NUDT15 Activators

NUDT15 Activators refer to substances that can modulate the activity of the NUDT15 enzyme. Most of these are purine or nucleoside analogs that interfere with DNA and RNA synthesis, or nucleotide metabolism. By getting incorporated into DNA or RNA, or by affecting nucleotide synthesis, these chemicals introduce changes in the pool of substrates that NUDT15 interacts with, and thus indirectly modulate its activity. For instance, 6-thioguanine and thioguanine are purine analogs that get incorporated into DNA and RNA, affecting their synthesis and function. This changes the substrates that NUDT15 interacts with, influencing its activity. 6-Mercaptopurine, azathioprine, and fludarabine also function in a similar way, by inhibiting nucleotide synthesis and altering the nucleotide pool.

On the other hand, some chemicals like pentostatin and forodesine inhibit enzymes involved in nucleotide metabolism, leading to an increase in certain types of nucleotides in cells. This change in the intracellular nucleotide pool can also indirectly affect NUDT15 activity. For example, pentostatin is an adenosine deaminase inhibitor that can increase the concentration of dATP in cells, which serves as a substrate for NUDT15. A similar effect can be observed with forodesine, a purine nucleoside phosphorylase inhibitor.