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Synonyms | NS 41080 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C11H14ClNO3 |
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分子量 | 243.69 | CAS No. | 99873-43-5 | ||||
Solubility (25°C)* | 体外 | DMSO | 49 mg/mL (201.07 mM) | ||||
Ethanol | 49 mg/mL (201.07 mM) | ||||||
Water | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | Droxinostat (NS 41080) is a selective inhibitor of HDAC, mostly for HDACs 6 and 8 with IC50 of 2.47 μM and 1.46 μM, greater than 8-fold selective against HDAC3 and no inhibition to HDAC1, 2, 4, 5, 7, 9, and 10. |
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in vitro | Droxinostat is originally identified as a sensitizer of PPC-1 cells to FAS and TRAIL by downregulating the expression of c-Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein (c-FLIP). [1] In PPC-1 cells cultured in suspension but not adherent conditions, Droxinostat (20 μM–60 μM) sensitizes cells to anoikis by initially activating caspase 8 with subsequent activation of the mitochondrial pathway. Similarly, Droxinostat also sensitizes other cancer cell lines including PC-3, DU-145, T47D, and OVCAR-3, but not LNCaP or MB-MDA-468, to anoikis or CH-11-induced apoptosis. [2] However, the direct targets of Droxinostat remains enigma until recently. It is revealed that in histone deacetylases (HDAC) isoform 1-10, Droxinostat selective inhibits HDAC3, 6, and 8, with IC50 values of 16.9 μM, 2.47 μM, and 1.46 μM, respectively, without inhibiting other HDAC members (IC50 > 20 μM). [3] In MCF-7 breast cancer cells, Droxinostat (10 μM–100 μM) sensitizes cells to apoptosis by decreasing c-FLIPL and c-FLIPS expression, reducing cell survival, and inducing apoptosis. [4] |
in vivo | In SCID mice models, Droxinostat (30 μM)-treated PPC-1 cells results in decreased distant tumor formation than untreated cells. [2] |
特徴 | Selective inhibitor of HDAC3, HDAC6,and HDAC8. |
キナーゼアッセイ | HDAC Inhibition Assay | |
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HDAC inhibition is assessed using the CycLex HDACs fluorometric assay according to the manufacturer's protocol and using crude nuclear extract from HeLa cells (principally HDAC1 and HDAC2). The relative activity is expressed as (fluorescence intensity of treated samples/fluorescence intensity of controls) × 100 | ||
細胞アッセイ | 細胞株 | PPC-1 cells |
濃度 | 0–100 μM, dissolved in DMSO (final concentration of DMSO is 0.5%) | |
反応時間 | 24 hours | |
実験の流れ | PPC-1 cells (1 × 104) are seeded overnight into 96-well flat-bottomed plates in 100 μL of medium containing 2.5% FCS. The next day, Droxinostat is added. CH-11 antibody (100 ng/mL) is then added and the cells are incubated for 24 hours before assessing cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye reduction assay. | |
動物実験 | 動物モデル | Male severe combined immunodeficient (SCID) mice models treated with PPC-1 cells |
投薬量 | ||
投与方法 |
Data from [Data independently produced by PLoS One, 2014, 9(8), e102684]
, , Dr. Zhang of Tianjin Medical University
Effects of histone H4 hyperacetylation on inhibiting MMP2 and MMP9 in human amniotic epithelial cells and in premature rupture of fetal membranes [ Exp Ther Med, 2021, 21(5):515] | PubMed: 33815588 |
Glycogen synthase kinase-3 inhibition overcomes epithelial-mesenchymal transition-associated resistance to osimertinib in EGFR-mutant lung cancer [ Cancer Sci, 2020, 111(7):2374-2384] | PubMed: 32391602 |
Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer [ Cancer Res, 2018, 78(20):5731-5740] | PubMed: 30135193 |
Histone Deacetylase 3 Inhibition Overcomes BIM Deletion Polymorphism–Mediated Osimertinib Resistance in EGFR-Mutant Lung Cancer [Tanimoto A Clin Cancer Res, 2017, 23(12):3139-3149] | PubMed: 27986747 |
Identification of a cancer stem cell-specific function for the histone deacetylases, HDAC1 and HDAC7, in breast and ovarian cancer. [ Oncogene, 2017, 36(12):1707-1720] | PubMed: 27694895 |
Inhibition of class I histone deacetylases by romidepsin potently induces Epstein-Barr virus lytic cycle and mediates enhanced cell death with ganciclovir [Hui KF, et al. Int J Cancer, 2016, 138(1):125-36] | PubMed: 26205347 |
Droxinostat, a Histone Deacetylase Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cell Lines via Activation of the Mitochondrial Pathway and Downregulation of FLIP. [ Transl Oncol, 2016, 9(1):70-78] | PubMed: 26947884 |
AF4 and AF4-MLL mediate transcriptional elongation of 5-lipoxygenase mRNA by 1, 25-dihydroxyvitamin D3 [ Oncotarget, 2015, 6(28):25784-800] | PubMed: 26329759 |
PU.1 Suppresses Th2 Cytokine Expression via Silencing of GATA3 Transcription in Dendritic Cells [ PLoS One, 2015, 10(9):e0137699] | PubMed: 26361334 |
Evaluation of histone deacetylase inhibitors (HDACi) as therapeutic leads for human African trypanosomiasis (HAT). [Carrillo AK, et al. Bioorg Med Chem, 2015, 10.1016/j.bmc.2014.12.066] | PubMed: 25637120 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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