Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside

Detalhes bibliográficos
Autor(a) principal: Khandelwal, Akash
Data de Publicação: 2022
Outros Autores: 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
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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spelling 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
dc.type.driver.fl_str_mv 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
dc.rights.driver.fl_str_mv 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
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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