product name Droxinostat
Description: Droxinostat is a selective inhibitor of HDAC, mostly for HDACs 6 and 8 with IC50 of 2.47 μM and 1.46 μM, it exhibits greater than 8-fold selectivity against HDAC3 and no inhibition to HDAC1, 2, 4, 5, 7, 9, and 10. When tested with prostate cancer line PPC-1 cells, droxinostat treatment selectively inhibited HDAC3, HDAC6, and HDAC8 activity at the concentration of 50 μM/L which sensitized cells to death ligands. In androgen-dependent CaP cells, administration of droxinostat selectively inhibited HDACs and downregulated c-FLP expression which resulted in cells apoptosis.
References: Cancer Res. 2006 Feb 15;66(4):2367-75; Mol Cancer Ther. 2010 Jan;9(1):246-56.
243.69
Formula
C11H14ClNO3
CAS No.
99873-43-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 49 mg/mL (201.1 mM)
Water: <1 mg/mL
Ethanol: 49 mg/mL (201.1 mM)
Solubility (In vivo)
30% propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
Synonyms
NS 41080
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19425666
| In Vitro |
In vitro activity: 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). 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. 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). 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 Kinase Assay: HDAC inhibition is assessed using the CycLex HDACs fluorometric assay according to the manufacturers 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: 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. |
|---|---|
| In Vivo | In SCID mice models, Droxinostat (30 μM)-treated PPC-1 cells results in decreased distant tumor formation than untreated cells. |
| Animal model | |
| Formulation & Dosage | |
| References | Cancer Res. 2006 Feb 15;66(4):2367-75; J Natl Cancer Inst. 2007 May 16;99(10):811-22; Mol Cancer Ther. 2010 Jan;9(1):246-56. |
