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Anticancer Drug Discovery Targeting DNA Hypermethylation

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DNA methyltransferases (DNMTs) are important regulators of gene transcription and their roles in carcinogenesis have been a topic of considerable interest in the last few years. Diverse classes of chemical compounds including nucleotide analogues, adenosine analogues, aminobenzoic derivatives, polyphenols, hydrazines, phthalides, disulfides and antisenses are being discovered and evaluated as DNMT inhibitors targeting DNA hypermethylation. Among them, 5-Azacytidine 5 and Decitabine 6 were launched recently. Several other compounds are under clinical trials. Some of these compounds were discovered from structure-based drug design. These compounds exert their DNA methylation inhibitory by different mechanisms. This review will present a brief account of various DNA methyltransferases and their biological functions, with focus on actuality of design and synthesis of various inhibitors of DNA hypermethylation as anticancer drugs.
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Keywords: Anticancer drugs; DNA hypermethylation Inhibitors; DNA methylation; Drug discovery; Epigenetics

Document Type: Research Article

Affiliations: Institute of Molecular Design and Drug Discovery, School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan, P.R. China.

Publication date: 2008-06-01

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