{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T18:56:56Z","timestamp":1781117816311,"version":"3.54.1"},"reference-count":34,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"853","funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-007155"],"award-info":[{"award-number":["INV-007155"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004167","name":"Medicines for Malaria Venture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004167","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004167","name":"Medicines for Malaria Venture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004167","id-type":"DOI","asserted-by":"publisher"}]},{"name":"GSK"},{"name":"Gates Foundation","award":["INV-007155"],"award-info":[{"award-number":["INV-007155"]}]},{"name":"Medicines for Malaria Venture and GSK"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,6,10]]},"abstract":"<jats:p>\n                    Fast-acting antimalarial drugs are needed to address the emergence of artemisinin resistance in the protozoan parasite\n                    <jats:italic toggle=\"yes\">Plasmodium falciparum,<\/jats:italic>\n                    the major cause of severe malaria worldwide. The pyrrolidinamide antimalarial drug MMV367 (GSK3772701) potentially interferes with parasite metabolism mediated by\n                    <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                    acyl-CoA synthetases 10 and 11. In this volunteer infection study, the antimalarial activity of MMV367 was tested against blood-stage\n                    <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                    in 12 healthy malaria-na\u00efve adults. The study participants were inoculated with\n                    <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                    3D7\u2013infected erythrocytes on day 0 and received a single oral dose of MMV367 at 3 mg (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a03), 5 mg (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a02), 10 mg (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a01), 20 mg (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a03), 90 mg (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a02), or 1500 mg (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a01) on day 8. All participants received artemether-lumefantrine on or before day 24. Maximum MMV367 plasma concentrations occurred 2 to 4 hours postdose, and the elimination half-life was 12.9 to 18 hours. For doses of \u226520 mg, the parasite clearance half-life was 2.2 to 4.3 hours with viable parasites declining more rapidly (elimination half-life of 1.1 to 2.7 hours). A clearance pharmacokinetic\/pharmacodynamic model described the relationship between MMV367 concentrations and parasite killing and subsequent clearance of nonviable parasites. Model-derived efficacy parameters included a minimum inhibitory concentration of 6.3 ng\/ml (95% CI, 5.2 to 7.8) and a minimum parasiticidal concentration with 90% of maximum effect of 54 ng\/ml (95% CI, 43 to 68). No reduction in in vitro susceptibility to MMV367 or genetic determinants of resistance were observed in drug-exposed parasite lines. Most adverse events were attributed to malaria challenge, and none were serious. Higher MMV367 doses were not associated with an increased incidence or severity of adverse events. These findings support further clinical development of MMV367.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.aec1863","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:58:11Z","timestamp":1781114291000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["The pyrrolidinamide antimalarial drug MMV367 rapidly clears blood-stage\n                    <i>Plasmodium falciparum<\/i>\n                    in healthy adults with experimental malaria"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1066-7960","authenticated-orcid":true,"given":"Bridget E.","family":"Barber","sequence":"first","affiliation":[{"name":"Department of Infection and Inflammation, QIMR Berghofer, Brisbane 4006, Australia."},{"name":"Infectious Diseases Unit, Royal Brisbane and Women\u2019s Hospital, Brisbane 4006, Australia."},{"name":"University of the Sunshine Coast Clinical Trials, Brisbane 4101, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3989-5667","authenticated-orcid":true,"given":"Robin","family":"Denhardt-Eriksson","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, 1215 Geneva 15, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8576-328X","authenticated-orcid":true,"given":"Etienne A.","family":"Guirou","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, 1215 Geneva 15, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Flynn","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, 1215 Geneva 15, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9858-1578","authenticated-orcid":true,"given":"Nischal","family":"Sahai","sequence":"additional","affiliation":[{"name":"University of the Sunshine Coast Clinical Trials, Brisbane 4101, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7786-623X","authenticated-orcid":true,"given":"Indika","family":"Leelasena","sequence":"additional","affiliation":[{"name":"University of the Sunshine Coast Clinical Trials, Brisbane 4101, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1820-199X","authenticated-orcid":true,"given":"Susan","family":"Mathison","sequence":"additional","affiliation":[{"name":"University of the Sunshine Coast Clinical Trials, Brisbane 4101, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-8512","authenticated-orcid":true,"given":"Chris","family":"Moller","sequence":"additional","affiliation":[{"name":"University of the Sunshine Coast Clinical Trials, Brisbane 4101, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9335-4459","authenticated-orcid":true,"given":"Ivan","family":"Lim","sequence":"additional","affiliation":[{"name":"University of the Sunshine Coast Clinical Trials, Brisbane 4101, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5614-935X","authenticated-orcid":true,"given":"Carla","family":"Evangelista","sequence":"additional","affiliation":[{"name":"University of the Sunshine Coast Clinical Trials, Brisbane 4101, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6715-9044","authenticated-orcid":true,"given":"Rebecca","family":"Webster","sequence":"additional","affiliation":[{"name":"Department of Infection and Inflammation, QIMR Berghofer, Brisbane 4006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J.","family":"Potter","sequence":"additional","affiliation":[{"name":"Department of Infection and Inflammation, QIMR Berghofer, Brisbane 4006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0564-947X","authenticated-orcid":true,"given":"Stacey","family":"Llewellyn","sequence":"additional","affiliation":[{"name":"Department of Infection and Inflammation, QIMR Berghofer, Brisbane 4006, Australia."