Droxinostat
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MedKoo CAT#: 401430

CAS#: 99873-43-5

Description: Droxinostat, also known as NS 41080, is a selective inhibitor of HDAC3, HDAC6, and HDAC8. Droxinostat shows comparable inhibition of HDAC6 and HDAC8 (IC50 = 2.47 and 1.46 μmol/L, respectively).


Chemical Structure

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Droxinostat
CAS# 99873-43-5

Theoretical Analysis

MedKoo Cat#: 401430
Name: Droxinostat
CAS#: 99873-43-5
Chemical Formula: C11H14ClNO3
Exact Mass: 243.07
Molecular Weight: 243.687
Elemental Analysis: C, 54.22; H, 5.79; Cl, 14.55; N, 5.75; O, 19.70

Price and Availability

Size Price Availability Quantity
25mg USD 250 2 Weeks
50mg USD 450 2 Weeks
100mg USD 750 2 Weeks
200mg USD 1250 2 Weeks
500mg USD 2650 2 Weeks
1g USD 3850 2 Weeks
2g USD 6450 2 Weeks
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Synonym: NS 41080; NS41080; NS-41080; Droxinostat;

IUPAC/Chemical Name: 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide

InChi Key: JHSXDAWGLCZYSM-UHFFFAOYSA-N

InChi Code: InChI=1S/C11H14ClNO3/c1-8-7-9(12)4-5-10(8)16-6-2-3-11(14)13-15/h4-5,7,15H,2-3,6H2,1H3,(H,13,14)

SMILES Code: O=C(NO)CCCOC1=CC=C(Cl)C=C1C

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Droxinostat has shown a potent action against HDAC3, HDAC6, and HDAC8 which are pyrimidyl-hydroxamic acid-dependent histone deacetylases. Chemically Droxinostat stands for 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide. It contains a hydroxamic acid moiety. Caspase 8 is an effective stimulator of apoptosis and its action is inhibited by the protein FLIP. Hence FLIP inhibits apoptosis and Droxinostat targets FLIP induced inhibition of apoptosis.   Droxinostat shows a significant action on gene transcription hence controlling tumor progression. The cells resistant to the caspase mediated apoptotic pathway get sensitized by Droxinostat, hence proving an active agent of introducing death in cancerous cells. (source: http://www.hdacblog.com/2011/10/droxinostat-active-inhibitor-of-hdac3.html).   Current developer:       

Product Data:
Biological target: Droxinostat (NS 41080) is a histone deacetylase (HDAC) inhibitor.
In vitro activity: Droxinostat inhibited proliferation and colony formation of the HCC cell lines examined. Droxinostat suppresses HDAC3 expression and induces histone acetylation and HCC cell death through activation of the mitochondrial apoptotic pathway and downregulation of FLIP, supporting its potential application in the treatment of HCC. Reference: Transl Oncol. 2016 Feb;9(1):70-78. https://pubmed.ncbi.nlm.nih.gov/26947884/
In vivo activity: A semi-quantitative index (SMI) shows that CMH (droxinostat) attenuated lung fibrosis in mice from an index of SMI equals 2 to only 1.1 (Figure 4E), and collagen in Sircoll assay decreased from 200 µg to only 50 µg per lobe (Figure 4F). Thus, CMH shows inhibition of Ku70-deacetylation that may stabilize FLIP and Ku70/FLIP complex in lung myofibroblasts promoting fibrosis, which can be associated to inhibition of SIRT1. Reference: Biomolecules. 2020 Jul 2;10(7):997. https://pubmed.ncbi.nlm.nih.gov/32630842/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 30.0 123.11
DMSO 76.3 313.24
Ethanol 39.5 162.09
Ethanol:PBS (pH 7.2) (1:20) 0.1 0.21

Preparing Stock Solutions

The following data is based on the product molecular weight 243.69 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Liu J, Li G, Wang X, Wang L, Zhao R, Wang J, Kong Y, Ding J, Li J, Zhang L. 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 Feb;9(1):70-78. doi: 10.1016/j.tranon.2016.01.004. PMID: 26947884; PMCID: PMC4800063. 2. Wood TE, Dalili S, Simpson CD, Sukhai MA, Hurren R, Anyiwe K, Mao X, Suarez Saiz F, Gronda M, Eberhard Y, MacLean N, Ketela T, Reed JC, Moffat J, Minden MD, Batey RA, Schimmer AD. Selective inhibition of histone deacetylases sensitizes malignant cells to death receptor ligands. Mol Cancer Ther. 2010 Jan;9(1):246-56. doi: 10.1158/1535-7163.MCT-09-0495. Epub 2010 Jan 6. PMID: 20053768. 3. Konikov-Rozenman J, Breuer R, Kaminski N, Wallach-Dayan SB. CMH-Small Molecule Docks into SIRT1, Elicits Human IPF-Lung Fibroblast Cell Death, Inhibits Ku70-deacetylation, FLIP and Experimental Pulmonary Fibrosis. Biomolecules. 2020 Jul 2;10(7):997. doi: 10.3390/biom10070997. PMID: 32630842; PMCID: PMC7408087.
In vitro protocol: 1. Liu J, Li G, Wang X, Wang L, Zhao R, Wang J, Kong Y, Ding J, Li J, Zhang L. 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 Feb;9(1):70-78. doi: 10.1016/j.tranon.2016.01.004. PMID: 26947884; PMCID: PMC4800063. 2. Wood TE, Dalili S, Simpson CD, Sukhai MA, Hurren R, Anyiwe K, Mao X, Suarez Saiz F, Gronda M, Eberhard Y, MacLean N, Ketela T, Reed JC, Moffat J, Minden MD, Batey RA, Schimmer AD. Selective inhibition of histone deacetylases sensitizes malignant cells to death receptor ligands. Mol Cancer Ther. 2010 Jan;9(1):246-56. doi: 10.1158/1535-7163.MCT-09-0495. Epub 2010 Jan 6. PMID: 20053768.
In vivo protocol: 1. Konikov-Rozenman J, Breuer R, Kaminski N, Wallach-Dayan SB. CMH-Small Molecule Docks into SIRT1, Elicits Human IPF-Lung Fibroblast Cell Death, Inhibits Ku70-deacetylation, FLIP and Experimental Pulmonary Fibrosis. Biomolecules. 2020 Jul 2;10(7):997. doi: 10.3390/biom10070997. PMID: 32630842; PMCID: PMC7408087.

