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Decitabine


Mechanism of action:

Decitabine is a deoxycytidine analog. Inside the cell, decitabine is phosphorylated by deoxycytidine kinase to form decitabine monophosphate, and is then further phosphorylated by other kinases into decitabine triphosphate. Decitabine triphosphate can replace cytosine and become incorporated into DNA. Once incorporated into DNA, decitabine causes DNA methyltransferase (DNMT) to form a covalent complex and become functionally inhibited. This suppresses methylation of newly synthesized DNA and promotes re-expression of abnormally silenced tumor suppressor genes.

Reference(s):

1. Appleton K et al. (2007). Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumors. J Clin Oncol. 


2. Wijermans PW et al. (2008). Efficacy of decitabine in the treatment of patients with chronic myelomonocytic leukemia (CMML). Leuk Res.

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