- freely available
The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors
AbstractOver 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.
Share & Cite This Article
Zhang, X.; Su, M.; Chen, Y.; Li, J.; Lu, W. The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors. Molecules 2013, 18, 6491-6503.View more citation formats
Zhang X, Su M, Chen Y, Li J, Lu W. The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors. Molecules. 2013; 18(6):6491-6503.Chicago/Turabian Style
Zhang, Xuan; Su, Mingbo; Chen, Yi; Li, Jia; Lu, Wei. 2013. "The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors." Molecules 18, no. 6: 6491-6503.
Notes: Multiple requests from the same IP address are counted as one view.