{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:26:26Z","timestamp":1791296786341,"version":"4.1.0"},"reference-count":46,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T00:00:00Z","timestamp":1464048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T00:00:00Z","timestamp":1464048000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T00:00:00Z","timestamp":1464048000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["079838"],"award-info":[{"award-number":["079838"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["092340"],"award-info":[{"award-number":["092340"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>There is an urgent requirement for safe, oral and cost-effective drugs for the treatment of visceral leishmaniasis (VL). We report that delamanid (OPC-67683), an approved drug for multi-drug resistant tuberculosis, is a potent inhibitor of Leishmania donovani both in vitro and in vivo. Twice-daily oral dosing of delamanid at 30 mg kg-1 for 5 days resulted in sterile cures in a mouse model of VL. Treatment with lower doses revealed a U-shaped (hormetic) dose-response curve with greater parasite suppression at 1 mg kg-1 than at 3 mg kg-1 (5 or 10 day dosing). Dosing delamanid for 10 days confirmed the hormetic dose-response and improved the efficacy at all doses investigated. Mechanistic studies reveal that delamanid is rapidly metabolised by parasites via an enzyme, distinct from the nitroreductase that activates fexinidazole. Delamanid has the potential to be repurposed as a much-needed oral therapy for VL.<\/jats:p>","DOI":"10.7554\/elife.09744","type":"journal-article","created":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T06:59:07Z","timestamp":1464073147000},"source":"Crossref","is-referenced-by-count":75,"title":["The anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis"],"prefix":"10.7554","volume":"5","author":[{"given":"Stephen","family":"Patterson","sequence":"first","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom"},{"name":"Drug Discovery Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8810-5605","authenticated-orcid":true,"given":"Susan","family":"Wyllie","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Norval","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laste","family":"Stojanovski","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom"},{"name":"Drug Discovery Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick RC","family":"Simeons","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom"},{"name":"Drug Discovery Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L","family":"Auer","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Osuna-Cabello","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom"},{"name":"Drug Discovery Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D","family":"Read","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom"},{"name":"Drug Discovery Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5134-0329","authenticated-orcid":true,"given":"Alan H","family":"Fairlamb","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom"},{"name":"Drug Discovery Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2016,5,24]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1128\/CMR.00061-07","article-title":"The relationship between leishmaniasis and AIDS: The second 10 years","volume":"21","author":"Alvar","year":"2008","journal-title":"Clinical Microbiology Reviews"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"e35671","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its incidence","volume":"7","author":"Alvar","year":"2012","journal-title":"PloS One"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.ijpddr.2014.02.002","article-title":"Drug repurposing and human parasitic protozoan diseases","volume":"4","author":"Andrews","year":"2014","journal-title":"International Journal for Parasitology. 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