導(dǎo)細(xì)胞凋亡 (apoptosis)。Vorinostat 還 種類乳頭瘤病毒 (HPV)-18 DNA 擴(kuò)增的有效抑制劑。IC & Target HDAC1 HDAC3 HDAC2 HDAC710 nM (ID50) 20 nM (ID50)HDAC11 Autophagy Mitophagy體外研究

7、 Vorinostat efficiently suppresses MES-SA cell growth at a low dosage (3 M) already after 24 hours treatment. HDACsclass I (HDAC2 and 3) as well as class II (HDAC7) are preferentially affected by this treatment. Vorinostat significantlyincreases p21WAF1 expression and apoptosis in MES-SA cells1.Vori

8、nostat inhibits SK-N-SH and SK-N-Be(2)C with the IC25 values of 1 M and 0.5 M, respectively2.Vorinostat is an effective inhibitor of HPV-18 DNA amplification, reduces oncoproteins E6 and E7 activities andtriggers apoptosis in HPV-infected, differentiated cells7.體內(nèi)研究 Vorinostat (50 mg/kg/day) reduces

9、 tumor growth by more than 50% in nude mice injected with 5106 MES-SA cells1.PROTOCOLCell Assay 1 Cell lysates are prepared by using RIPA buffer (25 mM Tris-HCl pH 7.6, 150 mM NaCl, 1% NP-40, 1% sodiumdeoxycholate, 0.1% SDS), and the protein concentration is determined by Bio-Rad DC Protein Assay. P

10、rotein lysatesare separated by SDSand transferred to nitrocellulose membrane. Following antibodies and dilutions are used:rabbit anti HDAC1 (1 g/mL); rabbit anti HDAC2 (1 g/mL); rabbit anti HDAC3 (9 g/mL); rabbit anti HDAC7 (3 g/mL); mouse anti p21WAF1 (0.5 g/mL). As secondary antibodies, the rabbit

11、 anti-mouse and swine anti-rabbit HRP-coupled antibodies at a final concentration of 1 g/mL. An overnight incubation at 4C is used for all primaryantibodies, followed by washing and 2-hours incubation at RT with secondary antibodies. Specific protein bands arevisualized by enhanced chemiluminescence

12、 assay. To demonstrate equal loading of protein samples all western blotsare probed for -tubulin.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Twelve weeks old male mice (n=14) are anesthetized with Isofluran and 5106 MES-SA cells are injectedA

13、dministration 1 subcutaneously into the right flank of the animal. Mice from a control group receives placebo containing 300 L ofempty HOP-CD (2-hydroxypropyl-cyclodextrin) vesicles. Another group of mice receives vorinostat dissolved inHOP-CD at a concentration of 50 mg/kg/day. Both, empty vesicles

14、 and vorinostat are administeredintraperitoneally, starting on the day 4 after the injection of MES-SA tumor cells. Mice body weight and tumor size (wPage 2 of 3 www.MedChemE2 l 0.52; measured by caliper) are estimated twice a week. All mice are treated for 21 days and afterwardssacrificed by cervic

15、al dislocation. Each tumor is isolated as a whole and different tumor parameters are determined.Finally, tumor slices are cryo preserved and formalin fixed (4%) for further analyses.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Mol Psychia

16、try. 2017 May;22(5):711-723. Nat Commun. 2017 Dec 20;8(1):2207. Cell Syst. 2019 Jul 24;9(1):35-48.e5. Stem Cell Reports. 2017 Dec 12;9(6):1948-1960. Biochem Pharmacol. 2019 Jun;164:237-251.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Hrzenjak A et al. Histone deac

17、etylase inhibitor vorinostat suppresses the growth of uterine sarcomas in vitro and in vivo. Mol Cancer. 2010 Mar 4;9:49.2. Lautz TB, et al. The effect of vorinostat on the development of resistance to Doxorubicin in neuroblastoma.PLoS One. 2012;7(7):e40816.3. Richon VM, et al. A class of hybrid pol

18、ar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci U S A. 1998 Mar17;95(6):3003-7.4. Xu WS, et al. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene. 2007 Aug 13;26(37):5541-52.5. Prez-Caams A, et al. Sphingomyelin-induced inhibition of the plasma membrane calcium ATPase causes neurodegeneration in type A Niemann