ATP11B Inhibitors

Chemical inhibitors of ATP11B can impede the protein's function through a variety of mechanisms, all converging on the inhibition of the ATPase activity that is central to its function. Ouabain and digoxin, for instance, exert their inhibitory effect by specifically targeting Na+/K+-ATPase, which can in turn indirectly affect ATP11B due to the shared dependency on ion gradients that are crucial for maintaining ATPase activity. The proper function of ATP11B relies on the electrochemical potential across cellular membranes, and the disruption of these ion gradients by ouabain and digoxin can inhibit its activity. Thapsigargin serves as an inhibitor of the SERCA pumps, leading to altered calcium homeostasis; this change can adversely affect ATP11B if the protein's function is regulated by calcium signaling. Brefeldin A disrupts protein trafficking within the Golgi apparatus, which can impede the proper localization and function of ATP11B, as its operation may rely on correct cellular trafficking to perform its role.

Further, monensin, as a sodium ionophore, disrupts ionic gradients, which are fundamental for ATP11B's ion-dependent ATPase activity. This disruption can lead to functional inhibition of ATP11B. Vanadate acts as a phosphate analog and can destabilize ATP11B's phosphorylation cycle, inhibiting its activity by disrupting the binding and hydrolysis of ATP. Oligomycin, while traditionally an inhibitor of F-type ATPases, can indirectly affect ATP11B by disrupting the proton gradients, which are potentially vital for ATP11B's energy utilization. Azide interferes with ATPases by impeding the phosphorylation process, which is essential for ATP hydrolysis by ATP11B. Verapamil, as a calcium channel blocker, can indirectly inhibit ATP11B if the protein requires finely tuned calcium levels for its function. Beryllium fluoride competes with ATP at ATP11B's active site, potentially inhibiting the necessary phosphorylation for ATP hydrolysis. Catechin, known to inhibit ATPases, can bind to ATP11B, thereby interfering with ATP binding or hydrolysis and inhibiting the protein's function. Lastly, N-Ethylmaleimide, which alkylates thiol groups, can modify cysteine residues and inhibit ATPases, potentially affecting the catalytic function of ATP11B by altering its active site.