Targeting IKKβ for the treatment of rheumatoid arthritis.

Activation of the nuclear factor-κB (NF-κB) family of transcription factors results in the expression of numerous genes involved in the regulation of the innate and adaptive immune responses, and has been implicated as a key mechanism in chronic inflammatory diseases including rheumatoid arthritis (RA). The IκB kinases (IKKs) are key components in the signaling pathway by which proinflammatory stimuli, such as lipopolysaccharide and tumor necrosis factor-α lead to the activation of NF-κB. The most widely studied of the IKKs is IKKβ. Inhibitors of the kinase activity of IKKβ offer opportunities for intervention in RA, as well as other inflammatory disorders. Some examples for which the most extensive data are available will here be reviewed.