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The molecular chaperone heat shock protein 90 (Hsp90) has emerged as an essential protein for blood-stage\n            <jats:named-content content-type=\"genus-species\">Plasmodium<\/jats:named-content>\n            parasites, but details about its function during malaria's elusive liver stage are unclear. We used target-based screens to identify compounds that bind to\n            <jats:named-content content-type=\"genus-species\">Plasmodium falciparum<\/jats:named-content>\n            and human Hsp90, which revealed insights into chemotypes with species-selective binding. Using cell-based malaria assays, we demonstrate that all identified Hsp90-binding compounds are liver- and blood-stage\n            <jats:named-content content-type=\"genus-species\">Plasmodium<\/jats:named-content>\n            inhibitors. Additionally, the Hsp90 inhibitor SNX-0723 in combination with the phosphatidylinositol 3-kinase inhibitor PIK-75 synergistically reduces the liver-stage parasite load. Time course inhibition studies with the Hsp90 inhibitors and expression analysis support a role for\n            <jats:named-content content-type=\"genus-species\">Plasmodium<\/jats:named-content>\n            Hsp90 in late-liver-stage parasite development. Our results suggest that\n            <jats:named-content content-type=\"genus-species\">Plasmodium<\/jats:named-content>\n            Hsp90 is essential to liver- and blood-stage parasite infections and highlight an attractive route for development of species-selective\n            <jats:italic>Pf<\/jats:italic>\n            Hsp90 inhibitors that may act synergistically in combination therapies to prevent and treat malaria.\n          <\/jats:p>","DOI":"10.1128\/aac.01799-17","type":"journal-article","created":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T08:32:51Z","timestamp":1516005171000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Identification of Hsp90 Inhibitors with Anti-Plasmodium Activity"],"prefix":"10.1128","volume":"62","author":[{"given":"Dora","family":"Posfai","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber L.","family":"Eubanks","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison I.","family":"Keim","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace Z.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip F.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Kato","sequence":"additional","affiliation":[{"name":"The Broad Institute, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Haystead","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily R.","family":"Derbyshire","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA"},{"name":"Department of Chemistry, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"World malaria report 2014","author":"WHO","year":"2014","unstructured":"WHO. 2014. 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