Quisinostat HCl

featured

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

Description:Quisinostat, also known as JNJ-26481585, is an orally bioavailable, second-generation, hydroxamic acid-based inhibitor of histone deacetylase (HDAC) with potential antineoplastic activity. HDAC inhibitor JNJ-26481585 inhibits HDAC leading to an accumulation of highly acetylated histones, which may result in an induction of chromatin remodeling; inhibition of the transcription of tumor suppressor genes; inhibition of tumor cell division; and the induction of tumor cell apoptosis. HDAC, an enzyme upregulated in many tumor types, deacetylates chromatin histone proteins. Compared to some first generation HDAC inhibitors, JNJ-26481585 may induce superior HSP70 upregulation and bcl-2 downregulation.

Price and Availability

Quisinostat hydrochloride, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 201612Name: Quisinostat HClCAS#: 1083078-98-1 (HCl)Chemical Formula: C21H27ClN6O2 Exact Mass: 394.21172Molecular Weight: 430.937Elemental Analysis: C, 58.53; H, 6.32; Cl, 8.23; N, 19.50; O, 7.43

Related CAS #:1083078-98-1 (HCl)875320-29-9 (free base)875320-31-3 (2HCl)

Synonym:JNJ26481585; JNJ-26481585; JNJ 26481585; JNJ-26481585-AAC; Quisinostat HCl; Quisinostat hydrochloride.

IUPAC/Chemical Name:N-hydroxy-2-(4-((((1-methyl-1H-indol-3-yl)methyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxamide hydrochloride

InChi Key:TWNOICNTTFKOHQ-UHFFFAOYSA-N

InChi Code:InChI=1S/C21H26N6O2.ClH/c1-26-14-17(18-4-2-3-5-19(18)26)11-22-10-15-6-8-27(9-7-15)21-23-12-16(13-24-21)20(28)25-29;/h2-5,12-15,22,29H,6-11H2,1H3,(H,25,28);1H

SMILES Code:O=C(C1=CN=C(N2CCC(CNCC3=CN(C)C4=C3C=CC=C4)CC2)N=C1)NO.[H]Cl

Technical Data

Additional Information

Related CAS#875320-29-9 (Quisinostat free base)1083078-98-1 (Quisinostat hydrochloride) 

References

1: Capasso KE, Manners MT, Quershi RA, Tian Y, Gao R,Hu H, Barrett JE, Sacan A, Ajit SK. Effect of Histone DeacetylaseInhibitor JNJ-26481585 in Pain. J Mol Neurosci. 2014 Aug 2. [Epub aheadof print] PubMed PMID: 25085711.

2: Maes K, De Smedt E, Lemaire M, De Raeve H, Menu E, Van ValckenborghE, McClue S, Vanderkerken K, De Bruyne E. The role of DNA damage andrepair in decitabine-mediated apoptosis in multiple myeloma. Oncotarget.2014 May 30;5(10):3115-29. PubMed PMID: 24833108; PubMed Central PMCID:PMC4102796.

3: Carol H, Gorlick R, Kolb EA, Morton CL, Manesh DM, Keir ST, ReynoldsCP, Kang MH, Maris JM, Wozniak A, Hickson I, Lyalin D, Kurmasheva RT,Houghton PJ, Smith MA, Lock R. Initial testing (stage 1) of the histonedeacetylase inhibitor, quisinostat (JNJ-26481585), by the PediatricPreclinical Testing Program. Pediatr Blood Cancer. 2014Feb;61(2):245-52. doi: 10.1002/pbc.24724. Epub 2013 Sep 4. PubMed PMID:24038993.

4: Venugopal B, Baird R, Kristeleit RS, Plummer R, Cowan R, Stewart A,Fourneau N, Hellemans P, Elsayed Y, McClue S, Smit JW, Forslund A,Phelps C, Camm J, Evans TR, de Bono JS, Banerji U. A phase I study ofquisinostat (JNJ-26481585), an oral hydroxamate histone deacetylaseinhibitor with evidence of target modulation and antitumor activity, inpatients with advanced solid tumors. Clin Cancer Res. 2013 Aug1;19(15):4262-72. doi: 10.1158/1078-0432.CCR-13-0312. Epub 2013 Jun 5.PubMed PMID: 23741066.

5: Schreml J, Riessland M, Paterno M, Garbes L, Roßbach K, Ackermann B,Krämer J, Somers E, Parson SH, Heller R, Berkessel A, Sterner-Kock A,Wirth B. Severe SMA mice show organ impairment that cannot be rescued bytherapy with the HDACi JNJ-26481585. Eur J Hum Genet. 2013Jun;21(6):643-52. doi: 10.1038/ejhg.2012.222. Epub 2012 Oct 17. PubMedPMID: 23073311; PubMed Central PMCID: PMC3658191.

6: Stühmer T, Arts J, Chatterjee M, Borawski J, Wolff A, King P, EinseleH, Leo E, Bargou RC. Preclinical anti-myeloma activity of the novelHDAC-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. PubMed PMID:20331455.

7: 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, TalloenW, Goris I, Andries L, Du Jardin M, Janicot M, Page M, van Emelen K,Angibaud P. JNJ-26481585, a novel "second-generation" oral histonedeacetylase inhibitor, shows broad-spectrum preclinical antitumoralactivity. Clin Cancer Res. 2009 Nov 15;15(22):6841-51. doi:10.1158/1078-0432.CCR-09-0547. Epub 2009 Oct 27. PubMed PMID: 19861438.

8: Tong WG, Wei Y, Stevenson W, Kuang SQ, Fang Z, Zhang M, Arts J,Garcia-Manero G. Preclinical antileukemia activity of JNJ-26481585, apotent second-generation histone deacetylase inhibitor. Leuk Res. 2010Feb;34(2):221-8. doi: 10.1016/j.leukres.2009.07.024. Epub 2009 Aug 13.PubMed PMID: 19682743.

9: Deleu S, Lemaire M, Arts J, Menu E, Van Valckenborgh E, Vande BroekI, De Raeve H, Coulton L, Van Camp B, Croucher P, Vanderkerken K.Bortezomib alone or in combination with the histone deacetylaseinhibitor JNJ-26481585: effect on myeloma bone disease in the 5T2MMmurine model of myeloma. Cancer Res. 2009 Jul 1;69(13):5307-11. doi:10.1158/0008-5472.CAN-08-4472. Epub 2009 Jun 16. PubMed PMID: 19531653.

10: Deleu S, Lemaire M, Arts J, Menu E, Van Valckenborgh E, King P,Vande Broek I, De Raeve H, Van Camp B, Croucher P, Vanderkerken K. Theeffects of JNJ-26481585, a novel hydroxamate-based histone deacetylaseinhibitor, on the development of multiple myeloma in the 5T2MM and5T33MM murine models. Leukemia. 2009 Oct;23(10):1894-903. doi:10.1038/leu.2009.121. Epub 2009 Jun 4. PubMed PMID: 19494837.

11: Dedes KJ, Dedes I, Imesch P, von Bueren AO, Fink D, Fedier A.Acquired vorinostat resistance shows partial cross-resistance to"second-generation" HDAC inhibitors and correlates with loss of histoneacetylation and apoptosis but not with altered HDAC and HAT activities.Anticancer Drugs. 2009 Jun;20(5):321-33. doi:10.1097/CAD.0b013e3283262a32. PubMed PMID: 19322073.

(last updated: 4/20/2016).