Quisinostat hydrochloride | JNJ-26481585 | CAS#875320-31-3 | 1083078-98-1 | 875320-29-9 | HDAC inhibitor

MedKoo Cat#: 201612 | Name: Quisinostat HCl

Description:

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

Quisinostat, also known as JNJ-26481585, is an orally bioavailable, second-generation, hydroxamic acid-based inhibitor of histone deacetylase (HDAC) with potential antineoplastic activity. 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

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: 0.0000

Molecular Weight: 467.40

Elemental Analysis: C, 53.97; H, 6.04; Cl, 15.17; N, 17.98; O, 6.85

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,850.00	Ready to ship
1g	USD 3,850.00	Ready to ship
2g	USD 6,450.00	Ready to ship

Bulk Inquiry

Buy Now

Add to Cart

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

More Info

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# A21T03K10

QC Data

View QC data: current batch, Lot# A21T03K10

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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

	Solvent	mg/mL	mM
Solubility
	DMSO	20.0	42.79
	DMF	25.0	53.49
	Ethanol	1.5	3.21

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 467.40 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.

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:

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.

1: Tajer P, Karakaslar EO, Canté-Barrett K, Naber B, Vloemans S, Eggermond MV, van der Hoorn ML, van den Akker EB, Pike-Overzet K, Staal FJ. Utilizing Epigenetic Regulators to improve HSC-based lentiviral gene therapy. Blood Adv. 2024 Jun 25:bloodadvances.2024013047. doi: 10.1182/bloodadvances.2024013047. Epub ahead of print. PMID: 38916861. 2: Müller MR, Burmeister A, Skowron MA, Stephan A, Söhngen C, Wollnitzke P, Petzsch P, Alves Avelar LA, Kurz T, Köhrer K, Levkau B, Nettersheim D. Characterization of the dehydrogenase-reductase DHRS2 and its involvement in histone deacetylase inhibition in urological malignancies. Exp Cell Res. 2024 Jun 1;439(1):114055. doi: 10.1016/j.yexcr.2024.114055. Epub 2024 May 3. PMID: 38704080. 3: Meneceur S, De Vos CE, Petzsch P, Köhrer K, Niegisch G, Hoffmann MJ. New synergistic combination therapy approaches with HDAC inhibitor quisinostat, cisplatin or PARP inhibitor talazoparib for urothelial carcinoma. J Cell Mol Med. 2024 May;28(9):e18342. doi: 10.1111/jcmm.18342. PMID: 38693852; PMCID: PMC11063726. 4: Zhang W, Oh JH, Zhang W, Aldrich CC, Sirianni RW, Elmquist WF. Central Nervous System Distributional Kinetics of Selected Histone Deacetylase Inhibitors. J Pharmacol Exp Ther. 2024 Apr 26:JPET-AR-2024-002170. doi: 10.1124/jpet.124.002170. Epub ahead of print. PMID: 38670802. 5: Zhou L, Wu Y, Ying Y, Ding Y. Current knowledge of ferroptosis in the pathogenesis and prognosis of oral squamous cell carcinoma. Cell Signal. 2024 Jul;119:111176. doi: 10.1016/j.cellsig.2024.111176. Epub 2024 Apr 16. PMID: 38636767. 6: Ri-Wen, Yang YH, Zhang TN, Liu CF, Yang N. Targeting epigenetic and post- translational modifications regulating pyroptosis for the treatment of inflammatory diseases. Pharmacol Res. 2024 May;203:107182. doi: 10.1016/j.phrs.2024.107182. Epub 2024 Apr 12. PMID: 38614373. 7: Kim U, Debnath R, Maiz JE, Rico J, Sinha S, Blanco MA, Chakrabarti R. ΔNp63 regulates MDSC survival and metabolism in triple-negative breast cancer. iScience. 2024 Feb 29;27(4):109366. doi: 10.1016/j.isci.2024.109366. PMID: 38510127; PMCID: PMC10951988. 8: Ishii D, Shindo Y, Arai W, Konno T, Kohno T, Honda K, Miyajima M, Watanabe A, Kojima T. The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells. Int J Mol Sci. 2024 Jan 24;25(3):1411. doi: 10.3390/ijms25031411. PMID: 38338691; PMCID: PMC10855320. 