Quisinostat HCl

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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).

MedKoo，由化学家和药学家陈清奇博士。北卡罗莱纳州的研究三角区（ResearchTrianglePark,简称RTP)，是一家以研发、生产和销售小分子抗癌化合物为主的医药科技公司，该公司的业务范围主要是为全球所有从事抗癌药物研究和开发的制药公司，高校，研究院所，政府相关机构提供与抗癌药物分子相关的产品、试剂和技术服务。

中文名MedKoo中    文美帝药库医药科技公司创立于2008年总部位于美国东海岸

MedKoo是世界领先的供应商之一的抗癌化学试剂和激酶抑制剂。我们制造、销售和分发高质量的抗癌小分子肿瘤学研究试剂。我们的使命是建立世界上最全面的抗癌小分子的集合。我们也为医药行业提供高质量的研究服务、医学研究机构和学术机构。我们致力于提供优质的服务。

MedKoo是世界领先的供应商之一的抗癌化学试剂和激酶抑制剂。我们制造、销售和分发高质量的抗癌小分子肿瘤学研究试剂。我们的使命是建立世界上最全面的抗癌小分子的集合。我们也为医药行业提供高质量的研究服务、医学研究机构和学术机构。我们致力于提供优质的服务和分子有竞争力的价格。MedKoo是您可靠的合作伙伴采购药物发现和药物分子。

MedKoo是世界的抗癌化学试剂和激酶抑制剂供应商之一。我们制造，销售和分销用于肿瘤学研究的高质量抗癌小分子试剂。我们的使命是建立世界上全面的抗癌小分子集合。我们还为制药行业，医学研究组织和学术机构提供高质量的研究服务。我们致力于以具有竞争力的价格提供服务和分子。MedKoo是您可靠的药物发现和药物分子采购合作伙伴。

CRISPR-Cas9是近年兴起的用于靶向基因组特定位置，进行DNA修饰的重要工具。研究发现CRISPR是细菌为了应对病毒的攻击而演化而来的获得性免疫防御机制。具体来说，在CRISPR和Cas9的作用下，经由小RNA分子的引导，靶向并沉默入侵者遗传物质核酸的关键部分。在该系统中，crRNA（CRISPR-derivedRNA）与tracrRNA（trans-activatingRNA）结合形成的复合物能特异性识别靶基因序列，并引导Cas9核酸内切酶在靶定位点剪切双链DNA，随后，细胞的非同源末端连接修复机制（NHEJ）重新连接断裂处的基因组DNA，并引入插入或缺失突变。另外也可以提供一个外源双链供体DNA（Donor）通过同源重组（HR）整合进断裂处的基因组，从而达到对基因组DNA进行修饰的目的。
目前，CRISPR-Cas9系统的高效基因组编辑功能已被应用于多种生物，包括小鼠、大鼠、斑马鱼、秀丽隐杆线虫，也包含多种细菌和植物，甚至在人体上也有应用。