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Multi-Targeted Histone Deacetylase Inhibitors in Cancer Therapy

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The heterogeneous nature of cancer requires a comprehensive approach for attacking the multiple mechanisms underlying the initiation and progression of cancers. Histone deacetylase inhibitors (HDACi) have emerged as a new class of anticancer agents, targeting the biological processes including cell cycle, apoptosis and differentiation. Studies have revealed that HDACi are synergistic with diverse classes of anticancer therapies including targeted therapeutics and conventional anticancer agents. Extensive medicinal chemistry efforts have yielded a wide range of chemical structures, indicative of the structural flexibility of HDACi. These findings have supported a strategy to generate multi-targeted HDACi by combining structural features from HDACi and other anticancer agents. HDACi can also be connected to a motif that allows for a selective delivery. Highlighting current examples, this brief review focuses on the rational design of multi-targeted inhibitors based on the examination and manipulation of chemical structures.

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Keywords: Cancer therapy; Chronic myelogenous leukemia; Drug discovery; Drug resistance; Dual inhibitor; Histone deacetylase; Histone deacetylase inhibitors; Inosine monophosphate dehydrogenase; Multi-targeted inhibitor; Protein kinase

Document Type: Research Article

Publication date: 2012-02-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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