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Issue 5, 2013
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Inhibitors of transcription factor nuclear factor-kappa beta (NF-κβ)-DNA binding

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Abstract

The mammalian transcription factor nuclear factor-kappa beta (NF-κβ) 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-κβ 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 role of NF-κβ 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-κβ activation. However, approaching direct inhibition of NF-κβ- DNA binding by interfering with the DNA binding region in the NF-κβ, 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-κβ, 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-κβ-related diseases.

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

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Publication details

The article was received on 17 Aug 2012, accepted on 17 Oct 2012 and first published on 26 Oct 2012


Article type: Review Article
DOI: 10.1039/C2RA21852F
Citation: RSC Adv., 2013,3, 1282-1296
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    Inhibitors of transcription factor nuclear factor-kappa beta (NF-κβ)-DNA binding

    R. K. Sharma, M. Otsuka, G. Gaba and S. Mehta, RSC Adv., 2013, 3, 1282
    DOI: 10.1039/C2RA21852F

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