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We report potent activity of the benzoxaborole AN3661 against <jats:italic>Plasmodium falciparum<\/jats:italic> laboratory-adapted strains (mean IC<jats:sub>50<\/jats:sub> 32\u2009nM), Ugandan field isolates (mean <jats:italic>ex vivo<\/jats:italic> IC<jats:sub>50<\/jats:sub> 64\u2009nM), and murine <jats:italic>P. berghei<\/jats:italic> and <jats:italic>P. falciparum<\/jats:italic> infections (day 4 ED<jats:sub>90<\/jats:sub> 0.34 and 0.57\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>, respectively). Multiple <jats:italic>P. falciparum<\/jats:italic> lines selected <jats:italic>in vitro<\/jats:italic> for resistance to AN3661 harboured point mutations in <jats:italic>pfcpsf3<\/jats:italic>, which encodes a homologue of mammalian cleavage and polyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3). CRISPR-Cas9-mediated introduction of <jats:italic>pfcpsf3<\/jats:italic> mutations into parental lines recapitulated AN3661 resistance. PfCPSF3 homology models placed these mutations in the active site, where AN3661 is predicted to bind. Transcripts for three trophozoite-expressed genes were lost in AN3661-treated trophozoites, which was not observed in parasites selected or engineered for AN3661 resistance. Our results identify the pre-mRNA processing factor PfCPSF3 as a promising antimalarial drug target.<\/jats:p>","DOI":"10.1038\/ncomms14574","type":"journal-article","created":{"date-parts":[[2017,3,6]],"date-time":"2017-03-06T10:07:19Z","timestamp":1488794839000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":145,"title":["A potent antimalarial benzoxaborole targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue"],"prefix":"10.1038","volume":"8","author":[{"given":"Ebere","family":"Sonoiki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline L.","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus C. 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