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dc.contributor.authorMiguel-Blanco, Celia
dc.contributor.authorMurithi, James M.
dc.contributor.authorBenavente, Ernest Diez
dc.contributor.authorAngrisano, Fiona
dc.contributor.authorSala, Katarzyna A.
dc.contributor.authorvan Schalkwyk, Donelly A.
dc.contributor.authorVanaerschot, Manu
dc.contributor.authorSchwach, Frank
dc.contributor.authorFuchter, Matthew J.
dc.contributor.authorBillker, Oliver
dc.contributor.authorSutherland, Colin J.
dc.contributor.authorCampino, Susana G.
dc.contributor.authorClark, Taane G.
dc.contributor.authorBlagborough, Andrew M.
dc.contributor.authorFidock, David A.
dc.contributor.authorHerreros, Esperanza
dc.contributor.authorGamo, Francisco Javier
dc.contributor.authorBaum, Jake
dc.contributor.authorDelves, Michael J.
dc.date.accessioned2021-01-21T17:24:26Z
dc.date.available2021-01-21T17:24:26Z
dc.date.issued2021-01-21
dc.date.submitted2020-11-23
dc.identifier.others41598-021-81343-z
dc.identifier.other81343
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/316547
dc.descriptionFunder: Public Health England; doi: https://doi.org/10.13039/501100002141
dc.descriptionFunder: European Developing Countries Trials Platform
dc.descriptionFunder: Isaac Newton Trust
dc.descriptionFunder: Alborada Fund
dc.descriptionFunder: Global Health Innovative Technology Fund; doi: https://doi.org/10.13039/501100013996
dc.descriptionFunder: Royal Society
dc.description.abstractAbstract: New antimalarial therapeutics are needed to ensure that malaria cases continue to be driven down, as both emerging parasite resistance to frontline chemotherapies and mosquito resistance to current insecticides threaten control programmes. Plasmodium, the apicomplexan parasite responsible for malaria, causes disease pathology through repeated cycles of invasion and replication within host erythrocytes (the asexual cycle). Antimalarial drugs primarily target this cycle, seeking to reduce parasite burden within the host as fast as possible and to supress recrudescence for as long as possible. Intense phenotypic drug screening efforts have identified a number of promising new antimalarial molecules. Particularly important is the identification of compounds with new modes of action within the parasite to combat existing drug resistance and suitable for formulation of efficacious combination therapies. Here we detail the antimalarial properties of DDD01034957—a novel antimalarial molecule which is fast-acting and potent against drug resistant strains in vitro, shows activity in vivo, and possesses a resistance mechanism linked to the membrane transporter PfABCI3. These data support further medicinal chemistry lead-optimization of DDD01034957 as a novel antimalarial chemical class and provide new insights to further reduce in vivo metabolic clearance.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/692/699/255/1629
dc.subject/631/154/309/2144
dc.subjectarticle
dc.titleThe antimalarial efficacy and mechanism of resistance of the novel chemotype DDD01034957
dc.typeArticle
dc.date.updated2021-01-21T17:24:25Z
prism.issueIdentifier1
prism.publicationNameScientific Reports
prism.volume11
dc.identifier.doi10.17863/CAM.63656
dcterms.dateAccepted2020-12-18
rioxxterms.versionofrecord10.1038/s41598-021-81343-z
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn2045-2322
pubs.funder-project-idBill and Melinda Gates Foundation (OPP1043501, Malaria Drug Accelerator Consortium, OPP1043501)
pubs.funder-project-idMedicines for Malaria Venture (RD/15/0017, MMV08/2800)
pubs.funder-project-idWellcome Trust (206194/Z/17/Z, 100993/Z/13/Z, ISSF fund)
pubs.funder-project-idResearch England (BloomsburySET)
pubs.funder-project-idMedical Research Council (MR/M01360X/1, MR/N00227X/1)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/R013063/1)
pubs.funder-project-idUniversity of Cambridge (JRG Scheme)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)