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1: Huang Y, Yang W, Zeng H, Hu C, Zhang Y, Ding N, Fan G, Shao L, Kuang B. Droxinostat sensitizes human colon cancer cells to apoptotic cell death via induction of oxidative stress. Cell Mol Biol Lett. 2018 Jul 28;23:34. doi: 10.1186/s11658-018-0101-5. PMID: 30065760; PMCID: PMC6064062.


2: Liu J, Li G, Wang X, Wang L, Zhao R, Wang J, Kong Y, Ding J, Li J, Zhang L. 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 Feb;9(1):70-78. doi: 10.1016/j.tranon.2016.01.004. PMID: 26947884; PMCID: PMC4800063.


3: Wood TE, Dalili S, Simpson CD, Sukhai MA, Hurren R, Anyiwe K, Mao X, Suarez Saiz F, Gronda M, Eberhard Y, MacLean N, Ketela T, Reed JC, Moffat J, Minden MD, Batey RA, Schimmer AD. Selective inhibition of histone deacetylases sensitizes malignant cells to death receptor ligands. Mol Cancer Ther. 2010 Jan;9(1):246-56. doi: 10.1158/1535-7163.MCT-09-0495. Epub 2010 Jan 6. PMID: 20053768.


4: Yao S, Deng M, Du X, Huang R, Chen Q. A Novel Hypoxia Related Marker in Blood Link to Aid Diagnosis and Therapy in Osteoarthritis. Genes (Basel). 2022 Aug 23;13(9):1501. doi: 10.3390/genes13091501. PMID: 36140669; PMCID: PMC9498462.


5: Song Z, Yang L, Hu W, Yi J, Feng F, Zhu L. 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 May;21(5):515. doi: 10.3892/etm.2021.9946. Epub 2021 Mar 22. PMID: 33815588; PMCID: PMC8014974.


6: Huang HJ, Huang HY, Hsieh-Li HM. MGCD0103, a selective histone deacetylase inhibitor, coameliorates oligomeric Aβ25-35 -induced anxiety and cognitive deficits in a mouse model. CNS Neurosci Ther. 2019 Feb;25(2):175-186. doi: 10.1111/cns.13029. Epub 2018 Jul 5. PMID: 29978554; PMCID: PMC6488906.


7: Welker Leng KR, Castañeda CA, Decroos C, Islam B, Haider SM, Christianson DW, Fierke CA. Phosphorylation of Histone Deacetylase 8: Structural and Mechanistic Analysis of the Phosphomimetic S39E Mutant. Biochemistry. 2019 Nov 12;58(45):4480-4493. doi: 10.1021/acs.biochem.9b00653. Epub 2019 Nov 4. PMID: 31633931; PMCID: PMC6903415.


8: McCourt C, Maxwell P, Mazzucchelli R, Montironi R, Scarpelli M, Salto-Tellez M, O'Sullivan JM, Longley DB, Waugh DJ. Elevation of c-FLIP in castrate- resistant prostate cancer antagonizes therapeutic response to androgen receptor- targeted therapy. Clin Cancer Res. 2012 Jul 15;18(14):3822-33. doi: 10.1158/1078-0432.CCR-11-3277. Epub 2012 May 23. PMID: 22623731; PMCID: PMC3512078.


9: Konikov-Rozenman J, Breuer R, Kaminski N, Wallach-Dayan SB. CMH-Small Molecule Docks into SIRT1, Elicits Human IPF-Lung Fibroblast Cell Death, Inhibits Ku70-deacetylation, FLIP and Experimental Pulmonary Fibrosis. Biomolecules. 2020 Jul 2;10(7):997. doi: 10.3390/biom10070997. PMID: 32630842; PMCID: PMC7408087.


10: Bijangi-Vishehsaraei K, Huang S, Safa AR, Saadatzadeh MR, Murphy MP. 4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide (CMH) targets mRNA of the c-FLIP variants and induces apoptosis in MCF-7 human breast cancer cells. Mol Cell Biochem. 2010 Sep;342(1-2):133-142. doi: 10.1007/s11010-010-0477-7. Epub 2010 May 6. PMID: 20446019; PMCID: PMC4450253.


11: Yue W, Wang JP, Zhang L, Wang W, Santen RJ, Aiyar SE. Induction of apoptosis in hormone refractory breast cancer: horizontal modulation is superior to vertical. J Exp Ther Oncol. 2013;10(3):169-79. PMID: 24416991.