Abstract Gemcitabine (2 I, 2 I-difluorodeoxycytidine, dFdC) is a nucleoside analogue of
deoxycytidine in which two fluorine atoms have been inserted into the deoxyribofuranosyl
ring. Once inside the cell gemcitabine is rapidly phosphorylated by deoxycytidine kinase, the
rate-limiting enzyme for the formation of the active metabolites gemcitabine diphosphate
(dFdCDP) and gemcitabine triphosphate (dFdCTP). Gemcitabine diphosphate inhibits
ribonucleotide reductase, which is responsible for producing the deoxynucleotides required …