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An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes

Partridge, FA; Brown, AE; Buckingham, SD; Willis, NJ; Wynne, GM; Forman, R; Else, KJ; ... Sattelle, DB; + view all (2018) An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes. International Journal for Parasitology: Drugs and Drug Resistance , 8 (1) pp. 8-21. 10.1016/j.ijpddr.2017.11.004. Green open access

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Abstract

Parasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms. We have validated its utility by determining the efficacy of a panel of known anthelmintics against model and parasitic nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified compounds already known to have anthelmintic or anti-parasitic activity, including tolfenpyrad, auranofin, and mebendazole; and 14 compounds previously undescribed as anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel anthelmintics.

Type: Article
Title: An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ijpddr.2017.11.004
Publisher version: https://doi.org/10.1016/j.ijpddr.2017.11.004
Language: English
Additional information: © 2017 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
Keywords: Parasitic nematodes; C. elegans; Chemical library screening; Automated phenotyping; Anthelmintic; Benzoxaborole
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
UCL > Provost and Vice Provost Offices > VP: Health
URI: https://discovery.ucl.ac.uk/id/eprint/10039277
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