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The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species
Treatment and control of schistosomiasis depends on a single drug, praziquantel, but this is not ideal for several reasons including lack of potency against the juvenile stage of the parasite, dose size, and risk of resistance. We have optimised the properties of a series of compounds we discovered...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321398/ https://www.ncbi.nlm.nih.gov/pubmed/34280206 http://dx.doi.org/10.1371/journal.pntd.0009490 |
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author | Gardner, J. Mark F. Mansour, Nuha R. Bell, Andrew S. Helmby, Helena Bickle, Quentin |
author_facet | Gardner, J. Mark F. Mansour, Nuha R. Bell, Andrew S. Helmby, Helena Bickle, Quentin |
author_sort | Gardner, J. Mark F. |
collection | PubMed |
description | Treatment and control of schistosomiasis depends on a single drug, praziquantel, but this is not ideal for several reasons including lack of potency against the juvenile stage of the parasite, dose size, and risk of resistance. We have optimised the properties of a series of compounds we discovered through high throughput screening and have designed candidates for clinical development. The best compounds demonstrate clearance of both juvenile and adult S. mansoni worms in a mouse model of infection from a single oral dose of < 10 mg/kg. Several compounds in the series are predicted to treat schistosomiasis in humans across a range of species with a single oral dose of less than 5 mg/kg. |
format | Online Article Text |
id | pubmed-8321398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-83213982021-07-31 The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species Gardner, J. Mark F. Mansour, Nuha R. Bell, Andrew S. Helmby, Helena Bickle, Quentin PLoS Negl Trop Dis Research Article Treatment and control of schistosomiasis depends on a single drug, praziquantel, but this is not ideal for several reasons including lack of potency against the juvenile stage of the parasite, dose size, and risk of resistance. We have optimised the properties of a series of compounds we discovered through high throughput screening and have designed candidates for clinical development. The best compounds demonstrate clearance of both juvenile and adult S. mansoni worms in a mouse model of infection from a single oral dose of < 10 mg/kg. Several compounds in the series are predicted to treat schistosomiasis in humans across a range of species with a single oral dose of less than 5 mg/kg. Public Library of Science 2021-07-19 /pmc/articles/PMC8321398/ /pubmed/34280206 http://dx.doi.org/10.1371/journal.pntd.0009490 Text en © 2021 Gardner et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gardner, J. Mark F. Mansour, Nuha R. Bell, Andrew S. Helmby, Helena Bickle, Quentin The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species |
title | The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species |
title_full | The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species |
title_fullStr | The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species |
title_full_unstemmed | The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species |
title_short | The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species |
title_sort | discovery of a novel series of compounds with single-dose efficacy against juvenile and adult schistosoma species |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321398/ https://www.ncbi.nlm.nih.gov/pubmed/34280206 http://dx.doi.org/10.1371/journal.pntd.0009490 |
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