Droxinostat

Catalog No.S1422 Batch:S142201

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Technical Data

Formula

C11H14ClNO3
Molecular Weight 243.69 CAS No. 99873-43-5
Solubility (25°C)* In vitro DMSO 49 mg/mL (201.07 mM)
Ethanol 49 mg/mL (201.07 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
30%propylene glycol 5%Tween80 65%D5W
30.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description 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.
Targets
HDAC8 [3] HDAC6 [3] HDAC3 [3] HDAC9 [3] HDAC10 [3] View More
1.46 μM 2.47 μM 16.9 μM >20 μM >20 μM
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]
Features Selective inhibitor of HDAC3, HDAC6,and HDAC8.

Protocol (from reference)

Kinase Assay:[3]
  • HDAC Inhibition Assay

    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
Cell Assay:[1]
  • Cell lines

    PPC-1 cells

  • Concentrations

    0–100 μM, dissolved in DMSO (final concentration of DMSO is 0.5%)

  • Incubation Time

    24 hours

  • Method

    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.

Customer Product Validation

Data from [Data independently produced by PLoS One, 2014, 9(8), e102684]

, , Dr. Zhang of Tianjin Medical University

Selleck's Droxinostat has been cited by 13 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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