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Bortezomib was the first clinically approved 20S proteasome inhibitor drug used for its antitumor activity against several types of cancers ( The protein complex, nuclear factor-kappa B (NF-B), has a close relationship to cancer cells by acting as a key regulator of multiple pathways necessary for survival, stemness, resistance, angiogenesis and metastasis ( However, a recent study argued that the DSF/Cu complex (Cu(DDC)2 or CuET) is not a direct inhibitor of proteasomes, instead CuET targeted the p97-NPL4-UFDI pathway upstream to proteasome

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