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Details

Stereochemistry ABSOLUTE
Molecular Formula C18H19N5O4S
Molecular Weight 401.44
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VOSAROXIN

SMILES

CN[C@H]1CN(C[C@@H]1OC)C2=CC=C3C(=O)C(=CN(C4=NC=CS4)C3=N2)C(O)=O

InChI

InChIKey=XZAFZXJXZHRNAQ-STQMWFEESA-N
InChI=1S/C18H19N5O4S/c1-19-12-8-22(9-13(12)27-2)14-4-3-10-15(24)11(17(25)26)7-23(16(10)21-14)18-20-5-6-28-18/h3-7,12-13,19H,8-9H2,1-2H3,(H,25,26)/t12-,13-/m0/s1

HIDE SMILES / InChI

Molecular Formula C18H19N5O4S
Molecular Weight 401.44
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created using several sources including: https://www.ncbi.nlm.nih.gov/pubmed/15056007

Vosaroxin is a small molecule and a naphthyridine analogue with antineoplastic activity. This quinolone-based topoisomerase II inhibitor is a new therapeutic for acute myeloid leukemia (AML). Being a DNA intercalating topoisomerase II inhibitor that causes the induction of apoptosis via double-strand DNA breaks vosoroxin is chemically distinct from other topoisomerase inhibitors with its stable quinolone-based core. Due to the stability of this core, vosaroxin is not associated with significant formation of toxic metabolites, free radicals, or reactive oxygen species, which are associated with off-target organ damage and cardiotoxicity. Furthermore, vosaroxin evades two common mechanisms of drug resistance, as it is not a substrate for the P-glycoprotein efflux pump and its activity is maintained in cells with p53 deletion. Vosaroxin has beeт tested in several investigator-sponsored studies, both as a single-agent and in combination with other therapies, for the treatment of AML and myelodysplastic syndromes. Both the U.S. Food and Drug Administration (FDA) and European Commission have granted orphan drug designation to vosaroxin for the treatment of AML. Additionally, vosaroxin has been granted fast track designation by the FDA for the potential treatment of relapsed or refractory AML in combination with cytarabine. Vosaroxin is an investigational drug that has not been approved for use in any jurisdiction. The trademark name QINPREZO is conditionally accepted by the FDA and the EMA as the proprietary name for the vosaroxin drug product candidate.

CNS Activity

Curator's Comment: Radiolabeling experiments in mice indicate that vosaroxin crosses the blood–brain barrier

Originator

Curator's Comment: In 2003 Sunesis licensed worldwide development and commercialization rights to vosaroxin from Sumitomo Dainippon Pharma Co., Ltd. (http://www.sunesis.com/ongoing-partnerships.php)

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Synthesis and structure-activity relationships of novel 7-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids as antitumor agents. Part 2.
2004 Apr 8
SNS-595, a naphthyridine cell cycle inhibitor and stimulator of apoptosis for the treatment of cancers.
2008 Jun
Voreloxin, a first-in-class anticancer quinolone derivative, in relapsed/refractory solid tumors: a report on two dosing schedules.
2010 Apr 1
Voreloxin, a first-in-class anticancer quinolone derivative, acts synergistically with cytarabine in vitro and induces bone marrow aplasia in vivo.
2010 Oct
A phase Ib study of vosaroxin, an anticancer quinolone derivative, in patients with relapsed or refractory acute leukemia.
2011 Dec
Vosaroxin : a novel antineoplastic quinolone.
2012 Aug
Molecular and Pharmacologic Properties of the Anticancer Quinolone Derivative Vosaroxin: A New Therapeutic Agent for Acute Myeloid Leukemia.
2016 Sep
Patents

Sample Use Guides

Voreloxin was administered at a dose of 48 mg/m2 by short intravenous infusion over 10 minutes once every 3 weeks for up to six cycles.
Route of Administration: Intravenous
In vitro toxicity assays were performed on primary AML mononuclear cells. Cells were treated with voreloxin (31.25 nM to 4 M) by serial dilution and incubated for 48 h.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:53:26 GMT 2023
Edited
by admin
on Fri Dec 15 15:53:26 GMT 2023
Record UNII
K6A90IIZ19
Record Status Validated (UNII)
Record Version
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Name Type Language
VOSAROXIN
INN   MART.   USAN   WHO-DD  
INN   USAN  
Official Name English
VOSAROXIN [MART.]
Common Name English
SNS-595
Code English
Vosaroxin [WHO-DD]
Common Name English
(+)-7-((3S,4S)-3-METHOXY-4-(METHYLAMINO)PYRROLIDIN-1-YL)-4-OXO-1-(THIAZOL-2-YL)-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID
Systematic Name English
VORELOXIN
Common Name English
VOSAROXIN [USAN]
Common Name English
1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID, 1,4-DIHYDRO-7-((3S,4S)-3-METHOXY-4-(METHYLAMINO)-1-PYRROLIDINYL)-4-OXO-1-(2-THIAZOLYL)-
Common Name English
vosaroxin [INN]
Common Name English
AG-7352
Code English
SPC-595
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 294509
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
EU-Orphan Drug EU/3/12/990
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
NCI_THESAURUS C259
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
WHO-ATC L01XX53
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
NCI_THESAURUS C795
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID50938662
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
DRUG BANK
DB11999
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
PUBCHEM
9952884
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
WIKIPEDIA
Vosaroxin
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
ChEMBL
CHEMBL68117
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
EVMPD
SUB76117
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
SMS_ID
100000137627
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
USAN
SS-107
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
MESH
C485113
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
CAS
175414-77-4
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
INN
9066
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
FDA UNII
K6A90IIZ19
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
NCI_THESAURUS
C95148
Created by admin on Fri Dec 15 15:53:26 GMT 2023 , Edited by admin on Fri Dec 15 15:53:26 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
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ACTIVE MOIETY