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, 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.
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