17 Troxacitabine

Generally the drugs act not through inhibition of a single enzyme, but through interaction as substrate or inhibitor of several enzymes; the primary mechanism is shown in Table 5. For example, decitabine (14) competes with deoxycytidine for conversion to the monophosphate by deoxycytidine kinase.33 In doing so, intracellular levels of cytidine monophosphate are decreased. In addition, decitabine monophosphate is converted via its diphosphate to the triphosphate, decitabine triphosphate, which is then incorporated into DNA. It acts as a cytosine residue until it covalently inhibits DNA methyltransferase. Hypermethylation silences signal transduction pathways in tumor cells, and thus decitabine inhibits tumor cell proliferation.

Table 5 Summary of mechanism of action and active form of drug for selected nucleoside analogs

Clinical agent

Analog of which nucleoside?

Mechanism of action

Active form of drug

0 0

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