title: An ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in Caenorhabditis elegans.
abstract: High-throughput screening (HTS) is a powerful approach to drug discovery, but many lead compounds are found to be unsuitable for use in vivo after initial screening. Screening in small animals like C. elegans can help avoid these problems, but this system has been limited to screens with low-throughput or no specific molecular target. We report the first in vivo 1536-well plate assay for a specific genetic pathway in C. elegans. Our assay measures induction of a gene regulated by SKN-1, a master regulator of detoxification genes. SKN-1 inhibitors will be used to study and potentially reverse multidrug resistance in parasitic nematodes. Screens of two small commercial libraries and the full Molecular Libraries Small Molecule Repository (MLSMR) of ∼364,000 compounds validate our platform for ultra HTS. Our platform overcomes current limitations of many whole-animal screens and can be widely adopted for other inducible genetic pathways in nematodes and humans.
authors: Department of Biology and Genetics Institute, University of Florida, Gainesville, Florida, United States of America.
authors: Chi K
authors: CK
authors: Leung
authors: Ying
authors: Y
authors: Wang
authors: Siobhan
authors: S
authors: Malany
authors: Andrew
authors: A
authors: Deonarine
authors: Kevin
authors: K
authors: Nguyen
authors: Stefan
authors: S
authors: Vasile
authors: Keith P
authors: KP
authors: Choe
mesh_terms: D020106:Acrylamide / Q000494:pharmacology; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004355:Drug Stability; D005786:Gene Expression Regulation / Q000187:drug effects; D018869:Heat-Shock Response / Q000187:drug effects / Q000235:genetics; D057166:High-Throughput Screening Assays / Q000379:methods*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D054852:Small Molecule Libraries / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D029742:Caenorhabditis elegans Proteins; D054852:Small Molecule Libraries; D020106:Acrylamide; D013755:Tetradecanoylphorbol Acetate
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