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 IC₅₀of 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.

Reference

[1].Piva R, Ruggeri B, Williams M, Costa G, Tamagno I, Ferrero D, Giai V, Coscia M, Peola S, Massaia M, Pezzoni G, Allievi C, Pescalli N, Cassin M, di Giovine S, Nicoli P, de Feudis P, Strepponi I, Roato I, Ferracini R, Bussolati B, Camussi G, Jones-Bolin S, Hunter K, Zhao H, Neri A, Palumbo A, Berkers C, Ovaa H, Bernareggi A, Inghirami G. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood. 2008;111(5):2765-2775