Potential pharmacological control of the NF-κB pathway.

Nuclear factor (NF)-kappaB governs the expression of numerous genes that are important for various cellular responses. Its activation is induced by a wide variety of stimuli including stress, cigarette smoke, viral and bacterial products, cytokines, free radicals, carcinogens and tumor promoters to name a few. Deregulation of the NF-kappaB pathway has been observed in and attributed to the development of a variety of human ailments including cancers, autoimmune disorders, pulmonary, cardiovascular, neurodegenerative and skin diseases. Efforts to develop modulators of NF-kappaB have yielded several candidates, some of which are currently in Phase I/II of clinical trials. In addition, it is now becoming apparent that several of the approved drugs being currently used also work, in part, owing to their ability to influence the NF-kappaB pathway. In this article, we focus on the druggable components of the NF-kappaB signaling system and on the recent development of novel therapeutics that target NF-kappaB in various diseases.