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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...

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Autores principales: Gardner, J. Mark F., Mansour, Nuha R., Bell, Andrew S., Helmby, Helena, Bickle, Quentin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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.
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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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