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Inhibitors of NF-κB signaling: 785 and counting

Abstract

Nuclear factor kappa B (NF-κB) transcription factors regulate several important physiological processes, including inflammation and immune responses, cell growth, apoptosis, and the expression of certain viral genes. Therefore, the NF-κB signaling pathway has also provided a focus for pharmacological intervention, primarily in situations of chronic inflammation or in cancer, where the pathway is often constitutively active and plays a key role in the disease. Now that many of the molecular details of the NF-κB pathway are known, it is clear that modulators of this pathway can act at several levels. As described herein, over 750 inhibitors of the NF-κB pathway have been identified, including a variety of natural and synthetic molecules. These compounds include antioxidants, peptides, small RNA/DNA, microbial and viral proteins, small molecules, and engineered dominant-negative or constitutively active polypeptides. Several of these molecules act as general inhibitors of NF-κB induction, whereas others inhibit specific pathways of induction. In addition, some compounds appear to target multiple steps in the NF-κB pathway. Compounds designed as specific NF-κB inhibitors are not yet in clinical use, but they are likely to be developed as treatments for certain cancers and neurodegenerative and inflammatory diseases. Moreover, the therapeutic and preventative effects of many natural products may, at least in part, be due to their ability to inhibit NF-κB.

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Acknowledgements

We thank Jean-Charles Epinat for his contributions to the 1999 version of this article. We especially thank John Porco for help with classifying the inhibitors and Melissa Chin for help with Figure 1. MH was partially supported by a Pre-doctoral Fellowship from the Natural Sciences & Engineering Research Council of Canada. Research in our laboratory is supported by a grant from the National Institutes of Health (to TDG). For a continued updating of the lists of NF-κB inhibitors, the reader is referred to our lab website at www.nfkb.org (click on INHIBITORS).

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Gilmore, T., Herscovitch, M. Inhibitors of NF-κB signaling: 785 and counting. Oncogene 25, 6887–6899 (2006). https://doi.org/10.1038/sj.onc.1209982

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