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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...

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Detalles Bibliográficos
Autores principales: Zhang, Xuan, Su, Mingbo, Chen, Yi, Li, Jia, Lu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
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.
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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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