Small Molecule Binding To Inhibitor Of Nuclear Factor Kappa-B Kinase Subunit Beta In An Atp Non-Competitive Manner

Inhibitor of nuclear factor kappa-B kinase subunit beta (IKK beta) is a key regulator of the cannonical NF-kappa B pathway. IKK beta has been validated as a drug target for pathological conditions, which include chronic inflammatory diseases and cancer. Pharmacological studies revealed that chronic administration of ATP-competitive IKK beta inhibitors resulted in unexpected toxicity. We previously reported the discovery of 13-197 as a non-toxic IKK beta inhibitor that reduced tumor growth. Here, we show that 13-197 inhibits IKK beta in a ATP non-competitive manner and an allosteric pocket at the interface of the kinase and ubiquitin like domains was identified as the potential binding site.