ASB-12 Inhibitors

ASB-12 inhibitors work by influencing the ubiquitin-proteasome system and related protein degradation pathways. This is because ASB-12 is an E3 ubiquitin ligase, and its main function is to mark proteins for degradation via the proteasome. Bortezomib, MG-132, Epoxomicin, and Lactacystin are all proteasome inhibitors. They inhibit the proteasome, preventing the degradation of ubiquitinated proteins and thereby disrupting the balance of protein turnover regulated by ASB-12. On the other hand, MLN4924, a NEDD8-activating enzyme inhibitor, hinders the modification of cullin proteins, which are part of the Cullin-RING E3 ubiquitin ligases that ASB-12 is a member of, thus leading to decreased activity of ASB-12.

Certain inhibitors target the ubiquitination process itself to indirectly affect the function of ASB-12. PYR-41, an irreversible inhibitor of ubiquitin-activating enzyme E1, hampers the initiation of ubiquitination. This results in ASB-12 being unable to mark proteins for degradation, as ubiquitination is an essential initiation step. PR-619 is a broad-spectrum deubiquitinase inhibitor that obstructs the removal of ubiquitin from proteins, disrupting the balance of ubiquitination and deubiquitination. This can inhibit ASB-12's function, as deubiquitination is a necessary step in the degradation of proteins marked by ASB-12. Other inhibitors like Chloroquine, Eeyarestatin I, Auranofin, and Leupeptin influence various processes like lysosomal function, endoplasmic reticulum-associated degradation, oxidative stress, and protease activity respectively to indirectly affect the function of ASB-12.