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The proteasome in ubiquitin-proteasome system (UPS) has been validated as an attractive therapeutic target for cancer therapy since FDA approved Bortezomib,Carfilzomib and Ixazomib for the treatment of multiple myeloma in 2003,2012 and 2015,respectively.Among them,Carfilzomib has been proved to be able to overcome bortezomib resistance and caused fewer side effects,especially low rates of peripheral neuropathy,which gained a strong interest in the development of improved proteasome inhibitors for clinical use.