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NVX-412, a New Oncology Drug Candidate, Induces S-Phase Arrest and DNA Damage in Cancer Cells in a p53-Independent Manner

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 NV...

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Detalles Bibliográficos
Autores principales: Hebar, Alexandra, Rütgen, Barbara C., Selzer, Edgar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441706/
https://www.ncbi.nlm.nih.gov/pubmed/23028738
http://dx.doi.org/10.1371/journal.pone.0045015
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author Hebar, Alexandra
Rütgen, Barbara C.
Selzer, Edgar
author_facet Hebar, Alexandra
Rütgen, Barbara C.
Selzer, Edgar
author_sort Hebar, Alexandra
collection PubMed
description 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.
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spelling pubmed-34417062012-10-01 NVX-412, a New Oncology Drug Candidate, Induces S-Phase Arrest and DNA Damage in Cancer Cells in a p53-Independent Manner Hebar, Alexandra Rütgen, Barbara C. Selzer, Edgar PLoS One Research Article 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. Public Library of Science 2012-09-13 /pmc/articles/PMC3441706/ /pubmed/23028738 http://dx.doi.org/10.1371/journal.pone.0045015 Text en © 2012 Hebar et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hebar, Alexandra
Rütgen, Barbara C.
Selzer, Edgar
NVX-412, a New Oncology Drug Candidate, Induces S-Phase Arrest and DNA Damage in Cancer Cells in a p53-Independent Manner
title NVX-412, a New Oncology Drug Candidate, Induces S-Phase Arrest and DNA Damage in Cancer Cells in a p53-Independent Manner
title_full NVX-412, a New Oncology Drug Candidate, Induces S-Phase Arrest and DNA Damage in Cancer Cells in a p53-Independent Manner
title_fullStr NVX-412, a New Oncology Drug Candidate, Induces S-Phase Arrest and DNA Damage in Cancer Cells in a p53-Independent Manner
title_full_unstemmed NVX-412, a New Oncology Drug Candidate, Induces S-Phase Arrest and DNA Damage in Cancer Cells in a p53-Independent Manner
title_short NVX-412, a New Oncology Drug Candidate, Induces S-Phase Arrest and DNA Damage in Cancer Cells in a p53-Independent Manner
title_sort nvx-412, a new oncology drug candidate, induces s-phase arrest and dna damage in cancer cells in a p53-independent manner
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441706/
https://www.ncbi.nlm.nih.gov/pubmed/23028738
http://dx.doi.org/10.1371/journal.pone.0045015
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