The effects of AZA/6-MP are mediated via the drug’s intracellular conversion to thiopurine nucleotide metabolites, which are incorporated into cellular nucleic acids, a process which leads to inhibition of de novo purine synthesis. As shown in Figure 1, AZA is rapidly converted to 6-MP via nonenzymatic processes, after which 6-MP may be catabo-lized to the inactive metabolite, 6-methylmercaptopurine (6-MMP), or anabolized to the active metabolites, 6-thioguanine nucleotides (6-TG) and 6-MMP ribonucleotides, via competing pathways. The methylation of 6-MP to 6-MMP ribonucleotides is catalyzed by thiopurine methyltransferase (TPMT). Continue reading