Inhibitors of transcription factor nuclear factor-kappa beta (NF-κβ)-DNA binding

The mammalian transcription factor nuclear factor-kappa beta (NF-kappa beta) is an ubiquitous transcription factor responsible for the regulation of over 150 genes, impacting virtually every aspect of cellular adaptation, including responses to stress, inflammatory stimuli, activation of immune cell function, programmed cell death (apoptosis), and oncogenesis. Deregulation of the NF-kappa beta pathway has been directly implicated in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, atheroscelerosis, multiple sclerosis and asthma. Given the critical roleof NF-kappa beta mediated expression of cytokines, this transcription factor has been actively pursued as a therapeutic target for various types of disorders. More than 700 compounds have been reported to inhibit NF-kappa beta activation. However, approaching direct inhibition of NF-kappa beta-DNA binding by interfering with the DNA binding region in the NF-kappa beta, seems to be more potent and amenable to the design of specific inhibitors. Moreover, trace elements play essential roles in regulation of cell signaling mechanisms via NF-kappa beta, because of which metal chelators exert diverse and pleiotropic effects on its signaling pathways and thus have been intensely studied as a potential tool in the treatment of numerous NF-kappa beta-related diseases.