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Anti-breast cancer activity of selected 1,3,5-triazines via modulation of EGFR-TK
The present study investigated the effect of certain 1,3,5-triazine derivatives on epidermal growth factor receptor-tyrosine kinase (EGFR-TK). The results suggested that 1,3,5-triazine derivatives exhibited optimal drug likeness via molinspiration and proved to be effective drug candidates as potent...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172377/ https://www.ncbi.nlm.nih.gov/pubmed/30152850 http://dx.doi.org/10.3892/mmr.2018.9426 |
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author | Yan, Weixin Zhao, Yiyang He, Jianrong |
author_facet | Yan, Weixin Zhao, Yiyang He, Jianrong |
author_sort | Yan, Weixin |
collection | PubMed |
description | The present study investigated the effect of certain 1,3,5-triazine derivatives on epidermal growth factor receptor-tyrosine kinase (EGFR-TK). The results suggested that 1,3,5-triazine derivatives exhibited optimal drug likeness via molinspiration and proved to be effective drug candidates as potential anticancer agents. The molecules were demonstrated to interact with key catalytic residues of EGFR, including Asn818, Lys721, Leu694, Val702 and Met742 as demonstrated in molecular docking experiments. Compound 1d was demonstrated to be the most potent analogue with an inhibitory constant of 0.44 nM, against EGFR-TK in in-vitro enzyme inhibition assay. Compound 1d was further evaluated for its effect on the cellular viability of three breast cancer cell lines, including highly metastatic MDAMB231, human epidermal growth factor receptor 2-positive BT474 and estrogen receptorpositive MCF7 cells, using an MTT assay and apoptosis analysis. Western blot analysis was performed to examine the levels of β-catenin in the control and treated cells. Based on the findings of the current study, the chemical 1,3,5-triazine series are potential novel inhibitors of EGFR-TK and β-catenin signaling, and may be potent anti-breast cancer agents. |
format | Online Article Text |
id | pubmed-6172377 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-61723772018-10-19 Anti-breast cancer activity of selected 1,3,5-triazines via modulation of EGFR-TK Yan, Weixin Zhao, Yiyang He, Jianrong Mol Med Rep Articles The present study investigated the effect of certain 1,3,5-triazine derivatives on epidermal growth factor receptor-tyrosine kinase (EGFR-TK). The results suggested that 1,3,5-triazine derivatives exhibited optimal drug likeness via molinspiration and proved to be effective drug candidates as potential anticancer agents. The molecules were demonstrated to interact with key catalytic residues of EGFR, including Asn818, Lys721, Leu694, Val702 and Met742 as demonstrated in molecular docking experiments. Compound 1d was demonstrated to be the most potent analogue with an inhibitory constant of 0.44 nM, against EGFR-TK in in-vitro enzyme inhibition assay. Compound 1d was further evaluated for its effect on the cellular viability of three breast cancer cell lines, including highly metastatic MDAMB231, human epidermal growth factor receptor 2-positive BT474 and estrogen receptorpositive MCF7 cells, using an MTT assay and apoptosis analysis. Western blot analysis was performed to examine the levels of β-catenin in the control and treated cells. Based on the findings of the current study, the chemical 1,3,5-triazine series are potential novel inhibitors of EGFR-TK and β-catenin signaling, and may be potent anti-breast cancer agents. D.A. Spandidos 2018-11 2018-08-24 /pmc/articles/PMC6172377/ /pubmed/30152850 http://dx.doi.org/10.3892/mmr.2018.9426 Text en Copyright: © Yan et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Yan, Weixin Zhao, Yiyang He, Jianrong Anti-breast cancer activity of selected 1,3,5-triazines via modulation of EGFR-TK |
title | Anti-breast cancer activity of selected 1,3,5-triazines via modulation of EGFR-TK |
title_full | Anti-breast cancer activity of selected 1,3,5-triazines via modulation of EGFR-TK |
title_fullStr | Anti-breast cancer activity of selected 1,3,5-triazines via modulation of EGFR-TK |
title_full_unstemmed | Anti-breast cancer activity of selected 1,3,5-triazines via modulation of EGFR-TK |
title_short | Anti-breast cancer activity of selected 1,3,5-triazines via modulation of EGFR-TK |
title_sort | anti-breast cancer activity of selected 1,3,5-triazines via modulation of egfr-tk |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172377/ https://www.ncbi.nlm.nih.gov/pubmed/30152850 http://dx.doi.org/10.3892/mmr.2018.9426 |
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