Recent advances and future perspectives of noncompetitive proteasome inhibitors
Gongruixue Zeng1, Qian Yu1, Rangxiao Zhuang2
1School of Medicine, Hangzhou City University, Hangzhou 310015, Zhejiang Province, China; Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China.
Abstract:
The proteasome regulates intracellular processes, maintains biological homeostasis, and has shown great significance in the study of various diseases, such as neurodegenerative diseases, immune-related diseases, and cancer, especially in hematologic malignancies such as multiple myeloma (MM) and mantle cell lymphoma (MCL). All clinically used proteasome inhibitors bind to the active site of the proteasome and thus exhibit a competitive mechanism. The development of resistance and intolerance during treatment drives the search for inhibitors with different mechanisms of action. In this review, we provide an overview of noncompetitive proteasome inhibitors, including their mechanisms of action, function, possible applications, and their advantages and disadvantages compared with competitive inhibitors.
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