Elsevier

SLAS Discovery

Volume 15, Issue 9, October 2010, Pages 1063-1070
SLAS Discovery

Original Articles
High-Throughput Molecular Imaging for the Identification of FADD Kinase Inhibitors

https://doi.org/10.1177/1087057110380570Get rights and content
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Fas-associated protein with death domain (FADD) was originally reported as a proapoptotic adaptor molecule that mediates receptor-induced apoptosis. Recent studies have revealed a potential role of FADD in NF-κB activation, embryogenesis, and cell cycle regulation and proliferation. Overexpression of FADD and its phosphorylation have been associated with the transformed phenotype in many cancers and is therefore a potential target for therapeutic intervention. In an effort to delineate signaling events that lead to FADD phosphorylation and to identify novel compounds that impinge on this pathway, the authors developed a cell-based reporter for FADD kinase activity. The reporter assay, optimized for a high-throughput screen (HTS), measures bioluminescence in response to modulation of FADD kinase activity in live cells. In addition, the potential use of the reporter cell line in the rapid evaluation of pharmacologic properties of HTS hits in mouse models has been demonstrated.

Key words

FADD
phosphorylation
noninvasive molecular imaging
bioluminescence
kinase activity

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These authors contributed equally to this work.