QUISINOSTAT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H26N6O2
Molecular Weight	394.4701
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C=C(CNCC2CCN(CC2)C3=NC=C(C=N3)C(=O)NO)C4=C1C=CC=C4

InChI

InChIKey=PAWIYAYFNXQGAP-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.newvac.ru/produkty/quisinostat.html | https://www.ncbi.nlm.nih.gov/pubmed/19861438 | https://www.ncbi.nlm.nih.gov/pubmed/26836950 | https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=596704

Quisinostat is an orally bioavailable potent histone deacetylase inhibitor, specifically selected due to its sustained inhibition of HDAC1 in solid tumor tissues and prolonged period of half-elimination from tissues. Phase 2 clinical trials are ongoing in patients with platinum-resistant ovarian cancer and non-small cell lung cancer (NSCLC). Quisinostat is active in the treatment of patients with relapsed or refractory Sézary syndrome. The most common drug-related adverse events reported in this trial were: nausea, diarrhea, asthenia. Grade 3 adverse events were also reported: hypertension, lethargy and pruritus.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histone deacetylase 1 51 Target ID: CHEMBL325 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19861438	Inhibitor 8297	0.11 nM [IC50]
Histone deacetylase 2 37 Target ID: CHEMBL1937 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19861438	Inhibitor 8297	0.33 nM [IC50]
Histone deacetylase 11 8 Target ID: CHEMBL3310 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19861438	Inhibitor 8297	0.37 nM [IC50]
Histone deacetylase 10 10 Target ID: CHEMBL5103 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19861438	Inhibitor 8297	0.46 nM [IC50]
Histone deacetylase 4 11 Target ID: CHEMBL3524 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19861438	Inhibitor 8297	0.64 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Sezary syndrome 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26836950	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: http://adisinsight.springer.com/drugs/800027268	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27423454	Primary	Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681266	inconclusive [IC50 23.9185 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681266	no
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006335	yes [IC50 1.049 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681266	yes [IC50 3.3786 uM]

Sourcing

Vendor/Aggregator	ID	URL
Aaron Chemicals	AR00H2B1	http://www.aaronchem.com/875320-31-3
Angel Pharmatech	AG-12167	http://www.angelpharmatech.com/1083078-98-1.html
Chemspace	CSSB00159266828	https://chem-space.com/CSSB00159266828
Excenen	EX-A667	http://www.excenen.com/searchresultlist.php?id=875320-29-9
Lan Pharmatech	LAN-B70589
MolPort	MolPort-047-117-231	https://www.molport.com/shop/molecule-link/MolPort-047-117-231
MuseChem	I008947	https://www.musechem.com/product/I008947.html
Smolecule	S548185	http://www.smolecule.com/products/s548185
THE BioTek	bt-287592	https://www.thebiotek.com/product/inhibitors/bt-287592
THE BioTek	bt-399567	https://www.thebiotek.com/product/others/bt-399567
eNovation Chemicals	D672997	https://www.enovationchem.com/ProductDetails.asp?ProductID=D672997

PubMed

Title	Date	PubMed
Bortezomib alone or in combination with the histone deacetylase inhibitor JNJ-26481585: effect on myeloma bone disease in the 5T2MM murine model of myeloma.	2009 Jul 1	19531653
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.	2009 Jun	19322073
JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity.	2009 Nov 15	19861438
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.	2009 Oct	19494837
Preclinical antileukemia activity of JNJ-26481585, a potent second-generation histone deacetylase inhibitor.	2010 Feb	19682743
Preclinical anti-myeloma activity of the novel HDAC-inhibitor JNJ-26481585.	2010 May	20331455
Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors.	2011 Jul 14	21650221

Patents

Sample Use Guides

In Vivo Use Guide

12 mg capsule on days 1, 3, and 5 of each week in a 21-day treatment cycle

Route of Administration: Oral

In Vitro Use Guide

Quisinostat inhibited cell proliferation in all lung, breast, colon, prostate, brain, and ovarian tumor cell lines tested, with IC50 values ranging from 3.1 to 246 nM/L.

Name

Type

Language

QUISINOSTAT

Official Name

English

JNJ-26481585

Code

English

Quisinostat [WHO-DD]

Common Name

English

N-Hydroxy-2-[4-({[(1-methyl-1H-indol-3-yl)methyl]amino}methyl)piperidin-1-yl]pyrimidine-5-carboxamide

Systematic Name

English

quisinostat [INN]

Common Name

English

QUISINOSTAT [USAN]

Common Name

English

5-PYRIMIDINECARBOXAMIDE, N-HYDROXY-2-(4-((((1-METHYL-1H-INDOL-3-YL)METHYL)AMINO)METHYL)-1-PIPERIDINYL)-

Systematic Name

English

JNJ 26481585

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1946