Document Detail

NVX-412, a new oncology drug candidate, induces S-phase arrest and DNA damage in cancer cells in a p53-independent manner.
MedLine Citation:
PMID:  23028738     Owner:  NLM     Status:  MEDLINE    
The new molecular entity quinoxalinhydrazide derivative NVX-412 was identified as a promising drug candidate for the treatment of various cancer types due to its strong cytotoxic activity and relative specificity. Here, we provide first data about the mechanisms of action of NVX-412. We show that NVX-412 exerts its anti-neoplastic activity in a p53-independent manner and induces S-phase arrest and DNA damage as assessed by γH2AX staining. We suggest a bi-modal (dose-dependent) mode of action of NVX-412, being primarily cytostatic at lower and predominantly cytotoxic at higher concentrations. Based on the broad and consistent anti-neoplastic activity observed, NVX-412 holds promise as an effective drug candidate for the treatment of various cancer types, especially for hematological malignancies with highly unmet medical need.
Alexandra Hebar; Barbara C Rütgen; Edgar Selzer
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Publication Detail:
Type:  Journal Article     Date:  2012-09-13
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-02-26     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e45015     Citation Subset:  IM    
Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria.
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MeSH Terms
Antineoplastic Agents / chemistry,  pharmacology*,  therapeutic use*
Cell Line, Tumor
Cell Shape / drug effects
Cell Size / drug effects
DNA Damage*
DNA Replication / drug effects
Drug Screening Assays, Antitumor
Hydrazines / chemistry,  pharmacology*,  therapeutic use*
Inhibitory Concentration 50
Neoplasms / drug therapy*,  pathology*
Phosphorylation / drug effects
Quinoxalines / chemistry,  pharmacology*,  therapeutic use*
S Phase Cell Cycle Checkpoints / drug effects*
Tumor Markers, Biological / metabolism
Tumor Suppressor Protein p53 / metabolism
Reg. No./Substance:
0/Antineoplastic Agents; 0/Hydrazines; 0/Quinoxalines; 0/Tumor Markers, Biological; 0/Tumor Suppressor Protein p53; 0/pyrazine-2-carboxylic acid N'- (7-fluoropyrrolo(1,2-a)quinoxalin-4-yl)-hydrazide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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