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
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
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 |
DescriptionCurator's Comment: Description was created using several sources including:
https://www.ncbi.nlm.nih.gov/pubmed/15056007
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=27484675
Curator's Comment: Radiolabeling experiments in mice indicate that vosaroxin crosses the blood–brain barrier
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18516764https://www.ncbi.nlm.nih.gov/pubmed/15056007
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
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL2094255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=27484675 |
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Target ID: CHEMBL2094255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21134979 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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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 |
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SNS-595, a naphthyridine cell cycle inhibitor and stimulator of apoptosis for the treatment of cancers. | 2008 Jun |
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Voreloxin, a first-in-class anticancer quinolone derivative, in relapsed/refractory solid tumors: a report on two dosing schedules. | 2010 Apr 1 |
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Voreloxin, a first-in-class anticancer quinolone derivative, acts synergistically with cytarabine in vitro and induces bone marrow aplasia in vivo. | 2010 Oct |
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A phase Ib study of vosaroxin, an anticancer quinolone derivative, in patients with relapsed or refractory acute leukemia. | 2011 Dec |
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Vosaroxin : a novel antineoplastic quinolone. | 2012 Aug |
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Molecular and Pharmacologic Properties of the Anticancer Quinolone Derivative Vosaroxin: A New Therapeutic Agent for Acute Myeloid Leukemia. | 2016 Sep |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21252718
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 Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21134979
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
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admin
on
Edited
Fri Dec 15 15:53:26 GMT 2023
by
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Fri Dec 15 15:53:26 GMT 2023
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Record UNII |
K6A90IIZ19
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Record Status |
Validated (UNII)
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Record Version |
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FDA ORPHAN DRUG |
294509
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EU-Orphan Drug |
EU/3/12/990
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NCI_THESAURUS |
C259
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WHO-ATC |
L01XX53
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NCI_THESAURUS |
C795
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DB11999
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9952884
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Vosaroxin
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CHEMBL68117
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SUB76117
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100000137627
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SS-107
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C485113
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C95148
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ACTIVE MOIETY |