QUISINOSTAT

Investigational

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

Molecular Formula	C21H26N6O2
Molecular Weight	394.4701
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 8228	0.11 nM [IC50]
Histone deacetylase 2 37 Target ID: CHEMBL1937 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19861438	Inhibitor 8228	0.33 nM [IC50]
Histone deacetylase 11 8 Target ID: CHEMBL3310 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19861438	Inhibitor 8228	0.37 nM [IC50]
Histone deacetylase 10 10 Target ID: CHEMBL5103 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19861438	Inhibitor 8228	0.46 nM [IC50]
Histone deacetylase 4 11 Target ID: CHEMBL3524 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19861438	Inhibitor 8228	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 1144	Unknown Approved Use Unknown
Ovarian cancer 152 Sources: http://adisinsight.springer.com/drugs/800027268	Primary	Phase II 1144	Unknown Approved Use Unknown
Non-small cell lung cancer 201 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27423454	Primary	Phase I 424	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579	inhibitor 1752	inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1437

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1909	inhibitor 3240 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681266	inconclusive [IC50 23.9185 uM]
CYP2C9 1803	inhibitor 3240 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681266	no
P-gp 1626	inhibitor 3240 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006335	yes [IC50 1.049 uM]
CYP2D6 1875	inhibitor 3240 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

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.

Substance Class	Chemical Created by `admin` on `Thu Jul 06 07:57:39 UTC 2023` Edited by `admin` on `Thu Jul 06 07:57:39 UTC 2023`
Record UNII	9BJ85K1J8S
Record Status	`Validated (UNII)`
Record Version

Download

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