Targeting the proteasome pathway

Background: The ubiquitin-proteasome pathway functions as a main pathway in intracellular protein degradation and plays a vital role in almost all cellular events. Various inhibitors of this pathway have been developed for research purposes. The recent approval of bortezomib (PS-341, Velcade (R)), a proteasome inhibitor, for the treatment of multiple myeloma has opened the way to the discovery of drugs targeting the proteasome and other components of the ubiquitin-proteasome pathway. Objectives: We review the current understanding of the ubiquitin-proteasome pathway and inhibitors targeting this pathway, including proteasome inhibitors, as candidate drugs for chemical therapy. Methods: Preclinical and clinical data for inhibitors of the proteasome and the ubiquitin-proteasome pathway are discussed. Conclusions: The proteasome and other members in the ubiquitin-proteasome pathway have emerged as novel therapeutic targets.