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Gemcitabine, a pyrimidine nucleoside analog, inhibits DNA synthesis in proliferating cells by two main mechanisms: it inhibits ribonucleotide reductase (via its diphosphate metabolite), lowering the pool of deoxynucleotides required for DNA replication, and it is incorporated into DNA (as its triphosphate metabolite), leading to masked chain termination and apoptosis. This mechanism is highly effective in cancer therapy, targeting rapidly dividing tumor cells, but can also affect healthy proliferating cells, leading to adverse effects such as myelosuppression and, in rare cases, liver toxicity
Inhibition of ribonucleotide reductase, depleting deoxynucleotide pools needed for DNA synthesis (via gemcitabine diphosphate); Incorporation of gemcitabine triphosphate into DNA, causing masked chain termination and apoptosis; Self-potentiation: lowering dCTP levels, enhancing gemcitabine incorporation
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See how Gosset can support your research on Ribonucleotide reductase; DNA polymerase (RRM1 (for ribonucleotide reductase), null for DNA synthesis inhibition as a whole).