Droxinostat | CAS#99873-43-5 | HDAC inhibitor

MedKoo Cat#: 401430 | Name: Droxinostat

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Droxinostat (CAS No. 99873-43-5), also known as NS 41080, is a selective histone deacetylase (HDAC) inhibitor. It exhibits potent inhibitory activity against HDAC6 and HDAC8, with IC₅₀ values of 2.47 μM and 1.46 μM, respectively. It also inhibits HDAC3 with an IC₅₀ of 16.9 μM, while showing minimal to no activity against other HDAC isoforms such as HDAC1, 2, 4, 5, 7, 9, and 10 .

Chemical Structure

Droxinostat

CAS#99873-43-5

Theoretical Analysis

MedKoo Cat#: 401430

Name: Droxinostat

CAS#: 99873-43-5

Chemical Formula: C11H14ClNO3

Exact Mass: 243.0662

Molecular Weight: 243.69

Elemental Analysis: C, 54.22; H, 5.79; Cl, 14.55; N, 5.75; O, 19.70

Price and Availability

Size	Price	Availability
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,850.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Related CAS #

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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

Product Data

Instruction

View handling instruction

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/

	Solvent	mg/mL	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

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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.

1: Alrouji M, Venkatesan K, Alshammari MS, Alhumaydhi FA, Shafi S, Sharaf SE, Shahwan M, Shamsi A. Repurposed drugs as histone deacetylase 8 inhibitors: Implications in cancer and neuropathological conditions. Front Pharmacol. 2024 Nov 14;15:1488585. doi: 10.3389/fphar.2024.1488585. PMID: 39611171; PMCID: PMC11602702. 2: 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. 3: 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. 4: 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. 5: 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. 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: 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. 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: 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.