From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria

Bibliographic Details
Main Author: Yalcin, Ozlem
Publication Date: 2015
Other Authors: Oronsky, Bryan, Carvalho, Leonardo J. M., Kuypers, Frans A., Scicinski, Jan, Cabrales, Pedro
Format: Article
Language: eng
Source: Repositório Institucional da FIOCRUZ (ARCA)
DOI: 10.1186/s12936-015-0720-5
Download full: https://arca.fiocruz.br/handle/icict/13386
Summary: University of California. Department of Bioengineering. San Diego, CA, USA / Koç University. School of Medicine. Istanbul, Tirkey.
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spelling Yalcin, OzlemOronsky, BryanCarvalho, Leonardo J. M.Kuypers, Frans A.Scicinski, JanCabrales, Pedro2016-03-29T15:07:09Z2016-03-29T15:07:09Z2015YALCIN, Ozlem et al. From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria. Malaria Journal, v. 14, n. 218, p. 1-12, May 2015.1475-2875https://arca.fiocruz.br/handle/icict/1338610.1186/s12936-015-0720-51475-2875engBioMed CentralFrom METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malariainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversity of California. Department of Bioengineering. San Diego, CA, USA / Koç University. School of Medicine. Istanbul, Tirkey.EpicentRx Inc. Mountain View, CA, USA.La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil.Children’s Hospital Oakland Research Institute. Oakland, CA, USA.EpicentRx Inc. Mountain View, CA, USA.University of California. Department of Bioengineering. San Diego, CA, USA.Background: The survival of malaria parasites, under substantial haem-induced oxidative stress in the red blood cells (RBCs) is dependent on the pentose phosphate pathway (PPP). The PPP is the only source of NADPH in the RBC, essential for the production of reduced glutathione (GSH) and for protection from oxidative stress. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, therefore, increases the vulnerability of erythrocytes to oxidative stress. In Plasmodium, G6PD is combined with the second enzyme of the PPP to create a unique bifunctional enzyme, named glucose-6-phosphate dehydrogenase–6-hosphogluconolactonase (G6PD-6PGL). RRx-001 is a novel, systemically non-toxic, epigenetic anticancer agent currently in Phase 2 clinical development for multiple tumour types, with activity mediated through increased nitric oxide (NO) production and PPP inhibition. The inhibition of G6PD and NO overproduction induced by RRx-001 suggested its application in cerebral malaria (CM). Methods: Plasmodium berghei ANKA (PbA) infection in C57BL/6 mice is an experimental model of cerebral malaria (ECM) with several similar pathological features to human CM. This study uses intravital microscopy methods with a closed cranial window model to quantify cerebral haemodynamic changes and leukocyte adhesion to endothelial cells in ECM. Results: RRx-001 had both single agent anti-parasitic activity and significantly increased the efficacy of artemether. In addition, RRx-001 preserved cerebral perfusion and reduced inflammation alone or combined with artemether. RRx-001's effects were associated with inhibition of PPP (G6PD and G6PD-6PGL) and by improvements in microcirculatory flow, which may be related to the NO donating properties of RRx-001. Conclusion: The results indicate that RRx-001 could be used to potentiate the anti-malarial action of artemisinin, particularly on resistant strains, and to prevent infection.Pial microcircultationAnemiaG6PDNitric oxideEpigeneticRRx-001Malária CerebralAnemiaÓxido NítricoEpigênese Genéticainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://arca.fiocruz.br/bitstreams/5b6a6579-83fe-40b5-9999-5721ea04b967/download5a560609d32a3863062d77ff32785d58MD51falseAnonymousREADORIGINALleonardo_carvalho_etal_IOC_2015.pdfleonardo_carvalho_etal_IOC_2015.pdfapplication/pdf3678147https://arca.fiocruz.br/bitstreams/88784abd-08ab-4430-a195-fb10c0bce672/download1d6784f80378fd9caea19c8ac4f4aab1MD52trueAnonymousREADTEXTleonardo_carvalho_etal_IOC_2015.pdf.txtleonardo_carvalho_etal_IOC_2015.pdf.txtExtracted texttext/plain55358https://arca.fiocruz.br/bitstreams/539673e4-9b00-4a8c-af1a-f3e7c3d72c25/download0b6a00f57d477579212e82a73293418dMD56falseAnonymousREADTHUMBNAILCapa_page-0001.jpgCapa_page-0001.jpgimage/jpeg1014368https://arca.fiocruz.br/bitstreams/173ea370-63c3-4549-a2d9-4c4dd09f96b9/download1b0af8dea9b2f4b69fbc2c4001888fadMD54falseAnonymousREADleonardo_carvalho_etal_IOC_2015.pdf.jpgleonardo_carvalho_etal_IOC_2015.pdf.jpgGenerated Thumbnailimage/jpeg5841https://arca.fiocruz.br/bitstreams/b7bfd0c9-529b-46fa-963e-80146f0815ec/downloadbf655a9ab9881870b22daf4f8f56d61eMD57falseAnonymousREADicict/133862025-07-29 23:45:24.009open.accessoai:arca.fiocruz.br:icict/13386https://arca.fiocruz.brRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352025-07-30T02:45:24Repositório Institucional da FIOCRUZ (ARCA) - 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dc.title.none.fl_str_mv From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria
title From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria
spellingShingle From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria
Yalcin, Ozlem
Pial microcircultation
Anemia
G6PD
Nitric oxide
Epigenetic
RRx-001
Malária Cerebral
Anemia
Óxido Nítrico
Epigênese Genética
title_short From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria
title_full From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria
title_fullStr From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria
title_full_unstemmed From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria
title_sort From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria
author Yalcin, Ozlem
author_facet Yalcin, Ozlem
Oronsky, Bryan
Carvalho, Leonardo J. M.
Kuypers, Frans A.
Scicinski, Jan
Cabrales, Pedro
author_role author
author2 Oronsky, Bryan
Carvalho, Leonardo J. M.
Kuypers, Frans A.
Scicinski, Jan
Cabrales, Pedro
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Yalcin, Ozlem
Oronsky, Bryan
Carvalho, Leonardo J. M.
Kuypers, Frans A.
Scicinski, Jan
Cabrales, Pedro
dc.subject.en.none.fl_str_mv Pial microcircultation
Anemia
G6PD
Nitric oxide
Epigenetic
RRx-001
topic Pial microcircultation
Anemia
G6PD
Nitric oxide
Epigenetic
RRx-001
Malária Cerebral
Anemia
Óxido Nítrico
Epigênese Genética
dc.subject.decs.none.fl_str_mv Malária Cerebral
Anemia
Óxido Nítrico
Epigênese Genética
description University of California. Department of Bioengineering. San Diego, CA, USA / Koç University. School of Medicine. Istanbul, Tirkey.
publishDate 2015
dc.date.issued.fl_str_mv 2015
dc.date.accessioned.fl_str_mv 2016-03-29T15:07:09Z
dc.date.available.fl_str_mv 2016-03-29T15:07:09Z
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.citation.fl_str_mv YALCIN, Ozlem et al. From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria. Malaria Journal, v. 14, n. 218, p. 1-12, May 2015.
dc.identifier.uri.fl_str_mv https://arca.fiocruz.br/handle/icict/13386
dc.identifier.issn.none.fl_str_mv 1475-2875
dc.identifier.doi.none.fl_str_mv 10.1186/s12936-015-0720-5
dc.identifier.eissn.none.fl_str_mv 1475-2875
identifier_str_mv YALCIN, Ozlem et al. From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria. Malaria Journal, v. 14, n. 218, p. 1-12, May 2015.
1475-2875
10.1186/s12936-015-0720-5
url https://arca.fiocruz.br/handle/icict/13386
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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