Gemcitabine is a nucleoside analog that acts by multiple mechanisms. Incorporation of the triphosphate and subsequent inhibition of DNA replication and repair appears to be the major mode of action. Ribonucleotide reductase is inhibited by gemcitabine diphosphate, an activity that leads to metabolic self-potentiating effects.
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Plunkett et al. (1997) studied this question.
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