Panobinostat-LBH589-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPanobinostatCat. No.: HY-10224CAS No.: 404950-80-7Synonyms: LBH589; NVP-LBH589分式: CHNO分量: 349.43作靶點(diǎn): HDAC; Autophagy作通路: Cell Cycle/DNA Damage; Epigenetics; Autophagy儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C

2、 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 57 mg/mL (163.12 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.8618 mL 14.3090 mL 28.6180 mL5 mM 0.5724 mL 2.8618 mL 5.7236 mL10 mM 0.2862 mL 1.4309 mL 2.8618 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

3、當(dāng)?shù)娜芙獍?，配制前?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 (7.15 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 (7.15 mM); Clear so

4、lution1/3 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 (7.15 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Panobinostat種選擇性組蛋去?；?(HDAC) 抑制劑。IC50 & Target HDAC體外研究 Panobinosta (LBH589) induces apoptosis of both MOLT-4 and Reh cells in a time- and

5、dose-dependentmanner. Panobinosta treatment results in histone (H3K9 and H4K8) hyperacetylation and regulation of cell-cycle control genes in Reh cells 1. Panobinostat exhibites potent antiproliferative activity in human NSCLCcell lines with the IC50 ranging from 5 to 100 nM 2.體內(nèi)研究 Panobinosta (10,

6、20 mg/kg, i.p.) significantly slows tumor growth derived from Meso and NSCLC cells in vivomodels. Panobinosta markedly increases acetylation of histone H3 and H4 of H69 human SCLC cells harvestfrom SCID mice 2. Panobinostat (5, 10 and 20 mg/kg i.p.) demonstrates a clear benefit of decreased tumorbur

7、den, significantly improves TTE and reduces bone density loss in a disseminated multiple myelomamouse model 3.PROTOCOLCell Assay 1 Cells are washed with ice-cold PBS containing 0.1 mM sodium orthovanadate, and total proteins are isolatedusing RIPA lysis buffer, which includes protease inhibitors (le

8、upeptin, antipain, and aprotinin), 0.5 mM PMSF,and 0.2 mM sodium orthovanadate. Protein amounts are quantified using the Bio-Rad protein assay. Equalamounts of proteins are loaded onto an sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel, transferred onto nitrocellulose membra

9、ne, and probed with the antibody of interest: mousemonoclonal c-Myc and mouse monoclonal p21 antibodies; rabbit polyclonal phospho-Histone H2A.X, rabbitpolyclonal acetyl-Histone H3 (Lys9), and rabbit polyclonal acetyl-Histone H4 (Lys8) antibodies; mousemonoclonal p27/KIP1 antibody; mouse monoclonal

10、anti-actin; and mouse monoclonal anti-GADD45G.Membranes are then washed, reprobed with appropriate horseradish peroxidase-conjugated secondaryantibodies, and developed with SuperSignal chemiluminescent substrate.MCE has not independently confirmed the accuracy of these methods. They are for referenc

11、e only.Animal AE17 and TC-1 cancer cells (1106 cells) are injected into the flanks of adult female C57Bl/6 mice andAdministration 1 severe combined immunodeficiency (SCID) mice. M30 (10106 cells), A549 (5106 cells), H69 (2.5106cells), BK-T (6.5106), H526 (10106), and RG1 (10106) cells are also injec

12、ted, but in the presence ofmatrigel, into the flanks of SCID mice. When tumors reach 100 to 500 mm3, panobinostat is administered viai.p. injections (10-20 mg/kg) on a daily schedule (5-days-on, 2-days-off regimen) for the entire duration of theexperiment. Control micereceive i.p. injections with de

13、xtrose 5% in water. Every tumor is measured with acaliper at least twice weekly. For evaluation of the effects of combination therapy on SCLC-derived tumors,SCID mice with H69 tumors are administered panobinostat. Three days after the initiation of panobinostat,2/3 Master of Small Molecules 您邊的抑制劑師w

14、ww.MedChemEand again 1 wk later, etoposide (40 mg/kg) is administered i.p.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) Cancer Res. 2016 Dec 1;76(23):7001-7011. PLoS Pathog. 2018 Sep 13;14(9):e1007267. Mol Ther Oncolytics. 2019 Feb 5;12:23

15、5-245. Drug Des Devel Ther. 2018 Apr 30;12:1009-1017. Insect Mol Biol. 2019 Aug 7.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Scuto A, et al. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis inPh- acute lymphobla

16、stic leukemia cells. Blood. 2008 May 15;111(10):5093-100.2. Crisanti MC, et al. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo withparticular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31.3. Ocio EM, et al. In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with eitherbortezomib or lenalidomide in multiple