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

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• may allow for better fundamental understanding of this highly complex biochemical signaling network and could advance future therapeutic translation toward the clinical setting. Keywords: ML029; ML130; ML146; ML236; ML237; Introduction The Molecular Libraries Network was established in 2005 as an

• probe, including their general physicochemical and pharmacological properties, are summarized in this report. Results and Discussion Phenotypic screening for noncanonical NF-κB pathway selective inhibitors of IL-8 production in HEK 293, HEK 293T (ML029) and 697 pre-B cells (ML236 and ML237): Most

• myristic acetate (PMA)/ionomycin) and were selective toward the 697 pre-B cell line. It is interesting to note that no compounds meeting probe selectivity criteria were identified within the T cell (HEK 293T) specific assay. The first oxadiazole-based probe ML236 (8) was potent (0.035 μM) in the 697 pre-B