The ubiquitin-proteasome pathway (UPP), which influences essential cellular functions including cell growth,
differentiation, apoptosis, signal transduction, antigen processing and inflammatory responses, has been considered as one
of the most important cellular protein degradation approaches. Proteasome functions as a gatekeeper, which controls the
execution of protein degradation and plays a critical role in the ubiquitin-proteasome pathway. The unfolding of the close
connection between proteasome and cancer provides a potential strategy for cancer treatment by using proteasome inhibitors.
Small molecular inhibitors of varied structures and potency against proteasome have been discovered in recent years,
with bortezomib and carfilzomib having been successfully approved for clinical application while some other promising
candidates are currently under clinical trials. Herein, we review the development history of drugs and candidates that target
the 20S proteasome, structure-activity relationships (SARs) of various proteasome inhibitors, and related completed or
ongoing clinical trials.
Keywords: Cancer, clinical development, marketed, proteasome, proteasome inhibitor, SAR.
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