Gemcitabine is a nucleoside analog of deoxycytidine used as chemotherapy to treat patients with various types of cancer. After passage through the cell membrane via nucleoside transporters, gemcitabine undergoes complex intracellular conversion to gemcitabine diphosphate (dFdCDP) and triphosphate (dFdCTP). dFdCTP inhibits DNA polymerase by competing with deoxycytidine triphosphate (dCTP). dFdCDP inhibits ribonucleoside reductase and DNA synthesis by causing depletion of deoxyribonucleotide pools, and thus potentiating the effects of dFdCTP. Gemcitabine can be inactivated to 2,2'-difluorodeoxyuridine, mainly by deoxycytidine deaminase. Also, 5'-nucleotidase catalyses the conversion of nucleotides to nucleosides and inhibits nucleoside kinases.
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