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Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis
Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children and causes chronic diarrhea in AIDS patients, but the only approved treatment is ineffective in malnourished children and immunocompromised people. We here use a drug repositioning strategy and identify a promising a...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597546/ https://www.ncbi.nlm.nih.gov/pubmed/31249291 http://dx.doi.org/10.1038/s41467-019-10687-y |
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author | Lunde, Christopher S. Stebbins, Erin E. Jumani, Rajiv S. Hasan, Md Mahmudul Miller, Peter Barlow, John Freund, Yvonne R. Berry, Pamela Stefanakis, Rianna Gut, Jiri Rosenthal, Philip J. Love, Melissa S. McNamara, Case W. Easom, Eric Plattner, Jacob J. Jacobs, Robert T. Huston, Christopher D. |
author_facet | Lunde, Christopher S. Stebbins, Erin E. Jumani, Rajiv S. Hasan, Md Mahmudul Miller, Peter Barlow, John Freund, Yvonne R. Berry, Pamela Stefanakis, Rianna Gut, Jiri Rosenthal, Philip J. Love, Melissa S. McNamara, Case W. Easom, Eric Plattner, Jacob J. Jacobs, Robert T. Huston, Christopher D. |
author_sort | Lunde, Christopher S. |
collection | PubMed |
description | Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children and causes chronic diarrhea in AIDS patients, but the only approved treatment is ineffective in malnourished children and immunocompromised people. We here use a drug repositioning strategy and identify a promising anticryptosporidial drug candidate. Screening a library of benzoxaboroles comprised of analogs to four antiprotozoal chemical scaffolds under pre-clinical development for neglected tropical diseases for Cryptosporidium growth inhibitors identifies the 6-carboxamide benzoxaborole AN7973. AN7973 blocks intracellular parasite development, appears to be parasiticidal, and potently inhibits the two Cryptosporidium species most relevant to human health, C. parvum and C. hominis. It is efficacious in murine models of both acute and established infection, and in a neonatal dairy calf model of cryptosporidiosis. AN7973 also possesses favorable safety, stability, and PK parameters, and therefore, is an exciting drug candidate for treating cryptosporidiosis. |
format | Online Article Text |
id | pubmed-6597546 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65975462019-07-01 Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis Lunde, Christopher S. Stebbins, Erin E. Jumani, Rajiv S. Hasan, Md Mahmudul Miller, Peter Barlow, John Freund, Yvonne R. Berry, Pamela Stefanakis, Rianna Gut, Jiri Rosenthal, Philip J. Love, Melissa S. McNamara, Case W. Easom, Eric Plattner, Jacob J. Jacobs, Robert T. Huston, Christopher D. Nat Commun Article Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children and causes chronic diarrhea in AIDS patients, but the only approved treatment is ineffective in malnourished children and immunocompromised people. We here use a drug repositioning strategy and identify a promising anticryptosporidial drug candidate. Screening a library of benzoxaboroles comprised of analogs to four antiprotozoal chemical scaffolds under pre-clinical development for neglected tropical diseases for Cryptosporidium growth inhibitors identifies the 6-carboxamide benzoxaborole AN7973. AN7973 blocks intracellular parasite development, appears to be parasiticidal, and potently inhibits the two Cryptosporidium species most relevant to human health, C. parvum and C. hominis. It is efficacious in murine models of both acute and established infection, and in a neonatal dairy calf model of cryptosporidiosis. AN7973 also possesses favorable safety, stability, and PK parameters, and therefore, is an exciting drug candidate for treating cryptosporidiosis. Nature Publishing Group UK 2019-06-27 /pmc/articles/PMC6597546/ /pubmed/31249291 http://dx.doi.org/10.1038/s41467-019-10687-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lunde, Christopher S. Stebbins, Erin E. Jumani, Rajiv S. Hasan, Md Mahmudul Miller, Peter Barlow, John Freund, Yvonne R. Berry, Pamela Stefanakis, Rianna Gut, Jiri Rosenthal, Philip J. Love, Melissa S. McNamara, Case W. Easom, Eric Plattner, Jacob J. Jacobs, Robert T. Huston, Christopher D. Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis |
title | Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis |
title_full | Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis |
title_fullStr | Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis |
title_full_unstemmed | Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis |
title_short | Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis |
title_sort | identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597546/ https://www.ncbi.nlm.nih.gov/pubmed/31249291 http://dx.doi.org/10.1038/s41467-019-10687-y |
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