Targeting I kappa B kinase for the treatment of inflammatory and other disorders.

The nuclear transcription factor NF kappa B plays a critical role in the pathogenesis of a number of human disorders, particularly those with an inflammatory component. Due to the fact that I kappa B kinase (IKK)-catalyzed phosphorylation of I kappa B proteins is an essential step in the signal-induced activation of NF kappa B, targeting this kinase represents a fascinating opportunity to develop novel therapeutics. In this review, the current understanding of the role of IKK/NF kappa B in disease processes will be discussed, along with evidence demonstrating that IKK inhibitors will be efficacious in disorders ranging from rheumatoid arthritis to cancer and diabetes. Potential mechanism-based toxicities will also be discussed.