},{"name":"Biostatistics and Data Science Division, George Institute for Global Health School of Population Health, University of New South Wales, Sydney 2031, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7788-5885","authenticated-orcid":true,"given":"Fiona H.","family":"Amante","sequence":"additional","affiliation":[{"name":"Department of Infection and Inflammation, QIMR Berghofer, Brisbane 4006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7414-5216","authenticated-orcid":true,"given":"Jeremy","family":"Gower","sequence":"additional","affiliation":[{"name":"Department of Infection and Inflammation, QIMR Berghofer, Brisbane 4006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Infection and Inflammation, QIMR Berghofer, Brisbane 4006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2663-1551","authenticated-orcid":true,"given":"David S.","family":"Khoury","sequence":"additional","affiliation":[{"name":"Kirby Institute, University of New South Wales, Sydney 2052, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7797-8638","authenticated-orcid":true,"given":"Vandana","family":"Thathy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York 10032, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5476-9753","authenticated-orcid":true,"given":"Sunil K.","family":"Narwal","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York 10032, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2923-6060","authenticated-orcid":true,"given":"Tomas","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York 10032, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-8938","authenticated-orcid":true,"given":"David A.","family":"Fidock","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York 10032, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Marx","sequence":"additional","affiliation":[{"name":"ICON Clinical Research, 63225 Langen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1854-2882","authenticated-orcid":true,"given":"Francisco-Javier","family":"Gamo","sequence":"additional","affiliation":[{"name":"Global Health Medicines R&amp;D, GSK, 28760 Tres Cantos, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raman","family":"Sharma","sequence":"additional","affiliation":[{"name":"GSK, Stevenage SG1 2FX, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1338-1290","authenticated-orcid":true,"given":"Rachel A.","family":"Gibson","sequence":"additional","affiliation":[{"name":"GSK, Stevenage SG1 2FX, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-5211","authenticated-orcid":true,"given":"Laura","family":"Sanz","sequence":"additional","affiliation":[{"name":"Global Health Medicines R&amp;D, GSK, 28760 Tres Cantos, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7239-0461","authenticated-orcid":true,"given":"Anthony","family":"Cahn","sequence":"additional","affiliation":[{"name":"GSK, Stevenage SG1 2FX, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Bestgen","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, 1215 Geneva 15, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9306-1851","authenticated-orcid":true,"given":"Stephan","family":"Chalon","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, 1215 Geneva 15, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"Global Malaria Programme \u201cWorld malaria report 2025\u201d (World Health Organization 2025); https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2025."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314981"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe2110659"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210956"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211803"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01099-x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2020.09.011"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-015-0874-1"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003203"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-023-00772-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09107"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36921-2"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/bcp.70000"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-016-1511-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2024.107196"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30171-8"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00679-4"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad075"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/clc.23365"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-021-04003-7"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01423-20"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa678"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00294-8"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00114-22"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.16132"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw128"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw174"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00252-8"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-024-03787-0"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-48"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-020-03291-9"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.16-0893"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04942-14"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1110574108"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.aec1863","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:58:30Z","timestamp":1781114310000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.aec1863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":34,"journal-issue":{"issue":"853","published-print":{"date-parts":[[2026,6,10]]}},"alternative-id":["10.1126\/scitranslmed.aec1863"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.aec1863","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,10]]},"assertion":[{"value":"2025-09-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaec1863"}}