title: Next-generation phenotypic screening.
abstract: Phenotypic drug discovery (PDD) strategies are defined by screening and selection of hit or lead compounds based on quantifiable phenotypic endpoints without prior knowledge of the drug target. We outline the challenges associated with traditional phenotypic screening strategies and propose solutions and new opportunities to be gained by adopting modern PDD technologies. We highlight both historical and recent examples of approved drugs and new drug candidates discovered by modern phenotypic screening. Finally, we offer a prospective view of a new era of PDD underpinned by a wealth of technology advances in the areas of in vitro model development, high-content imaging and image informatics, mechanism-of-action profiling and target deconvolution.
authors.affiliation: Cancer Research UK Edinburgh Centre, Institute of Genetics & Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Warchal
authors.affiliation: Cancer Research UK Edinburgh Centre, Institute of Genetics & Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK.
authors.forename: Asier
authors.initials: A
authors.lastname: Unciti-Broceta
authors.affiliation: Cancer Research UK Edinburgh Centre, Institute of Genetics & Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK.
authors.forename: Neil O
authors.initials: NO
authors.lastname: Carragher
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000639:trends*; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000737:chemistry; D010641:Phenotype
chemical_list: D004364:Pharmaceutical Preparations
keywords: high content; image informatics; mechanism of action; pathway profiling; phenotypic; screening; target deconvolution; transcriptomics