Gene expression-based screening for inhibitors of PDGFR signaling

Alena A Antipova¹^,2^,3^,6 , Brent R Stockwell⁴ and Todd R Golub¹^,2^,5

¹Cancer Program, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge Center, Cambridge, MA 02142, USA

²Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Binney Street, Boston, MA 02115, USA

³Department of Chemistry, Massachusetts Institute of Technology, Massachusetts Avenue, Cambridge, MA 02139, USA

⁴Departments of Biological Sciences and Chemistry, Columbia University, Fairchild Center MC2406, Amsterdam Avenue, New York, NY 10027, USA

⁵Howard Hughes Medical Institute, Jones Boulevard, Chevy Chase, MD 20815, USA

⁶Current address: Advanced Genetic Analysis, Applied Biosystems, Cummings Center, Beverly, MA 01915, USA

author email corresponding author email

Genome Biology 2008, 9:R47doi:10.1186/gb-2008-9-3-r47


Published:	1 March 2008

Subject areas: Cell biology, Genetics, Molecular biology

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.