Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/53144 |
Resumo: | © The Author(s) 2022. 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
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Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside3RHepaticM5717ModellingPlasmodium elongation factor 2Population PharmacokineticsSpheroids© The Author(s) 2022. 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Targeting the asymptomatic liver stage of Plasmodium infection through chemoprevention could become a key intervention to reduce malaria-associated incidence and mortality. Methods: M5717, a Plasmodium elongation factor 2 inhibitor, was assessed in vitro and in vivo with readily accessible Plasmodium berghei parasites. In an animal refinement, reduction, replacement approach, the in vitro IC99 value was used to feed a Population Pharmacokinetics modelling and simulation approach to determine meaningful effective doses for a subsequent Plasmodium sporozoite-induced volunteer infection study. Results: Doses of 100 and 200 mg would provide exposures exceeding IC99 in 96 and 100% of the simulated population, respectively. Conclusions: This approach has the potential to accelerate the search for new anti-malarials, to reduce the number of healthy volunteers needed in a clinical study and decrease and refine the animal use in the preclinical phase.This work was funded by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: https://doi.org/10.13039/100009945). F.A. is the recipient of an individual Ph.D. fellowship funded by FCT (PD/BD/128371/2017).Springer NatureRepositório da Universidade de LisboaKhandelwal, AkashArez, FranciscaAlves, Paula M.Badolo, LassinaBrito, CatarinaFischli, ChristophFontinha, DianaOeuvray, ClaudePrudêncio, MiguelRottmann, MatthiasWilkins, JustinYalkinoglu, ÖzkanBagchus, Wilhelmina M.Spangenberg, Thomas2022-05-23T16:46:24Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/53144engMalar J. 2022 May 15;21(1):15110.1186/s12936-022-04171-01475-2875info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:58:48Zoai:repositorio.ul.pt:10451/53144Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:07.667938Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside |
title |
Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside |
spellingShingle |
Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside Khandelwal, Akash 3R Hepatic M5717 Modelling Plasmodium elongation factor 2 Population Pharmacokinetics Spheroids |
title_short |
Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside |
title_full |
Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside |
title_fullStr |
Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside |
title_full_unstemmed |
Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside |
title_sort |
Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside |
author |
Khandelwal, Akash |
author_facet |
Khandelwal, Akash Arez, Francisca Alves, Paula M. Badolo, Lassina Brito, Catarina Fischli, Christoph Fontinha, Diana Oeuvray, Claude Prudêncio, Miguel Rottmann, Matthias Wilkins, Justin Yalkinoglu, Özkan Bagchus, Wilhelmina M. Spangenberg, Thomas |
author_role |
author |
author2 |
Arez, Francisca Alves, Paula M. Badolo, Lassina Brito, Catarina Fischli, Christoph Fontinha, Diana Oeuvray, Claude Prudêncio, Miguel Rottmann, Matthias Wilkins, Justin Yalkinoglu, Özkan Bagchus, Wilhelmina M. Spangenberg, Thomas |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Khandelwal, Akash Arez, Francisca Alves, Paula M. Badolo, Lassina Brito, Catarina Fischli, Christoph Fontinha, Diana Oeuvray, Claude Prudêncio, Miguel Rottmann, Matthias Wilkins, Justin Yalkinoglu, Özkan Bagchus, Wilhelmina M. Spangenberg, Thomas |
dc.subject.por.fl_str_mv |
3R Hepatic M5717 Modelling Plasmodium elongation factor 2 Population Pharmacokinetics Spheroids |
topic |
3R Hepatic M5717 Modelling Plasmodium elongation factor 2 Population Pharmacokinetics Spheroids |
description |
© The Author(s) 2022. 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-05-23T16:46:24Z 2022 2022-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/53144 |
url |
http://hdl.handle.net/10451/53144 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Malar J. 2022 May 15;21(1):151 10.1186/s12936-022-04171-0 1475-2875 |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
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