 | |
| Names | |
|---|---|
| Preferred IUPAC name 7-[(3S,4S)-3-Methoxy-4-(methylamino)pyrrolidin-1-yl]-4-oxo-1-(1,3-thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChemSpider | |
| UNII | |
| |
| |
| Properties | |
| C18H19N5O4S | |
| Molar mass | 401.44 g·mol−1 |
| Density | 1.5±0.1 g/cm3 |
| Boiling point | 652,0±65,0 °C a 760 mmHg |
| Pharmacology | |
| L01XX53 (WHO) | |
| Hazards | |
| Flash point | 348.1±34.3 °C |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Vosaroxin (AG-7352,SPC-595,SNS 595,voreloxin) is atopoisomerase IIinhibitor causing site-selectiveDNA damage. It is under phase III clinical trial investigation foracute myelogenous leukemia (AML) andovarian cancer sponsored by Sunesis.[1]
Vosaroxin is anaphthyridineanalog of the anticancerquinolone derivatives (AQDs), a class of compounds that has not been used previously for the treatment of cancer. Topoisomerase II enzymes are essential for the survival ofeukaryotic cells. Vosaroxin hinders the reunion of topoisomerase II-induced double-strand breaks at selective sites inDNA, resulting inG2 arrest and cell death byapoptosis.[2]
Vosaroxin has been investigated primarily for the treatment of relapsed or refractory acute myeloid leukemia (AML). Phase I/II studies suggested antileukemic activity and manageable toxicity, and the phase III VALOR trial evaluated vosaroxin plus cytarabine versus placebo plus cytarabine in adults with relapsed/refractory AML.[3]
In the VALOR study, vosaroxin combined with cytarabine did not significantly improve overall survival in the full study population compared with placebo plus cytarabine. However, pre-specified subgroup analyses (such as patients aged ≥60 years or those with early relapse) showed trends toward improved outcomes, including higher complete remission rates.[4]
Phase I pharmacokinetic studies demonstrated linear pharmacokinetics across the investigated dose range (9–90 mg/m2). Vosaroxin shows a mean terminal half-life of approximately 24–25 hours, predominantly non-renal clearance, and a volume of distribution consistent with extensive tissue penetration. Co-administration with cytarabine does not significantly alter vosaroxin pharmacokinetics.[5]
The most common adverse events reported include myelosuppression (neutropenia, thrombocytopenia, and anemia) and infections or fever associated with neutropenia. In combination studies with cytarabine, higher rates of febrile neutropenia, mucositis, and stomatitis were observed compared with cytarabine alone. Severe non-hematologic toxicities were relatively uncommon, and clinically meaningful QT prolongation was rare in published data.[6]
Vosaroxin (also known as voreloxin, AG-7352, and SNS-595) is a small-molecule anticancer agent with the molecular formula C18H19N5O4S. It is a quinolone-derived naphthyridine analog structurally distinct from anthracyclines, but produces double-strand DNA breaks through topoisomerase II inhibition. Key identifiers include PubChem CID 9952884 and InChIKey XZAFZXJXZHRNAQ-STQMWFEESA-N.[7]
Vosaroxin was developed by Sunesis Pharmaceuticals (initially known as voreloxin/SNS-595). The clinical development program included multiple phase I and II studies and culminated in the phase III VALOR trial in relapsed/refractory AML. Although signals of efficacy were observed in specific patient subgroups, results from the overall study population did not lead to regulatory approval, and ongoing interest has focused on biomarker-defined subsets.[8]
Preclinical studies and reviews suggest potential activity of vosaroxin in models resistant to anthracyclines, partly due to differences in P-glycoprotein efflux and DNA damage mechanisms. Investigations continue into biomarkers of response, such as DNA damage–repair pathways, and whether specific AML subgroups may benefit in future studies.[9]
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