Figure 13.

A general scheme for metabolism of nucleosides using F₂C as an example (64). F₂C and ClF therapeutics require cellular uptake and phosphorylation to the appropriate state recognized by target enzymes. The former is mediated by nucleoside transporters ENT1, ENT2, and CNT [1]. Once inside the cell, both F₂C and ClF are phosphorylated to the monophosphate by deoxycytidine kinase [3] and subsequently to the di and triphosphates by cellular kinases [4 and 6]. Deoxycytidine kinase has unusual specificity in that it phosphorylates both pyrimidines and purines. The concentrations of the monophosphates are in general > than the triphosphates ≫ than the diphosphates, are cell type distinct, and influence therapeutic outcomes. [5] is RNR, [7] is DNA polymerase, and [2] is cytidine deaminase.