Gemcitabine (2',2'-difluorodeoxycitidine) is a difluorinated nucleoside analog. It is delivered as a prodrug that requires intracellular transport and phosphorylation to exert its cytotoxic effects and acts specifically during S-phase of the cell cycle.
This diagram shows the action of gemcitabine on a generic cancer cell. The diphosphate form is a potent inhibitor of ribonucleotide reductase (coded for by the genes RRM1, RRM2 and RRM2B) leading to perturbations in the deoxynucleotide pools, while the active triphosphate form is incorporated into DNA, resulting in interference with DNA chain elongation and disruption of cell growth.
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
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Entities in the Pathway
Drugs/Drug Classes (1)
Relationships in the Pathway
|Arrow From||Arrow To||Controllers||PMID|
|RRM1, RRM2, RRM2B||RRM1, RRM2, RRM2B||gemcitabine|
|NDPs||dNDPs||RRM1, RRM2, RRM2B|
|gemcitabine||gemcitabine||SLC28A1, SLC28A3, SLC29A1||10547395|
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