Tubacin-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETubacinCat. No.: HY-13428CAS No.: 537049-40-4分式: CHNOS分量: 721.86作靶點(diǎn): HDAC作通路: Cell Cycle/DNA Damage; Epigenetics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(shí)驗(yàn) DMSO : 100 mg/mL (138.53 mM)H2O : 40

2、% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.46 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.46 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Tubacin種有效的，選擇性的 HDAC6 抑制劑，IC50 值為 4 nM，約對 HDAC1 的 350 倍。IC50 & Targ

3、et HDAC6 HDAC3 HDAC8 HDAC14 nM (IC50) 1.27 M (IC50) 1.27 M (IC50) 1.40 M (IC50)HDAC5 HDAC10 HDAC11 HDAC93.35 M (IC50) 3.71 M (IC50) 3.79 M (IC50) 4.31 M (IC50)HDAC2 HDAC7 HDAC46.27 M (IC50) 9.70 M (IC50) 17.30 M (IC50)體外研究 Tubacin preferentially induces -tubulin hyperacetylation at a concentration o

4、f 2.5 M, and induces -tubulinacetylation at 5 M and protects prostate cancer (LNCaP) cells from hydrogen peroxide-induced death at 8M via peroxiredoxin acetylation 1. Tubacin (2.5 and 5 M) specifically induces acetylation of -tubulin inMM cells. Tubacin significantly inhibits both drug-sensitive and

5、 drug-resistant MM cell growth, with IC50 5-20M at 72 h. Tubacin also induces apoptosis by activation of caspases. Moreover, Tubacin inhibits binding ofHDAC6 with dynein, and it induces significant accumulation of polyubiquitinated proteins, when combinedwith bortezomib. Tubacin and bortezomib induc

6、e synergistic antitumor activity in MM cell lines, and inhibitsparacrine MM Cell Growth. Tubacin (5 M) synergistically enhances bortezomib-induced cytotoxicity inpatient MM cells without cytotoxicity to PBMCs 2. Tubacin can concentration-dependently inhibits JEV-induced cytopathic effect and apoptos

7、is, as well as reduces virus yield in human cerebellar medulloblastomacells. The IC50 of virus yield is 0.26 M for Tubacin. Tubacin also meaningfully blocks the production ofintracellular infectious virus particles, with an IC50 of 1.52 M. Tubacin induces the hyperacetylation of aHDAC6 substrate Hsp

8、90 and reduces the interaction of Hsp90 with JEV NS5 protein 3.PROTOCOLCell Assay 3 HDAC inhibitors TSA, VPA, tubacin, and TBSA are used in the assay. Cytotoxicity of HDACi to TE671 andBHK-21 cells is evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. 5 104 cells

9、per well are seeded in 96-well plates and then treated with the indicated concentration of eachHDACi. After 48-h of treatment, 25 L of MTT solution (5 mg/mL) is added to each well and incubated at 37C with 5% CO2 for 3 h. After three washings with phosphate buffer saline (PBS), 100 L DMSO is addedin

10、to each well for dissolving formazan crystals. OD570630 is measured by micro-ELISA reader and survivalrate are calculated to indicate suppressive effects of each HDACi on the survival of TE671 and BHK-21 cells.Survival rate (%) = (Acontrol Aexperiment)/Acontrol) 100%. 50% cytotoxic concentration (CC

11、50) valuesare calculated by computer program 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE J Pharmacol Exp Ther. 2019 Jul 15. pii: jpet.119.258129. Biochemistry and Molecular Biology. Florida Souther

12、n College. 2019 May.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Butler KV, et al. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc.2010 Aug 11;132(31):10842-6.2. Hideshima T, et al. Small-molecule inhibition

13、 of proteasome and aggresome function induces synergistic antitumor activity in multiplemyeloma. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8567-72. Epub 2005 Jun 3.3. Lu CY, et al. Tubacin, an HDAC6 Selective Inhibitor, Reduces the Replication of the Japanese Encephalitis Virus via the Decrease ofViral RNA Synthesis. Int J Mol Sci. 2017 May 1;18(5).MceP