Triterpenoid CDDO-Me Blocks the NF-κB Pathway by Direct Inhibition of IKKβ on Cys-179

摘要: The novel oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9,-dien-28-oic acid (CDDO) and the C-28 methyl ester (CDDO-Me) induce apoptosis of human tumor cells by disruption redox balance are currently in clinical trials. present studies show that CDDO CDDO-Me block necrosis factorα-induced targeting NF-κB p65 to nucleus. also blocked factor α-induced phosphorylation IκBα. In concert with these results, we found inhibits IκBα kinaseβ (IKKβ) activity cells. support a direct mechanism, inhibited recombinant IKKβ vitro. results demonstrate (i) form adducts IKKβ, but not mutation Cys-179 Ala, (ii) mechanism dependent on oxidation Cys-179. These findings indicate directly thereby pathway interacting activation loop.