Quisinostat | CAS#875320-29-9 | histone deacetylase inhibitor

MedKoo Cat#: 596245 | Name: Quisinostat

Featured

Description:

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

Quisinostat (USAN; development code JNJ-26481585) is an experimental drug candidate for the treatment of cancer. It is a "second generation" histone deacetylase inhibitor with antineoplastic activity. Quisinostat is highly potent against class I and II HDACs.

Chemical Structure

Quisinostat

CAS#875320-29-9 (free base)

Theoretical Analysis

MedKoo Cat#: 596245

Name: Quisinostat

CAS#: 875320-29-9 (free base)

Chemical Formula: C21H26N6O2

Exact Mass: 394.2117

Molecular Weight: 394.48

Elemental Analysis: C, 63.94; H, 6.64; N, 21.30; O, 8.11

Price and Availability

Size	Price	Availability
5mg	USD 350.00	2 weeks
10mg	USD 650.00	2 weeks
50mg	USD 1,250.00	2 weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

1083078-98-1 (HCl) 875320-29-9 (free base) 875320-31-3 (2HCl)

Synonym

Quisinostat; JNJ-26481585; JNJ 26481585; JNJ26481585;

IUPAC/Chemical Name

N-hydroxy-2-(4-((((1-methyl-1H-indol-3-yl)methyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxamide

InChi Key

PAWIYAYFNXQGAP-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H26N6O2/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)

SMILES Code

O=C(C1=CN=C(N2CCC(CNCC3=CN(C)C4=C3C=CC=C4)CC2)N=C1)NO

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

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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Quisinostat is a second-generation, orally active pan-HDAC inhibitor, with IC50 values from 0.11 nM to 0.64 nM for HDAC1, HDAC2, HDAC4, HDAC10 and HDAC11.

In vitro activity:

This study investigated the effect of Quisinostat on neuroblastoma SK-N-SH cells differentiation. Quisinostat induces differentiation in SK-N-SH cells. This study also observed that autophagy plays an important role in Quisinostat induced cell differentiation of SK-N-SH cells. Autophagy is induced upon Quisinostat treatment and is important for the neuronal differentiation of human SK-N-SH cells. Reference: Mol Biol Rep. 2021 May;48(5):4973-4979. https://pubmed.ncbi.nlm.nih.gov/34125328/

In vivo activity:

Quisinostat inhibits osteoclast differentiation in vitro and protects mice from titanium particle-induced osteolysis in vivo. This study demonstrated that Quisinostat can ameliorate estrogen deficiency-induced osteoporosis by inhibiting bone resorption and promoting bone formation; this is the first evidence to support Quisinostat as a potential therapeutic agent for postmenopausal osteoporosis prevention and treatment.. Reference: Eur J Pharmacol. 2022 Jul 15;927:175073. https://pubmed.ncbi.nlm.nih.gov/35636521/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	126.75

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 394.48 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. 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. 2. Kommalapati VK, Kumar D, Tangutur AD. Quisinostat mediated autophagy is associated with differentiation in neuroblastoma SK-N-SH cells. Mol Biol Rep. 2021 May;48(5):4973-4979. doi: 10.1007/s11033-021-06481-z. Epub 2021 Jun 14. PMID: 34125328. 3. 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. 4. Mao L, Liu L, Zhang T, Qin H, Wu X, Xu Y. Histone Deacetylase 11 Contributes to Renal Fibrosis by Repressing KLF15 Transcription. Front Cell Dev Biol. 2020 Apr 17;8:235. doi: 10.3389/fcell.2020.00235. PMID: 32363192; PMCID: PMC7180197.

In vitro protocol:

In vivo protocol:

1. 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. 2. Mao L, Liu L, Zhang T, Qin H, Wu X, Xu Y. Histone Deacetylase 11 Contributes to Renal Fibrosis by Repressing KLF15 Transcription. Front Cell Dev Biol. 2020 Apr 17;8:235. doi: 10.3389/fcell.2020.00235. PMID: 32363192; PMCID: PMC7180197.