9: Lo Cascio C, Margaryan T, Luna-Melendez E, McNamara JB, White CI, Knight W, Ganta S, Opachich Z, Cantoni C, Yoo W, Sanai N, Tovmasyan A, Mehta S. Quisinostat is a brain-penetrant radiosensitizer in glioblastoma. JCI Insight. 2023 Nov 22;8(22):e167081. doi: 10.1172/jci.insight.167081. PMID: 37991020; PMCID: PMC10721329. 10: Noll A, Myers C, Biery MC, Meechan M, Tahiri S, Rajendran A, Berens ME, Paine D, Byron S, Zhang J, Winter C, Pakiam F, Leary SES, Cole BL, Jackson ER, Dun MD, Foster JB, Evans MK, Pattwell SS, Olson JM, Vitanza NA. Therapeutic HDAC inhibition in hypermutant diffuse intrinsic pontine glioma. Neoplasia. 2023 Sep;43:100921. doi: 10.1016/j.neo.2023.100921. Epub 2023 Aug 19. PMID: 37603953; PMCID: PMC10465940. 11: Wang Z, Muthusamy V, Petrylak DP, Anderson KS. Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy. NPJ Precis Oncol. 2023 Jul 21;7(1):70. doi: 10.1038/s41698-023-00417-5. PMID: 37479885; PMCID: PMC10362036. 12: Groenewoud A, Yin J, Gelmi MC, Alsafadi S, Nemati F, Decaudin D, Roman-Roman S, Kalirai H, Coupland SE, Jochemsen AG, Jager MJ, Engel FB, Snaar-Jagalska BE. Patient-derived zebrafish xenografts of uveal melanoma reveal ferroptosis as a drug target. Cell Death Discov. 2023 Jun 16;9(1):183. doi: 10.1038/s41420-023-01446-6. PMID: 37321991; PMCID: PMC10272172. 13: Liu HL, Chen HF, Liu QD, Xu WZ, Zhang JJ, He XC, Yan YJ, Ruan Y, Zhou M. HDAC Downregulation of Xiaoqinglong Decoction in the Treatment of Allergic Rhinitis. Int Arch Allergy Immunol. 2023;184(4):376-390. doi: 10.1159/000527429. Epub 2023 Jan 5. PMID: 36603560. 14: Nakano M, Ohwada K, Shindo Y, Konno T, Kohno T, Kikuchi S, Tsujiwaki M, Ishii D, Nishida S, Kakuki T, Obata K, Miyata R, Kurose M, Kondoh A, Takano K, Kojima T. Inhibition of HDAC and Signal Transduction Pathways Induces Tight Junctions and Promotes Differentiation in p63-Positive Salivary Duct Adenocarcinoma. Cancers (Basel). 2022 May 24;14(11):2584. doi: 10.3390/cancers14112584. PMID: 35681564; PMCID: PMC9179926. 15: Sun S, Xiu C, Chai L, Chen X, Zhang L, Liu Q, Chen J, Zhou H. HDAC inhibitor quisinostat prevents estrogen deficiency-induced bone loss by suppressing bone resorption and promoting bone formation in mice. Eur J Pharmacol. 2022 Jul 15;927:175073. doi: 10.1016/j.ejphar.2022.175073. Epub 2022 May 28. PMID: 35636521. 16: Wang M, Tang T, Li R, Huang Z, Ling D, Zheng L, Ding Y, Liu T, Xu W, Zhu F, Min H, Boonhok R, Mao F, Zhu J, Li X, Jiang L, Li J. Drug Repurposing of Quisinostat to Discover Novel Plasmodium falciparum HDAC1 Inhibitors with Enhanced Triple-Stage Antimalarial Activity and Improved Safety. J Med Chem. 2022 Mar 10;65(5):4156-4181. doi: 10.1021/acs.jmedchem.1c01993. Epub 2022 Feb 17. PMID: 35175762. 17: Müller MR, Burmeister A, Skowron MA, Stephan A, Bremmer F, Wakileh GA, Petzsch P, Köhrer K, Albers P, Nettersheim D. Therapeutical interference with the epigenetic landscape of germ cell tumors: a comparative drug study and new mechanistical insights. Clin Epigenetics. 2022 Jan 7;14(1):5. doi: 10.1186/s13148-021-01223-1. PMID: 34996497; PMCID: PMC8742467. 18: Chowdhury A, Marin A, Weber DJ, Andrianov AK. Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities. Pharmaceutics. 2021 Nov 2;13(11):1834. doi: 10.3390/pharmaceutics13111834. PMID: 34834249; PMCID: PMC8619266. 19: Xia N, Tenzer S, Lunov O, Karl M, Simmet T, Daiber A, Münzel T, Reifenberg G, Förstermann U, Li H. Regulation of NADPH Oxidase-Mediated Superoxide Production by Acetylation and Deacetylation. Front Physiol. 2021 Aug 12;12:693702. doi: 10.3389/fphys.2021.693702. PMID: 34456745; PMCID: PMC8387964. 20: Bouché M, Dong YC, Sheikh S, Taing K, Saxena D, Hsu JC, Chen MH, Salinas RD, Song H, Burdick JA, Dorsey J, Cormode DP. Novel Treatment for Glioblastoma Delivered by a Radiation Responsive and Radiopaque Hydrogel. ACS Biomater Sci Eng. 2021 Jul 12;7(7):3209-3220. doi: 10.1021/acsbiomaterials.1c00385. Epub 2021 Jun 23. PMID: 34160196; PMCID: PMC8411482.