NVX-412, a new oncology drug candidate, induces S-phase arrest and DNA damage in cancer cells in a p53-independent manner.

Abstract

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.

• Authors: Alexandra Hebar, Barbara C Rütgen, Edgar Selzer
• Journal: PloS one (PLoS One) Vol. 7 Issue 9 Pg. e45015 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23028738 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• Hydrazines
• Quinoxalines
• Tumor Suppressor Protein p53
• pyrazine-2-carboxylic acid N'- (7-fluoropyrrolo(1,2-a)quinoxalin-4-yl)-hydrazide

Topics

• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• Biomarkers, Tumor (metabolism)
• Cell Line, Tumor
• Cell Shape (drug effects)
• Cell Size (drug effects)
• DNA Damage
• DNA Replication (drug effects)
• Drug Screening Assays, Antitumor
• Humans
• 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 Suppressor Protein p53 (metabolism)