1: Enßle JC, Boedicker C, Wanior M, Vogler M, Knapp S, Fulda S. Co-targeting of BET proteins and HDACs as a novel approach to trigger apoptosis in rhabdomyosarcoma cells. Cancer Lett. 2018 Apr 27;428:160-172. doi: 10.1016/j.canlet.2018.04.032. [Epub ahead of print] PubMed PMID: 29709701. 2: Samiec M, Skrzyszowska M. Intrinsic and extrinsic molecular determinants or modulators for epigenetic remodeling and reprogramming of somatic cell-derived genome in mammalian nuclear-transferred oocytes and resultant embryos. Pol J Vet Sci. 2018 Mar;21(1):217-227. doi: 10.24425/119040. PubMed PMID: 29624006. 3: Householder KT, DiPerna DM, Chung EP, Luning AR, Nguyen DT, Stabenfeldt SE, Mehta S, Sirianni RW. pH driven precipitation of quisinostat onto PLA-PEG nanoparticles enables treatment of intracranial glioblastoma. Colloids Surf B Biointerfaces. 2018 Jun 1;166:37-44. doi: 10.1016/j.colsurfb.2018.02.048. Epub 2018 Feb 24. PubMed PMID: 29533842. 4: Heijkants R, Willekens K, Schoonderwoerd M, Teunisse A, Nieveen M, Radaelli E, Hawinkels L, Marine JC, Jochemsen A. Combined inhibition of CDK and HDAC as a promising therapeutic strategy for both cutaneous and uveal metastatic melanoma. Oncotarget. 2017 Dec 15;9(5):6174-6187. doi: 10.18632/oncotarget.23485. eCollection 2018 Jan 19. PubMed PMID: 29464063; PubMed Central PMCID: PMC5814203. 5: Sixto-López Y, Bello M, Correa-Basurto J. Insights into structural features of HDAC1 and its selectivity inhibition elucidated by Molecular dynamic simulation and Molecular Docking. J Biomol Struct Dyn. 2018 Mar 6:1-27. doi: 10.1080/07391102.2018.1441072. [Epub ahead of print] PubMed PMID: 29447615. 6: Laporte AN, Poulin NM, Barrott JJ, Wang XQ, Lorzadeh A, Vander Werff R, Jones KB, Underhill TM, Nielsen TO. Death by HDAC Inhibition in Synovial Sarcoma Cells. Mol Cancer Ther. 2017 Dec;16(12):2656-2667. doi: 10.1158/1535-7163.MCT-17-0397. Epub 2017 Sep 6. PubMed PMID: 28878027. 7: Li F, Wang T, Wang Z, Chen X, Liu R. Histone deacetylase inhibitor quisinostat activates caspase signaling and upregulates p53 acetylation to inhibit the proliferation of HepG2 cells. Mol Med Rep. 2017 Nov;16(5):6094-6101. doi: 10.3892/mmr.2017.7355. Epub 2017 Aug 24. PubMed PMID: 28849080. 8: Haydn T, Metzger E, Schuele R, Fulda S. Concomitant epigenetic targeting of LSD1 and HDAC synergistically induces mitochondrial apoptosis in rhabdomyosarcoma cells. Cell Death Dis. 2017 Jun 15;8(6):e2879. doi: 10.1038/cddis.2017.239. PubMed PMID: 28617441; PubMed Central PMCID: PMC5520898. 9: Jin L, Guo Q, Zhu HY, Xing XX, Zhang GL, Xuan MF, Luo QR, Luo ZB, Wang JX, Yin XJ, Kang JD. Quisinostat treatment improves histone acetylation and developmental competence of porcine somatic cell nuclear transfer embryos. Mol Reprod Dev. 2017 Apr;84(4):340-346. doi: 10.1002/mrd.22787. Epub 2017 Mar 6. PubMed PMID: 28224725. 10: Laporte AN, Barrott JJ, Yao RJ, Poulin NM, Brodin BA, Jones KB, Underhill TM, Nielsen TO. HDAC and Proteasome Inhibitors Synergize to Activate Pro-Apoptotic Factors in Synovial Sarcoma. PLoS One. 2017 Jan 5;12(1):e0169407. doi: 10.1371/journal.pone.0169407. eCollection 2017. PubMed PMID: 28056055; PubMed Central PMCID: PMC5215898. 