NUDT12 Inhibitors

Inhibitors of NUDT12 function by impacting the cellular availability of its substrates and intermediates involved in nucleotide metabolism. For instance, certain compounds that inhibit the activity of xanthine oxidase or dihydrofolate reductase significantly reduce the cellular concentration of purine nucleotides. Since NUDT12 requires these purine nucleotides as substrates to function, its activity is indirectly diminished. Similarly, analogs and antagonists of nucleotides that impede nucleic acid synthesis or repair decrease the pool of nucleotides necessary for NUDT12 activity, leading to functional inhibition. Agents that specifically target enzymes like inosine monophosphate dehydrogenase or ribonucleotide reductase also lead to a depletion of guanine and deoxyribonucleotide triphosphates, respectively, which are crucial for the catalytic action of NUDT12. Further inhibitory effects on NUDT12 are observed when compounds interfere with the de novo synthesis of purine and pyrimidine nucleotides. By mimicking the natural substrates of NUDT12, certain inhibitors can be incorporated into DNA strands, resulting in a reduction of available substrates for NUDT12, thus indirectly impairing its function. Additionally, inhibitors that act on adenosine deaminase lead to an accumulation of specific nucleotides that are not only toxic to cells but could also affect the catalytic efficiency of NUDT12.