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Cancer Biol Ther. 2004 Nov;3(11):1062-8. Epub 2004 Nov 12.

Mechanism of inhibition of DNA methyltransferases by cytidine analogs in cancer therapy.

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School of Engineering and Science, International University Bremen, Bremen 28759, Germany.


Hypermethylation of tumor suppressor genes caused by aberrant activity of DNA methyltransferases is an important mechanism that contributes to cancer. The reaction mechanism of DNA methyltransferases, which includes formation of a covalent intermediate between the enzyme and the target base, is the basis of the success of several anti-cancer drugs that are targeted against DNA methylation. These include 5-fluoro-2'-deoxycytidine, 5-aza-2'-deoxycytidine (Decitabine) and 2-H pyrimidinone-1-beta-D(2'-deoxyriboside) (Zebularine). This review provides an insight to how the chemistry of DNA methylation is involved in the performance of these drugs targeted against it.

[Indexed for MEDLINE]

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