title: Zebrafish small molecule screens: Taking the phenotypic plunge.
abstract: Target based chemical screens are a mainstay of modern drug discovery, but the effectiveness of this reductionist approach is being questioned in light of declines in pharmaceutical R & D efficiency. In recent years, phenotypic screens have gained increasing acceptance as a complementary/alternative approach to early drug discovery. We discuss the various model organisms used in phenotypic screens, with particular focus on zebrafish, which has emerged as a leading model ofin vivophenotypic screens. Additionally, we anticipate therapeutic opportunities, particularly in orphan disease space, in the context of rapid advances in human Mendelian genetics, electronic health record (EHR)-enabled genome-phenome associations, and genome editing.
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Williams
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Research Medicine, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Hong
keywords: High-throughput screening; Phenome-wide association study; Phenotypic screening; Whole-organism screening