Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

Autor: Paul M. Hershberger, Satyamaheshwar Peddibhotla, E. Hampton Sessions, Daniela B. Divlianska, Ricardo G. Correa, Anthony B. Pinkerton, John C. Reed, Gregory P. Roth
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Beilstein Journal of Organic Chemistry, Vol 9, Iss 1, Pp 900-907 (2013)
Druh dokumentu: article
ISSN: 1860-5397
DOI: 10.3762/bjoc.9.103
Popis: Activation of nuclear factor-kappa B (NF-κB) and related upstream signal transduction pathways have long been associated with the pathogenesis of a variety of inflammatory diseases and has recently been implicated in the onset of cancer. This report provides a synthetic and compound-based property summary of five pathway-related small-molecule chemical probes identified and optimized within the National Institutes of Health-Molecular Libraries Probe Center Network (NIH-MLPCN) initiative. The chemical probes discussed herein represent first-in-class, non-kinase-based modulators of the NF-κB signaling pathway, which were identified and optimized through either cellular phenotypic or specific protein-target-based screening strategies. Accordingly, the resulting new chemical probes may allow for better fundamental understanding of this highly complex biochemical signaling network and could advance future therapeutic translation toward the clinical setting.
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