11: Bao L, Diao H, Dong N, Su X, Wang B, Mo Q, Yu H, Wang X, Chen C. Histone deacetylase inhibitor induces cell apoptosis and cycle arrest in lung cancer cells via mitochondrial injury and p53 up-acetylation. Cell Biol Toxicol. 2016 Dec;32(6):469-482. Epub 2016 Jul 16. PubMed PMID: 27423454; PubMed Central PMCID: PMC5099365. 12: Wang JG, Cai Q, Zheng J, Dong YS, Li JJ, Li JC, Hao GZ, Wang C, Wang JL. Epigenetic Suppression of GADs Expression is Involved in Temporal Lobe Epilepsy and Pilocarpine-Induced Mice Epilepsy. Neurochem Res. 2016 Jul;41(7):1751-60. doi: 10.1007/s11064-016-1891-3. Epub 2016 May 25. PubMed PMID: 27220336. 13: Child F, Ortiz-Romero PL, Alvarez R, Bagot M, Stadler R, Weichenthal M, Alves R, Quaglino P, Beylot-Barry M, Cowan R, Geskin LJ, Pérez-Ferriols A, Hellemans P, Elsayed Y, Phelps C, Forslund A, Kamida M, Zinzani PL. Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sézary syndrome. Br J Dermatol. 2016 Jul;175(1):80-8. doi: 10.1111/bjd.14427. Epub 2016 Jun 2. PubMed PMID: 26836950. 14: Moreau P, Facon T, Touzeau C, Benboubker L, Delain M, Badamo-Dotzis J, Phelps C, Doty C, Smit H, Fourneau N, Forslund A, Hellemans P, Leleu X. Quisinostat, bortezomib, and dexamethasone combination therapy for relapsed multiple myeloma. Leuk Lymphoma. 2016 Jul;57(7):1546-59. doi: 10.3109/10428194.2015.1117611. Epub 2016 Jan 12. PubMed PMID: 26758913. 15: Heinicke U, Kupka J, Fichter I, Fulda S. Critical role of mitochondria-mediated apoptosis for JNJ-26481585-induced antitumor activity in rhabdomyosarcoma. Oncogene. 2016 Jul 14;35(28):3729-41. doi: 10.1038/onc.2015.440. Epub 2015 Nov 30. PubMed PMID: 26616861. 16: Heinicke U, Kupka J, Fulda S. JNJ-26481585 primes rhabdomyosarcoma cells for chemotherapeutics by engaging the mitochondrial pathway of apoptosis. Oncotarget. 2015 Nov 10;6(35):37836-51. doi: 10.18632/oncotarget.6097. PubMed PMID: 26473375; PubMed Central PMCID: PMC4741969. 17: Qureshi RA, Tian Y, McDonald MK, Capasso KE, Douglas SR, Gao R, Orlova IA, Barrett JE, Ajit SK, Sacan A. Circulating microRNA Signatures in Rodent Models of Pain. Mol Neurobiol. 2016 Jul;53(5):3416-3427. doi: 10.1007/s12035-015-9281-4. Epub 2015 Jun 18. PubMed PMID: 26081151. 18: Johansson C, Jamal Fattah T, Yu H, Nygren J, Mossberg AK, Schwartz S. Acetylation of intragenic histones on HPV16 correlates with enhanced HPV16 gene expression. Virology. 2015 Aug;482:244-59. doi: 10.1016/j.virol.2015.02.053. Epub 2015 Apr 17. PubMed PMID: 25900886. 19: Wang EC, Min Y, Palm RC, Fiordalisi JJ, Wagner KT, Hyder N, Cox AD, Caster JM, Tian X, Wang AZ. Nanoparticle formulations of histone deacetylase inhibitors for effective chemoradiotherapy in solid tumors. Biomaterials. 2015 May;51:208-215. doi: 10.1016/j.biomaterials.2015.02.015. Epub 2015 Feb 19. PubMed PMID: 25771011; PubMed Central PMCID: PMC4361776. 20: Ashjian E, Redic K. Multiple myeloma: Updates for pharmacists in the treatment of relapsed and refractory disease. J Oncol Pharm Pract. 2016 Apr;22(2):289-302. doi: 10.1177/1078155215572036. Epub 2015 Feb 17. Review. PubMed PMID: 25694345.

View History

Fulzerasib

MedKoo CAT#: 130281

CAS#: 2641747-54-6