Abstract
Here we describe a proof-of-concept experiment designed to explore the possibility of using gene expression-based high-throughput screening (GE-HTS) to find inhibitors of a signaling cascade, using platelet derived growth factor receptor (PDGFR) signaling as the example. The previously unrecognized ability of aurintricarboxylic acid to inhibit PDGFR signaling, discovered through a screen of 1,739 compounds, demonstrates the feasibility and generalizability of GE-HTS for the discovery of small molecule modulators of any signaling pathway of interest.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aurintricarboxylic Acid / chemistry
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Aurintricarboxylic Acid / pharmacology*
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Cell Line, Tumor
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Drug Evaluation, Preclinical / methods
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression / drug effects*
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Humans
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / isolation & purification*
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Protein Kinase Inhibitors / pharmacology*
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Receptor, Platelet-Derived Growth Factor alpha / agonists
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Receptor, Platelet-Derived Growth Factor alpha / antagonists & inhibitors*
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Receptor, Platelet-Derived Growth Factor alpha / genetics
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Receptor, Platelet-Derived Growth Factor beta / agonists
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Receptor, Platelet-Derived Growth Factor beta / antagonists & inhibitors*
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Receptor, Platelet-Derived Growth Factor beta / genetics
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Signal Transduction / drug effects
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Structure-Activity Relationship
Substances
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Protein Kinase Inhibitors
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Aurintricarboxylic Acid
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Receptor, Platelet-Derived Growth Factor alpha
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Receptor, Platelet-Derived Growth Factor beta
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Extracellular Signal-Regulated MAP Kinases