Inhibition of NF-κB activation by blockade of IKKβ-NEMO interactions at the NEMO binding domain

摘要

The invention includes compositions and methods for the selective inhibition of cytokine-mediated NF-κB activation by blocking the interaction of NEMO with IκB kinase-β (IKKβ) at the NEMO binding domain (NBD). The blockade of IKKβ-NEMO interaction resulting in inhibition of IKKβ kinase activity and subsequent decreased phosphorylation of IκB. Phosphorylation of IκB being an integral step in cytokine-mediated NF-κB activation. The invention further includes methods for screening for agents capable of interacting at the NBD and therapeutic uses for such agents in pathological disorders caused by dysregulation of NF-κB activation.