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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2013-06-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/18/6/6491 |
| _version_ | 1819090899085295616 |
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| author | Wei Lu Jia Li Xuan Zhang Yi Chen Mingbo Su |
| author_facet | Wei Lu Jia Li Xuan Zhang Yi Chen Mingbo Su |
| author_sort | Wei Lu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T22:31:09Z |
| format | Article |
| id | doaj.art-1931d88e67a04fde989bca8c31affee4 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-21T22:31:09Z |
| publishDate | 2013-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-1931d88e67a04fde989bca8c31affee42022-12-21T18:48:04ZengMDPI AGMolecules1420-30492013-06-011866491650310.3390/molecules18066491The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted InhibitorsWei LuJia LiXuan ZhangYi ChenMingbo SuOver 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.http://www.mdpi.com/1420-3049/18/6/6491receptor tyrosine kinaseshistone deacetylaseantitumorsynergistic effectdual inhibitor |
| spellingShingle | Wei Lu Jia Li Xuan Zhang Yi Chen Mingbo Su The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors Molecules receptor tyrosine kinases histone deacetylase antitumor synergistic effect dual inhibitor |
| 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 | receptor tyrosine kinases histone deacetylase antitumor synergistic effect dual inhibitor |
| url | http://www.mdpi.com/1420-3049/18/6/6491 |
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