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JNJ-26481585Potent HDAC inhibitor

JNJ-26481585

Catalog No. A4090
Size Price Stock Qty
10mM (in 1mL DMSO) $132.00 In stock
Evaluation Sample $28.00 In stock
5mg $120.00 In stock
10mg $210.00 In stock
50mg $420.00 In stock
200mg $930.00 In stock

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Sample solution is provided at 25 µL, 10mM.

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Chemical structure

JNJ-26481585

Related Biological Data

JNJ-26481585

Related Biological Data

JNJ-26481585

Biological Activity

Description Quisinostat (JNJ-26481585) is a novel second-generation inhibitor of HDAC with highest potency for HDAC1 with IC50 of 0.11 nM.
Targets HDAC1 HDAC2 HDAC4 HDAC10 HDAC11  
IC50 0.11 nM 0.33 nM 0.64 nM 0.46 nM 0.37 nM  

Protocol

Kinase experiment [1]:

Inhibitory activities

Recombinant HDAC activity assays were done by Reaction Biology Corporation. In all cases, full-length HDAC proteins were expressed using baculovirus-infected Sf9 cells. In addition, HDAC3 was coexpressed as a complex with human NCOR2. For assessing activity of HDAC1-containing cellular complexes, immunoprecipitated HDAC1 complexes were incubated with an [3H]acetyllabeled fragment of histone H4 peptide [biotin-(6-aminohexanoic)Gly-Ala-(acetyl[3H])Lys-Arg-His-Arg-Lys-Val-NH2]. Equal amounts of HDAC1 were immunoprecipitated as indicated by Western blot analysis. HDAC1 activity results are presented as mean ± SD of three independent experiments on a single lysate.

Cell experiment [1]:

Cell lines

Non-small cell lung carcinoma (NSCLC) cell lines; hematologic cell lines; human tumor cells; human A2780 ovarian carcinoma cells.

Preparation method

Soluble in DMSO > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

cell proliferation: 72 h, apoptosis assays: 24, 48, and 96 h.

Applications

In all lung, breast, colon, prostate, brain, and ovarian tumor cell lines tested, JNJ-26481585 inhibits cell proliferation with IC50 values of 3.1-246 nM. In A2780 ovarian tumor cells, JNJ-26481585 (3-300 nM) significantly and dose-dependently increases the amount of cells positive for Annexin V, which indicates apoptosis.

Animal experiment [1]:

Animal models

Male athymic nu/nu CD-1 mice injected s.c. with human A2780-p21waf1,cip1 ZsGreen ovarian tumors cells

Dosage form

10 mg/kg i.p. and 40 mg/kg p.o.; once daily for 3 d.

Preparation method

Formulated at 2 mg/mL in 20% hydroxypropyl-β-cyclodextrin (final pH 8.7).

Applications

In the HDAC1-responsive A2780 ovarian tumor screening model, JNJ-26481585 induces a bright and intense fluorescence, which is not uniformly distributed throughout the tissue and fully predicts tumor growth inhibition. Also, JNJ-26481585 induces potent H3 acetylation in the tumor tissue. In HCT116 colon xenografts, JNJ-26481585 (once daily, 10 mg/kg i.p.) for 14 days inhibits tumor volume by 76% and induces H3 acetylation.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Arts J, King P, Marin A, et al. JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res, 2009, 15(22): 6841-6851.

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Chemical Properties

Cas No. 875320-29-9 SDF Download SDF
Synonyms JNJ26481585
Chemical Name N-hydroxy-2-[4-[[(1-methylindol-3-yl)methylamino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide
Canonical SMILES CN1C=C(C2=CC=CC=C21)CNCC3CCN(CC3)C4=NC=C(C=N4)C(=O)NO
Formula C21H26N6O2 M.Wt 394.48
Solubility Soluble in DMSO > 10 mM Storage Store at -20°C
General tips No
Shipping Condition No

View Related Products By Research Topics

Research Update

1. Initial testing (stage 1) of the histone deacetylase inhibitor, quisinostat (JNJ-26481585), by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 2014 Feb;61(2):245-52. doi: 10.1002/pbc.24724. Epub 2013 Sep 4.
Abstract
JNJ-26481585, a selective inhibitor of Class I and II HDACs, exhibited prolonged pharmacodynamic effects in vivo and displayed higher antitumoral efficacy as a signle agent.
2. Severe SMA mice show organ impairment that cannot be rescued by therapy with the HDACi JNJ-26481585. Eur J Hum Genet. 2013 Jun;21(6):643-52. doi: 10.1038/ejhg.2012.222. Epub 2012 Oct 17.
Abstract
JNJ-26481585, a pan-HDACi, up-regulated SMN levels in SMA fibroblast cell lines but failed to prolong survival in SMA mice despite mild improvements in motor abilities and weight progression.
4. Preclinical anti-myeloma activity of the novel HDAC-inhibitor JNJ-26481585. Br J Haematol. 2010 May;149(4):529-36. doi: 10.1111/j.1365-2141.2010.08126.x. Epub 2010 Mar 13.
Abstract
The treatment of JNJ-26481585 resulted in histone acetylation, a shift in Bcl2-family members towards proapoptotic bias, attenuation of growth and survival pathway activity and Hsp72 induction in both human MM cells and primary MM samples, where Mcl-1 depletion and Hsp72 induction were two reliable features observed in primary MM samples. JNJ-26481585 alone or in combination with anti-myeloma therapeutic agents induced myeloma cell death.
5. Preclinical antileukemia activity of JNJ-26481585, a potent second-generation histone deacetylase inhibitor. Leuk Res. 2010 Feb;34(2):221-8. doi: 10.1016/j.leukres.2009.07.024. Epub 2009 Aug 13.
Abstract
JNJ-26481585 alone or in combination with decitabine exhibits anti-leukemia activity in leukemia cell lines and primary human leukemia cells.

Background

JNJ-26481585 is a novel histone deacetylase (HDAC) inhibitor that exerts a strong potency towards class I HDAC (including HDAC1, HDAC2 and HDAC3), with values of inhibition constant IC50 of 0.11, 0.33 and 4.8 nmol/L respectively, leading to strong anti-proliferative activities (IC50 ranging from 3.1 to 246 nmol/L) against a broad range of cancer cell lines including lung, breast, colon, prostate, brain and overian cancer cell lines. Recent study results have shown that JNJ-26481585 strongly induce the HDAC1-suppressed p21waf1,cip1 promoter in vivo, histone H3 acetylation in tumor tissue and apoptosis in human colon cancer cell lines (both APC wild-type and mutant) in vitro.

Reference

Arts J, King P, Mariën A, Floren W, Beliën A, Janssen L, Pilatte I, Roux B, Decrane L, Gilissen R, Hickson I, Vreys V, Cox E, Bol K, Talloen W, Goris I, Andries L, Du Jardin M, Janicot M, Page M, van Emelen K, Angibaud P. JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res. 2009;15(22):6841-6851