Droxinostat

 

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Biological Activity

Description	Droxinostat (CMH, 5809354) is a selective inhibitor of HDAC, mostly for HDACs 6 and 8 with IC50 of 2.47μM and 1.46 μM, greater than 8-fold selective against HDAC3 and no inhibition to HDAC1, 2, 4, 5, 7, 9, and 10.
Targets	HDAC3	HDAC6	HDAC8
IC50	16.9 μM	2.47 μM	1.46 μM [3]
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(Only for 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.

Animal Study: ^[2]

Animal Models	Male severe combined immunodeficient (SCID) mice models treated with PPC-1 cells
Dosages
Administration
Solubility	30% propylene glycol, 5% Tween 80, 65% D5W, 30 mg/mL

1

References

Chemical Information

Download Droxinostat SDF

Chemical Name	4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide

Preparing Stock Solutions

Stock Solution (1ml DMSO)	1mM	10mM	20mM	30mM
Mass(mg)	0.24369	2.4369	4.8738	7.3107

Customer Reviews (1)

Click to enlarge	Rating
	Source	Dr. Zhang of Tianjin Medical University. Droxinostat purchased from Selleck
	Method	Western blot
	Cell Lines	Breast cancer cells line T47D
	Concentrations	0.01-10 μM
	Incubation Time
	Results	Droxinostat treatment resulted in a reduction of Histone H3 acetylation in T47D cells.

Product Citations (1)

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  Acetylation limits 53BP1 association with damaged chromatin to promote homologous recombination. [Tang J, et al. Nat Struct Mol Biol 2013;20(3):317-25]