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Repurposing FDA Drug Compounds against Breast Cancer by Targeting EGFR/HER2
Repurposing studies have identified several FDA-approved compounds as potential inhibitors of the intracellular domain of epidermal growth factor receptor 1 (EGFR) and human epidermal receptor 2 (HER2). EGFR and HER2 represent important targets for the design of new drugs against different types of...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401258/ https://www.ncbi.nlm.nih.gov/pubmed/34451888 http://dx.doi.org/10.3390/ph14080791 |
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author | Balbuena-Rebolledo, Irving Padilla-Martínez, Itzia Irene Rosales-Hernández, Martha Cecilia Bello, Martiniano |
author_facet | Balbuena-Rebolledo, Irving Padilla-Martínez, Itzia Irene Rosales-Hernández, Martha Cecilia Bello, Martiniano |
author_sort | Balbuena-Rebolledo, Irving |
collection | PubMed |
description | Repurposing studies have identified several FDA-approved compounds as potential inhibitors of the intracellular domain of epidermal growth factor receptor 1 (EGFR) and human epidermal receptor 2 (HER2). EGFR and HER2 represent important targets for the design of new drugs against different types of cancer, and recently, differences in affinity depending on active or inactive states of EGFR or HER2 have been identified. In this study, we first identified FDA-approved compounds with similar structures in the DrugBank to lapatinib and gefitinib, two known inhibitors of EGFR and HER2. The selected compounds were submitted to docking and molecular dynamics MD simulations with the molecular mechanics generalized Born surface area approach to discover the conformational and thermodynamic basis for the recognition of these compounds on EGFR and HER2. These theoretical studies showed that compounds reached the ligand-binding site of EGFR and HER2, and some of the repurposed compounds did not interact with residues involved in drug resistance. An in vitro assay performed on two different breast cancer cell lines, MCF-7, and MDA-MB-23, showed growth inhibitory activity for these repurposed compounds on tumorigenic cells at micromolar concentrations. These repurposed compounds open up the possibility of generating new anticancer treatments by targeting HER2 and EGFR. |
format | Online Article Text |
id | pubmed-8401258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84012582021-08-29 Repurposing FDA Drug Compounds against Breast Cancer by Targeting EGFR/HER2 Balbuena-Rebolledo, Irving Padilla-Martínez, Itzia Irene Rosales-Hernández, Martha Cecilia Bello, Martiniano Pharmaceuticals (Basel) Article Repurposing studies have identified several FDA-approved compounds as potential inhibitors of the intracellular domain of epidermal growth factor receptor 1 (EGFR) and human epidermal receptor 2 (HER2). EGFR and HER2 represent important targets for the design of new drugs against different types of cancer, and recently, differences in affinity depending on active or inactive states of EGFR or HER2 have been identified. In this study, we first identified FDA-approved compounds with similar structures in the DrugBank to lapatinib and gefitinib, two known inhibitors of EGFR and HER2. The selected compounds were submitted to docking and molecular dynamics MD simulations with the molecular mechanics generalized Born surface area approach to discover the conformational and thermodynamic basis for the recognition of these compounds on EGFR and HER2. These theoretical studies showed that compounds reached the ligand-binding site of EGFR and HER2, and some of the repurposed compounds did not interact with residues involved in drug resistance. An in vitro assay performed on two different breast cancer cell lines, MCF-7, and MDA-MB-23, showed growth inhibitory activity for these repurposed compounds on tumorigenic cells at micromolar concentrations. These repurposed compounds open up the possibility of generating new anticancer treatments by targeting HER2 and EGFR. MDPI 2021-08-12 /pmc/articles/PMC8401258/ /pubmed/34451888 http://dx.doi.org/10.3390/ph14080791 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Balbuena-Rebolledo, Irving Padilla-Martínez, Itzia Irene Rosales-Hernández, Martha Cecilia Bello, Martiniano Repurposing FDA Drug Compounds against Breast Cancer by Targeting EGFR/HER2 |
title | Repurposing FDA Drug Compounds against Breast Cancer by Targeting EGFR/HER2 |
title_full | Repurposing FDA Drug Compounds against Breast Cancer by Targeting EGFR/HER2 |
title_fullStr | Repurposing FDA Drug Compounds against Breast Cancer by Targeting EGFR/HER2 |
title_full_unstemmed | Repurposing FDA Drug Compounds against Breast Cancer by Targeting EGFR/HER2 |
title_short | Repurposing FDA Drug Compounds against Breast Cancer by Targeting EGFR/HER2 |
title_sort | repurposing fda drug compounds against breast cancer by targeting egfr/her2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401258/ https://www.ncbi.nlm.nih.gov/pubmed/34451888 http://dx.doi.org/10.3390/ph14080791 |
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