Abstract
NF-κB is an important mediator of immune activity and its activation is essential in mounting immune response to pathogens. Here, we describe the optimization and implementation of a high-throughput screening platform that utilizes high content imaging and analysis to monitor NF-κB nuclear translocation. We screened 38,991 compounds from three different small molecule libraries and identified 103 compound as hits; 31% of these were active in a dose response assay. Several of the molecules lacked cytotoxicity or had a selectivity index of more than 2-fold. Our image-based approach provides an important first step towards identifying small molecules with immunomodulatory activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / drug effects
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Cell Nucleus / metabolism*
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Drug Evaluation, Preclinical / methods
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Human Umbilical Vein Endothelial Cells / cytology
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Human Umbilical Vein Endothelial Cells / metabolism*
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Humans
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Immunologic Factors* / chemistry
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Immunologic Factors* / pharmacology
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NF-kappa B / metabolism*
Substances
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Immunologic Factors
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NF-kappa B
Grants and funding
This work was supported by the Life Sciences Discovery Fund [Grant Number 19547899], the M. J. Murdock Charitable Trust, and the Washington Research Foundation.
http://www.lsdfa.org/;
https://murdocktrust.org/;
http://www.wrfseattle.org/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.