NF-κB activation requires the phosphorylation, polyubiquitination, and subsequent degradation of its inhibitory subunit, IκBα. Hence, inhibiting IκBα phosphorylation ultimately inhibits NF-κB’s transcriptional activity [29, 30]. IκBα phosphorylation is carried out by IKK, a serine/threonine protein kinase composed of three basic subunits: the kinases IKKα, IKKβ, and the regulatory subunit IKKγ (NEMO). The IKK activation is usually the first common step in the integration of many NF-κB-activating pathways; therefore, one strategy for inhibiting NF-κB activation is to block IKK activation. However, although more than 150 agents have been shown to inhibit NF-κB activation at the IKK step, few studies have investigated the mechanism by which a given agent can inhibit IKK or its activation. The few IKK inhibitors for which a mechanism of action is known can be divided into three general groups: adenosine triphosphate (ATP) analogs, which show some specificity for interacting with IKK; compounds that have allosteric effects on IKK structure; and compounds that interact with a specific cysteine residue (Cys-179) in the activation loop of IKKβ. ATP analogs include natural products such as β-carboline and synthetic compounds such
