Ho Ho

HO Trimidox

HO Trimidox

3.3. Substrate analogs as RNR inhibitors

RNR substrate analogs are normally modified at C-2', which is the position that undergoes reduction in the natural substrate. Many of these compounds bind covalently to the enzyme.

Tezacitabine (fluoromethylenedeoxycytidine, FMdC) is a nucleoside prodrug that shows a dual mechanism of action. Following intracellular phosphorylation, the tezacitabine diphosphate irreversibly inhibits RNR, while the tezacitabine triphosphate can be incorporated into DNA during replication or repair, resulting in DNA chain termination.9 After initially promising clinical data, analysis of the data from a Phase II trial in patients with gastroesophageal cancer prompted the decision to discontinue further development of tezacitabine.

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