ADAT3 Inhibitors

ADAT3 inhibitors encompass a range of compounds that indirectly reduce the functional activity of ADAT3 by influencing the availability and state of its tRNA substrates, rather than directly inhibiting the enzyme itself. These compounds typically disrupt nucleotide metabolism or RNA processing pathways, leading to a reduction in the pool of tRNA substrates or alterations in the tRNA modification patterns that are essential for ADAT3 activity. For example, inhibitors like 5-Iodotubercidin and hydroxyurea reduce the availability of nucleotides necessary for proper tRNA synthesis and modification, thereby indirectly inhibiting the action of ADAT3. Compounds such as 2'-Deoxyadenosine and puromycin may compete with or mimic tRNA components, potentially preventing ADAT3 from accessing its normal substrate.

The indirect inhibition mechanisms also extend to compounds that affect DNA and RNA methyltransferase activities, such as decitabine and azacitidine, which can lead to changes in the RNA modification landscape, thereby indirectly affecting ADAT3's function in tRNA deamination. Other nucleoside analogs like cladribine and ribavirin disrupt the balance of nucleotide pools, which is crucial for the maintenance of tRNA substrate levels and, consequently, for the deamination reactions mediated by ADAT3. Methotrexate and clofarabine demonstrate the broader impact of nucleotide synthesis inhibition on the availability of tRNA substrates for enzymes like ADAT3, highlighting the interconnectedness of metabolic pathways and the indirect mechanisms through which ADAT3 activity can be modulated.