Chemical biology of inflammatory cytokine signaling

Pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-1 trigger the signal transduction pathway leading to the activation of the transcription factor, nuclear factor-kappa B (NF-kappa B). NF-kappa B induces a large number of target genes involved in many biological processes, such as inflammation, immunity, cell survival, cell death and carcinogenesis. As therapeutic agents for inflammatory diseases and cancer, as well as bioprobes for the characterization of intracellular biological response and cell function, a large number of natural and synthetic small molecules have been identified to inhibit the activation of the NF-kappa B signaling pathway. This review focuses on recent progress in the identification and biological properties of small molecules targeting the NF-kappa B signaling pathway induced by pro-inflammatory cytokines. The Journal of Antibiotics (2009) 62, 655-667; doi:10.1038/ja.2009.98; published online 16 October 2009