Proteasome Inhibitors: An Expanding Army Attacking a Unique Target

Proteasomes, large proteolytic complexes, have become significant targets for therapeutic intervention, with the 26S proteasome comprising a 20S core and 19S regulatory particles. Diverse inhibitors targeting the 20S core's active sites have been identified, including bortezomib, which is clinically used for multiple myeloma, mantle cell lymphoma, and acute allograft rejection. New proteasome inhibitors are in trials for myeloma and other cancers. These inhibitors also show promise in animal models for autoimmune and inflammatory diseases, reperfusion injury, and promoting bone and hair growth, with potential as anti-infectives. Additionally, inhibitors targeting ATPases and deubiquitinases of the 19S particles have been discovered.