Gene expression-based screening for inhibitors of PDGFR signaling.
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.
Antipova
Alena A
AA
Cancer Program, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge Center, Cambridge, MA 02142, USA. alena.antipova@appliedbiosystems.com
Stockwell
Brent R
BR
Golub
Todd R
TR
D001312:Aurintricarboxylic Acid / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical / Q000379:methods; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D001312:Aurintricarboxylic Acid; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D048049:Extracellular Signal-Regulated MAP Kinases