NUDT3 Inhibitors

Chemical inhibitors of NUDT3 can impede the activity of the protein through various mechanisms that focus on the inhibition of its ATPase and hydrolase functions. Suramin, for instance, is known to inhibit the activity of a range of enzymes with nucleotidase activity and could directly block the active site of NUDT3, preventing it from engaging in its normal enzymatic processes. Similarly, TNP-ATP acts as a competitive inhibitor and can bind to the ATP-binding site of NUDT3, thereby blocking ATP from being hydrolyzed, which is a central aspect of NUDT3's function. ARL-67156, another inhibitor, prevents the hydrolysis of ATP by NUDT3, thus directly reducing its ability to regulate ADP-ribose levels, which is part of the protein's role. Sodium polyoxotungstate and periodate-oxidized ATP can both inhibit the ATPase activity of NUDT3, with the former inhibiting a range of ATPases and the latter binding to the ATP binding site but not serving as a substrate for hydrolysis. Continuing with the theme of targeting the ATPase activity of NUDT3, β,γ-Methyleneadenosine 5'-triphosphate presents itself as a non-hydrolyzable analog of ATP, which competes with ATP at the active site of NUDT3, thus preventing the protein from performing its enzymatic activity. Reactive Blue 2 and NF449 both act as inhibitors of purinergic receptors but can extend their inhibitory action to NUDT3 by blocking the nucleotide binding site, directly inhibiting the protein's function. Oxidized ATP acts as an irreversible inhibitor by covalently binding to the active site of NUDT3, leading to a permanent inhibition of its ATPase activity. MRS2578 selectively inhibits P2Y purinergic receptors but can inhibit NUDT3 by blocking nucleotide binding. Lastly, PPADS, a non-selective purinergic receptor antagonist, can inhibit NUDT3 by preventing ATP from binding to the enzyme, thus directly inhibiting the activity of NUDT3 in its role as a nucleotide hydrolase.