title: Identification of therapeutic small-molecule leads in cultured cells using multiplexed pathway reporter readouts.
abstract: The rapid expansion of molecular screening libraries in size and complexity in the last decade has outpaced the discovery rate of cost-effective strategies to single out reagents with sought-after cellular activities. In addition to representing high-priority therapeutic targets, intensely studied cell signaling systems encapsulate robust reference points for mapping novel chemical activities given our deep understanding of the molecular mechanisms that support their activity. In this chapter, we describe strategies for using transcriptional reporters of several well-interrogated signal transduction pathways coupled with high-throughput biochemical assays to fingerprint novel compounds for drug target identification agendas.
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd. NL07.138B, Dallas, TX, 75390-9039, USA.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Kulak
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lum
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015870:Gene Expression; D017930:Genes, Reporter; D057166:High-Throughput Screening Assays; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects*; D054852:Small Molecule Libraries; D014162:Transfection
chemical_list: D054852:Small Molecule Libraries; D008156:Luciferases