Figure 3.

Overview on the pharmacodynamics of nucleobase/nucleoside analogues. Nucleobase (NbA, light yellow) and nucleoside analogues (NsA, light green) are metabolised intracellularly to produce their active metabolites (NsA, light red), be it the mono- (P), di- (PP) and triphosphate (PPP) species. These can inhibit key enzymes in DNA precursor metabolism, such as thymidylate synthase (TS) or ribonucleotide reductase (RNR), or be incorporated into nucleic acids. Here, these analogues can perturb DNA synthesis by DNA polymerases (DNA Pol) at the extension step, or the resultant genomic lesions can inhibit other enzymes, such as DNA methyltransferases (DNMTs), or lead to futile DNA repair cycles.