Quisinostat HCl
featured

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

MedKoo CAT#: 201612

CAS#: 875320-31-3 (2HCl)

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.


Chemical Structure

img
Quisinostat HCl
CAS# 875320-31-3 (2HCl)

Theoretical Analysis

MedKoo Cat#: 201612
Name: Quisinostat HCl
CAS#: 875320-31-3 (2HCl)
Chemical Formula: C21H28Cl2N6O2
Exact Mass: 394.21172
Molecular Weight: 467.4
Elemental Analysis: C, 53.97; H, 6.04; Cl, 15.17; N, 17.98; O, 6.85

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 750.0 Ready to ship
200.0mg USD 1150.0 Ready to ship
500.0mg USD 1950.0 Ready to ship
1.0g USD 2950.0 Ready to ship
2.0g USD 5250.0 Ready to ship
Click to view more sizes and prices
Bulk inquiry

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; quisinostat dihydrochloride;

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

InChi Key: NRUIZESXVMJDKR-UHFFFAOYSA-N

InChi Code: InChI=1S/C21H26N6O2.2ClH/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);2*1H

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

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Quisinostat dihydrochloride (JNJ-26481585 dihydrochloride) is a potent pan-HDAC inhibitor with IC50s of 0.11 nM, 0.33 nM, 0.64 nM, 0.46 nM, and 0.37 nM for HDAC1, HDAC2, HDAC4, HDAC10 and HDAC11, respectively.
In vitro activity: Flow cytometry analysis was performed to explore mechanism of cell cycle arrest induced by quisinostat. As shown in Figure 3A-B, in contrast to DMSO group, it was observed that quisinostat substantially induced G0/G1 phase arrest both in HCCLM3 and SMMC7721 cells. Moreover, in order to verify the influence of quisinostat on cell cycle arrest, expressions of p21, cdk2, cdk4, cdk6, cyclinD1, cyclinE1 and cyclinA2 were detected by Western blotting (Fig.3C-D). Consequently the results supported that quisinostat did play a role in G0/G1 cell cycle arrest by upregulating expression of p21 as well as downregulating levels of cdk2/cdk4/cdk6/ cyclinD1/cyclinE1/cyclinA2 proteins. Accordingly apoptosis assay demonstrated that quisinostat could facilitate apoptosis in HCC cells more effectively when compared with DMSO group (Fig.4A-B). In agreement with the data of apoptosis assay, quisinostat enhanced expression levels of proapoptosis proteins, cleaved-Caspase-3, cleaved-Caspase-9, cleaved-PARP and Bax and decreased levels of antiapoptosis proteins, Bcl-xl, Bcl2 and survivin in HCC cells in contrast to DMSO group (Fig.4C). The findings suggested that quisinostat induced apoptotic events both in HCCLM3 and SMMC-7721 cells. Our study indicated that quisinostat, as a novel chemotherapy for HCC, exhibited excellent antitumor activity in vitro. Int J Biol Sci. 2018; 14(13): 1845–1858. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231215/
In vivo activity: JNJ-26481585 administered continuously for 14 days (once daily, 10 mg/kg i.p.) in male nude mice strongly inhibited the growth of large pre-established HCT116 colon xenografts (320 ± 10 mm3 at start of treatment). At the end of the study, JNJ-26481585 inhibited tumor volume by 76% (treated versus control = 24), which is superior to the activity of the clinical standard of care agent 5-FU (41% inhibition). In agreement with its low antitumor potency, vorinostat only slightly increased H3 acetylation levels at 4 hours postdose (0.03 ± 0.02 ng/μg protein), whereas JNJ-26481585 showed a more potent effect (0.22 ± 0.07 ng/μg protein; data not shown). A subsequent dose-response study to further explore the potency of JNJ-26481585 showed similar tumor growth inhibition at 5 mg/kg compared with 20 mg/kg (87% and 93% inhibition, respectively, Fig. 6B), whereas half-maximal inhibition was obtained at the low dose of 2.5 mg/kg in the pre-established setting (69% inhibition). JNJ-26481585 was also tested in a C170HM2 colorectal liver metastasis model. As shown in Fig. 6D, there was a significant 87% reduction in mean liver tumor burden in the JNJ-26481585– treated group (0.380 g reduced to 0.050 g; P = 0.016). Clin Cancer Res. 2009 Nov 15;15(22):6841-51. https://clincancerres.aacrjournals.org/content/15/22/6841.long

