An ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in Caenorhabditis elegans.
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-through...
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Public Library of Science (PLoS)
2013
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oai:doaj.org-article:f50bee2317974972a3ec716e3d7e0aed2021-11-18T07:47:37ZAn ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in Caenorhabditis elegans.1932-620310.1371/journal.pone.0062166https://doaj.org/article/f50bee2317974972a3ec716e3d7e0aed2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23637990/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203High-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.Chi K LeungYing WangSiobhan MalanyAndrew DeonarineKevin NguyenStefan VasileKeith P ChoePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e62166 (2013) |
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Medicine R Science Q |
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Medicine R Science Q Chi K Leung Ying Wang Siobhan Malany Andrew Deonarine Kevin Nguyen Stefan Vasile Keith P Choe An ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in Caenorhabditis elegans. |
| description |
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. |
| format |
article |
| author |
Chi K Leung Ying Wang Siobhan Malany Andrew Deonarine Kevin Nguyen Stefan Vasile Keith P Choe |
| author_facet |
Chi K Leung Ying Wang Siobhan Malany Andrew Deonarine Kevin Nguyen Stefan Vasile Keith P Choe |
| author_sort |
Chi K Leung |
| title |
An ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in Caenorhabditis elegans. |
| title_short |
An ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in Caenorhabditis elegans. |
| title_full |
An ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in Caenorhabditis elegans. |
| title_fullStr |
An ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in Caenorhabditis elegans. |
| title_full_unstemmed |
An ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in Caenorhabditis elegans. |
| title_sort |
ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in caenorhabditis elegans. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/f50bee2317974972a3ec716e3d7e0aed |
| work_keys_str_mv |
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