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Overview
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Background
CEP-18770 is a novel, potent and reversible P2 threonine boronic acid inhibitor of proteasome that inhibits proteasome’s chymotrypsin-like activity, with the value of inhibition constant IC50 of 3.8 nM, by down-modulating the activity of nuclear factor-KB (NF-KB) as well as the expression of a few NF-KB downstream effectors. Preliminary results of multiple studies have shown that CEP-18770 exerts potent antitumor activities against human multiple myeloma (MM) cell lines by inducing apoptotic cell death, exhibits a strong antiangiogenic activity suppressing RANKL-induced osteoclastogenesis, and displays a favorable cytotoxicity profile towards normal cells including epithelial cells, bone marrow progenitors, and bone marrow-derived stromal cells.
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