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 46.7 99.9

Preparing Stock Solutions

The following data is based on the product molecular weight 467.4 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. 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 "secondgeneration" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res. 2009 Nov 15;15(22):6841-51. doi: 10.1158/1078-0432.CCR-09-0547. Epub 2009 Oct 27. PMID: 19861438. 2. He B, Dai L, Zhang X, Chen D, Wu J, Feng X, Zhang Y, Xie H, Zhou L, Wu J, Zheng S. The HDAC Inhibitor Quisinostat (JNJ26481585) Supresses Hepatocellular Carcinoma alone and Synergistically in Combination with Sorafenib by G0/G1 phase arrest and Apoptosis induction. Int J Biol Sci. 2018 Oct 20;14(13):1845-1858. doi: 10.7150/ijbs.27661. PMID: 30443188; PMCID: PMC6231215 3.Capasso KE, Manners MT, Quershi RA, Tian Y, Gao R, Hu H, Barrett JE, Sacan A, Ajit SK. Effect of histone deacetylase inhibitor JNJ-26481585 in pain. J Mol Neurosci. 2015 Mar;55(3):570-8. doi: 10.1007/s12031-014-0391-7. Epub 2014 Aug 2. PMID: 25085711. 4. 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 "secondgeneration" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res. 2009 Nov 15;15(22):6841-51. doi: 10.1158/1078-0432.CCR-09-0547. Epub 2009 Oct 27. PMID: 19861438.
In vitro protocol: 1. 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 "secondgeneration" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res. 2009 Nov 15;15(22):6841-51. doi: 10.1158/1078-0432.CCR-09-0547. Epub 2009 Oct 27. PMID: 19861438. 2. He B, Dai L, Zhang X, Chen D, Wu J, Feng X, Zhang Y, Xie H, Zhou L, Wu J, Zheng S. The HDAC Inhibitor Quisinostat (JNJ26481585) Supresses Hepatocellular Carcinoma alone and Synergistically in Combination with Sorafenib by G0/G1 phase arrest and Apoptosis induction. Int J Biol Sci. 2018 Oct 20;14(13):1845-1858. doi: 10.7150/ijbs.27661. PMID: 30443188; PMCID: PMC6231215
In vivo protocol: 1. Capasso KE, Manners MT, Quershi RA, Tian Y, Gao R, Hu H, Barrett JE, Sacan A, Ajit SK. Effect of histone deacetylase inhibitor JNJ-26481585 in pain. J Mol Neurosci. 2015 Mar;55(3):570-8. doi: 10.1007/s12031-014-0391-7. Epub 2014 Aug 2. PMID: 25085711. 2. 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 "secondgeneration" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res. 2009 Nov 15;15(22):6841-51. doi: 10.1158/1078-0432.CCR-09-0547. Epub 2009 Oct 27. PMID: 19861438.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

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

2: Maes K, De Smedt E, Lemaire M, De Raeve H, Menu E, Van Valckenborgh E, McClue S, Vanderkerken K, De Bruyne E. The role of DNA damage and repair 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, Reynolds CP, Kang MH, Maris JM, Wozniak A, Hickson I, Lyalin D, Kurmasheva RT, Houghton PJ, Smith MA, Lock R. 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. 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 of quisinostat (JNJ-26481585), an oral hydroxamate histone deacetylase inhibitor with evidence of target modulation and antitumor activity, in patients with advanced solid tumors. Clin Cancer Res. 2013 Aug 1;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 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. PubMed PMID: 23073311; PubMed Central PMCID: PMC3658191.

6: Stühmer T, Arts J, Chatterjee M, Borawski J, Wolff A, King P, Einsele H, Leo E, Bargou RC. 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. 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, 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 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, 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. PubMed PMID: 19682743.

9: Deleu S, Lemaire M, Arts J, Menu E, Van Valckenborgh E, Vande Broek I, De Raeve H, Coulton L, Van Camp B, Croucher P, Vanderkerken K. Bortezomib alone or in combination with the histone deacetylase inhibitor JNJ-26481585: effect on myeloma bone disease in the 5T2MM murine 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. The effects of JNJ-26481585, a novel hydroxamate-based histone deacetylase inhibitor, on the development of multiple myeloma in the 5T2MM and 5T33MM 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 histone acetylation 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).



Additional Information

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