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The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors
Over the years, the development of targeted medicines has made significant achievements. As a typical example, receptor tyrosine kinases (RTK) inhibitors have become important chemotherapy drugs for a variety of cancers. However, the effectiveness of these agents is always hindered by poor response...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269723/ https://www.ncbi.nlm.nih.gov/pubmed/23736786 http://dx.doi.org/10.3390/molecules18066491 |
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author | Zhang, Xuan Su, Mingbo Chen, Yi Li, Jia Lu, Wei |
author_facet | Zhang, Xuan Su, Mingbo Chen, Yi Li, Jia Lu, Wei |
author_sort | Zhang, Xuan |
collection | PubMed |
description | Over the years, the development of targeted medicines has made significant achievements. As a typical example, receptor tyrosine kinases (RTK) inhibitors have become important chemotherapy drugs for a variety of cancers. However, the effectiveness of these agents is always hindered by poor response rates and acquired drug resistance. In order to overcome these limitations, several dual-targeted inhibitors with quinazoline core were designed and synthesized. Though these compounds can simultaneously inhibit histone deacetylases (HDAC) as well as RTK, the structure-activity relationship (SAR) is still not clear enough. To further explore this type of dual-targeted inhibitors, a new class of quinazoline derivatives were designed and synthesized. Their activity evaluations include in vitro inhibitory activity of HDAC, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). The SAR study indicated that the introduction of polar group such as hydroxamate on the 4-position of the quinazoline core is more likely to provide a potent HDACi/HER2i hybrid rather than HDACi/EGFRi molecule. |
format | Online Article Text |
id | pubmed-6269723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62697232018-12-17 The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors Zhang, Xuan Su, Mingbo Chen, Yi Li, Jia Lu, Wei Molecules Article Over the years, the development of targeted medicines has made significant achievements. As a typical example, receptor tyrosine kinases (RTK) inhibitors have become important chemotherapy drugs for a variety of cancers. However, the effectiveness of these agents is always hindered by poor response rates and acquired drug resistance. In order to overcome these limitations, several dual-targeted inhibitors with quinazoline core were designed and synthesized. Though these compounds can simultaneously inhibit histone deacetylases (HDAC) as well as RTK, the structure-activity relationship (SAR) is still not clear enough. To further explore this type of dual-targeted inhibitors, a new class of quinazoline derivatives were designed and synthesized. Their activity evaluations include in vitro inhibitory activity of HDAC, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). The SAR study indicated that the introduction of polar group such as hydroxamate on the 4-position of the quinazoline core is more likely to provide a potent HDACi/HER2i hybrid rather than HDACi/EGFRi molecule. MDPI 2013-06-03 /pmc/articles/PMC6269723/ /pubmed/23736786 http://dx.doi.org/10.3390/molecules18066491 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Zhang, Xuan Su, Mingbo Chen, Yi Li, Jia Lu, Wei The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors |
title | The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors |
title_full | The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors |
title_fullStr | The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors |
title_full_unstemmed | The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors |
title_short | The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors |
title_sort | design and synthesis of a new class of rtk/hdac dual-targeted inhibitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269723/ https://www.ncbi.nlm.nih.gov/pubmed/23736786 http://dx.doi.org/10.3390/molecules18066491 |
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