Cargando…
Pre-clinical evaluation of a novel class of anti-cancer agents, the Pyrrolo-1, 5-benzoxazepines
Microtubules are currently ranked one of the most validated targets for chemotherapy; with clinical use of microtubule targeting agents (MTAs) extending beyond half a century. Recent research has focused on the development of novel MTAs to combat drug resistance and drug associated toxicities. Of pa...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166549/ https://www.ncbi.nlm.nih.gov/pubmed/27994676 http://dx.doi.org/10.7150/jca.16616 |
_version_ | 1782483050743988224 |
---|---|
author | Greene, LM Butini, S Campiani, G Williams, DC Zisterer, DM |
author_facet | Greene, LM Butini, S Campiani, G Williams, DC Zisterer, DM |
author_sort | Greene, LM |
collection | PubMed |
description | Microtubules are currently ranked one of the most validated targets for chemotherapy; with clinical use of microtubule targeting agents (MTAs) extending beyond half a century. Recent research has focused on the development of novel MTAs to combat drug resistance and drug associated toxicities. Of particular interest are compounds structurally different to those currently used within the clinic. The pyrrolo-1, 5-benzoxazepines (PBOXs) are a structurally distinct novel group of anti-cancer agents, some of which target tubulin. Herein, we review the chemistry, mechanism of action, preclinical development of the PBOXs and comparisons with clinically relevant chemotherapeutics. The PBOXs induce a range of cellular responses including; cell cycle arrest, apoptosis, autophagy, anti-vascular and anti-angiogenic effects. The apoptotic potential of the PBOXs extends across a wide spectrum of cancer-derived cell lines, by targeting tubulin and multiple molecular pathways frequently deregulated in human cancers. Extensive experimental data suggest that combining the PBOXs with established chemotherapeutics or radiation is therapeutically advantageous. Pre-clinical highlights of the PBOXs include; cancer specificity and improved therapeutic efficacy as compared to some current first line therapeutics. |
format | Online Article Text |
id | pubmed-5166549 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-51665492016-12-19 Pre-clinical evaluation of a novel class of anti-cancer agents, the Pyrrolo-1, 5-benzoxazepines Greene, LM Butini, S Campiani, G Williams, DC Zisterer, DM J Cancer Review Microtubules are currently ranked one of the most validated targets for chemotherapy; with clinical use of microtubule targeting agents (MTAs) extending beyond half a century. Recent research has focused on the development of novel MTAs to combat drug resistance and drug associated toxicities. Of particular interest are compounds structurally different to those currently used within the clinic. The pyrrolo-1, 5-benzoxazepines (PBOXs) are a structurally distinct novel group of anti-cancer agents, some of which target tubulin. Herein, we review the chemistry, mechanism of action, preclinical development of the PBOXs and comparisons with clinically relevant chemotherapeutics. The PBOXs induce a range of cellular responses including; cell cycle arrest, apoptosis, autophagy, anti-vascular and anti-angiogenic effects. The apoptotic potential of the PBOXs extends across a wide spectrum of cancer-derived cell lines, by targeting tubulin and multiple molecular pathways frequently deregulated in human cancers. Extensive experimental data suggest that combining the PBOXs with established chemotherapeutics or radiation is therapeutically advantageous. Pre-clinical highlights of the PBOXs include; cancer specificity and improved therapeutic efficacy as compared to some current first line therapeutics. Ivyspring International Publisher 2016-12-04 /pmc/articles/PMC5166549/ /pubmed/27994676 http://dx.doi.org/10.7150/jca.16616 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. |
spellingShingle | Review Greene, LM Butini, S Campiani, G Williams, DC Zisterer, DM Pre-clinical evaluation of a novel class of anti-cancer agents, the Pyrrolo-1, 5-benzoxazepines |
title | Pre-clinical evaluation of a novel class of anti-cancer agents, the Pyrrolo-1, 5-benzoxazepines |
title_full | Pre-clinical evaluation of a novel class of anti-cancer agents, the Pyrrolo-1, 5-benzoxazepines |
title_fullStr | Pre-clinical evaluation of a novel class of anti-cancer agents, the Pyrrolo-1, 5-benzoxazepines |
title_full_unstemmed | Pre-clinical evaluation of a novel class of anti-cancer agents, the Pyrrolo-1, 5-benzoxazepines |
title_short | Pre-clinical evaluation of a novel class of anti-cancer agents, the Pyrrolo-1, 5-benzoxazepines |
title_sort | pre-clinical evaluation of a novel class of anti-cancer agents, the pyrrolo-1, 5-benzoxazepines |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166549/ https://www.ncbi.nlm.nih.gov/pubmed/27994676 http://dx.doi.org/10.7150/jca.16616 |
work_keys_str_mv | AT greenelm preclinicalevaluationofanovelclassofanticanceragentsthepyrrolo15benzoxazepines AT butinis preclinicalevaluationofanovelclassofanticanceragentsthepyrrolo15benzoxazepines AT campianig preclinicalevaluationofanovelclassofanticanceragentsthepyrrolo15benzoxazepines AT williamsdc preclinicalevaluationofanovelclassofanticanceragentsthepyrrolo15benzoxazepines AT zistererdm preclinicalevaluationofanovelclassofanticanceragentsthepyrrolo15benzoxazepines |