Vorinostat-SAHA-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEVorinostatCat. No.: HY-10221CAS No.: 149647-78-9Synonyms: SAHA分式: CHNO分量: 264.32作靶點(diǎn): HDAC; Autophagy; Mitophagy作通路: Cell Cycle/DNA Damage; Epigenetics; Autophagy儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 mo

2、nth溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (378.33 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)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(qǐng)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(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙?/p>

3、案，配制前請(qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)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 solution2. 請(qǐng)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 soluti

4、on1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (9.46 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Vorinostat種有效的，可服的 HDAC1，HDAC2，HDAC3 (Class I)，HDAC7 (Class II) 和 Class IV(HDAC11) 的抑制劑，對(duì) HDAC1/3 的 ID50 值分別為 10 nM 和 20 nM。IC50 & Target HDAC1

5、HDAC3 HDAC2 HDAC710 nM (ID50) 20 nM (ID50)HDAC11 Mitophagy Autophagy體外研究 Vorinostat efficiently suppresses MES-SA cell growth at a low dosage (3 M) already after 24 hourstreatment. HDACs class I (HDAC2 and 3) as well as class II (HDAC7) are preferentially affected by thistreatment. Vorinostat signif

6、icantly increases p21WAF1 expression and apoptosis in MES-SA cells 1.Vorinostat inhibits SK-N-SH and SK-N-Be(2)C with the IC25 values of 1 M and 0.5 M, respectively 2.體內(nèi)研究 Vorinostat (50 mg/kg/day) reduces tumor growth by more than 50% in nude mice injected with 5106 MES-SA cells 1.PROTOCOLCell Assa

7、y 1 Cell lysates are prepared by using RIPA buffer (25 mM Tris-HCl pH 7.6, 150 mM NaCl, 1% NP-40, 1%sodium deoxycholate, 0.1% SDS), and the protein concentration is determined by Bio-Rad DC ProteinAssay. Protein lysates are separated by SDSand transferred to nitrocellulose membrane. Followingantibod

8、ies and dilutions are used: rabbit anti HDAC1 (1 g/mL); rabbit anti HDAC2 (1 g/mL); rabbit antiHDAC3 (9 g/mL); rabbit anti HDAC7 (3 g/mL); mouse anti p21WAF1 (0.5 g/mL). As secondaryantibodies, the rabbit anti-mouse and swine anti-rabbit HRP-coupled antibodies at a final concentration of 1 g/mL. An

9、overnight incubation at 4C is used for all primary antibodies, followed by washing and 2-hoursincubation at RT with secondary antibodies. Specific protein bands are visualized by enhancedchemiluminescence assay. To demonstrate equal loading of protein samples all western blots are probed for-tubulin

10、.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 injectedAdministration 1 subcutaneously into the right flank of the animal. Mice from a control group rec

11、eives placebo containing 300L of empty HOP-CD (2-hydroxypropyl-cyclodextrin) vesicles. Another group of mice receives vorinostatdissolved in HOP-CD at a concentration of 50 mg/kg/day. Both, empty vesicles and vorinostat areadministered intraperitoneally, starting on the day 4 after the injection of

12、MES-SA tumor cells. Mice bodyweight and tumor size (w2 l 0.52; measured by caliper) are estimated twice a week. All mice are treatedfor 21 days and afterwards sacrificed by cervical dislocation. Each tumor is isolated as a whole and different2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEtumor par

13、ameters are determined. Finally, tumor slices are cryo preserved and formalin fixed (4%) for furtheranalyses.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 Psychiatry. 2017 May;22(5):711-723. Nat Commun. 2017 Dec 20;8(1):2207. Cell Syst

14、. 2019 Jul 5. pii: S2405-4712(19)30200-5. Stem Cell Reports. 2017 Dec 12;9(6):1948-1960. Biochem Pharmacol. 2019 Jun;164:237-251.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Hrzenjak A et al. Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas

15、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 polar inducers of transformed cell differentiation inhibits histone deacetyl

16、ases. Proc Natl Acad Sci US A. 1998 Mar 17;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 typeA Niemann-Pick disease. Mol Psychiatry. 2017 May;22(5):711-723.6. Wang J, et al. Snail determines the therapeutic response to mTOR kinase inhibitors by transcriptional repres