Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 May 8:9:900-7.
doi: 10.3762/bjoc.9.103. Print 2013.

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

Paul M Hershberger  1 , Satyamaheshwar Peddibhotla, E Hampton Sessions, Daniela B Divlianska, Ricardo G Correa, Anthony B Pinkerton, John C Reed, Gregory P Roth
Affiliations

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

Paul M Hershberger et al. Beilstein J Org Chem. .

Abstract

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.

Keywords: ML029; ML130; ML146; ML236; ML237.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1
Synthesis of ML029 (4).
Scheme 2
Scheme 2
Synthesis of ML236 (8).
Scheme 3
Scheme 3
Synthesis of ML237 (12).
Scheme 4
Scheme 4
Synthesis of ML130 (13).
Scheme 5
Scheme 5
Synthesis of ML146 (17).
See this image and copyright information in PMC

References

    1. Molecular Libraries Program. Available from: http://mli.nih.gov/mli/mlpcn/
    1. Tracey K J, Cerami A. Annu Rev Cell Biol. 1993;9:317–343. doi: 10.1146/annurev.cb.09.110193.001533. - DOI - PubMed
    1. Baud V, Karin M. Nat Rev Drug Discovery. 2009;8:33–40. doi: 10.1038/nrd2781. - DOI - PMC - PubMed
    1. Bonizzi G, Karin M. Trends Immunol. 2004;25:280–288. doi: 10.1016/j.it.2004.03.008. - DOI - PubMed
    1. Gilmore T D. Oncogene. 2006;25:6680–6684. doi: 10.1038/sj.onc.1209954. - DOI - PubMed

LinkOut - more resources