ASB-3 Inhibitors

ASB-3 inhibitors work by influencing the ubiquitin-proteasome system and related protein degradation pathways. This is because ASB-3 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 disruptingthe balance that ASB-3 helps to maintain through marking proteins for destruction. The result is an accumulation of proteins that were marked by ASB-3, leading to its functional inhibition.

Other compounds disrupt the ubiquitin-proteasome system in different ways. PYR-41, for instance, inhibits the initiation of ubiquitination by targeting ubiquitin-activating enzyme E1, preventing ASB-3 from marking proteins for degradation. Compounds like MLN4924 target the NEDD8 pathway, which is involved in the modification of cullins, a crucial component of E3 ubiquitin ligases like ASB-3. Other inhibitors, such as PR-619, target the deubiquitination process, which is essential for the degradation of proteins marked by ASB-3. Eeyarestatin I targets the ER-associated degradation pathway, which, when inhibited, disrupts the balance between protein synthesis and degradation that ASB-3 is involved in. Chloroquine and Leupeptin inhibit lysosomal function and protease activity, respectively, both of which are involved in the degradation of proteins marked by ASB-3. Auranofin induces oxidative stress, which can directly affect the function of many proteins, including ASB-3.