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dc.contributor.authorGuiguemde, W Armand
dc.contributor.authorShelat, Anang A
dc.contributor.authorBouck, David
dc.contributor.authorDuffy, Sandra
dc.contributor.authorCrowther, Gregory J
dc.contributor.authorDavis, Paul H
dc.contributor.authorSmithson, David C
dc.contributor.authorConnelly, Michele
dc.contributor.authorClark, Julie
dc.contributor.authorZhu, Fangyi
dc.contributor.authorJimenez-Diaz, Maria B
dc.contributor.authorMartinez, Maria S
dc.contributor.authorWilson, Emily B
dc.contributor.authorTripathi, Abhai K
dc.contributor.authorGut, Jiri
dc.contributor.authorSharlow, Elizabeth R
dc.contributor.authorBathurst, Ian
dc.contributor.authorEl Mazouni, Farah
dc.contributor.authorFowble, Joseph W
dc.contributor.authorForquer, Isaac
dc.contributor.authorMcGinley, Paula L
dc.contributor.authorCastro, Steve
dc.contributor.authorAngulo-Barturen, Inigo
dc.contributor.authorFerrer, Santiago
dc.contributor.authorRosenthal, Philip J
dc.contributor.authorDeRisi, Joseph L
dc.contributor.authorSullivan, David J
dc.contributor.authorLazo, John S
dc.contributor.authorRoos, David S
dc.contributor.authorRiscoe, Michael K
dc.contributor.authorPhillips, Margaret A
dc.contributor.authorRathod, Pradipsinh K
dc.contributor.authorVan Voorhis, Wesley C
dc.contributor.authorAvery, Vicky M
dc.contributor.authorGuy, R Kiplin
dc.date.accessioned2019-04-09T00:00:31Z
dc.date.available2019-04-09T00:00:31Z
dc.date.issued2010
dc.identifier.issn0028-0836
dc.identifier.doi10.1038/nature09099
dc.identifier.urihttp://hdl.handle.net/10072/34550
dc.description.abstractMalaria caused by Plasmodium falciparum is a disease that is responsible for 880,000 deaths per year worldwide. Vaccine development has proved difficult and resistance has emerged for most antimalarial drugs. To discover new antimalarial chemotypes, we have used a phenotypic forward chemical genetic approach to assay 309,474 chemicals. Here we disclose structures and biological activity of the entire library-many of which showed potent in vitro activity against drug-resistant P. falciparum strains-and detailed profiling of 172 representative candidates. A reverse chemical genetic study identified 19 new inhibitors of 4 validated drug targets and 15 novel binders among 61 malarial proteins. Phylochemogenetic profiling in several organisms revealed similarities between Toxoplasma gondii and mammalian cell lines and dissimilarities between P. falciparum and related protozoans. One exemplar compound displayed efficacy in a murine model. Our findings provide the scientific community with new starting points for malaria drug discovery.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.publisher.placeUnited Kingdom
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom311
dc.relation.ispartofpageto315
dc.relation.ispartofjournalNature
dc.relation.ispartofvolume465
dc.rights.retentionY
dc.subject.fieldofresearchImmunogenetics (incl. genetic immunology)
dc.subject.fieldofresearchcode320406
dc.titleChemical genetics of Plasmodium falciparum
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionAccepted Manuscript (AM)
gro.rights.copyright© 2010 Nature Publishing Group. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
gro.date.issued2015-05-31T22:21:14Z
gro.hasfulltextFull Text
gro.griffith.authorDuffy, Sandra
gro.griffith.authorAvery, Vicky M.


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