{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T03:42:16Z","timestamp":1792208536837,"version":"4.4.0"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:p>\n                    Repurposing drugs whose clinical safety has been established offers a valuable approach to reduce the cost and time associated with the development of new drugs for malaria. Here, we investigate the potential to repurpose the anticancer kinase inhibitor berzosertib for the treatment of malaria, by assessing whether a predicted efficacious human dose for malaria is within the clinically established safety and tolerability profile. First, an oral dose fractionation study was performed in a\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    \u2010infected humanized mouse model to evaluate the antimalarial pharmacokinetic\u2010pharmacodynamic properties of berzosertib. The activity of berzosertib was shown to be strongly dependent on the time in which the concentrations remain above the minimum parasiticidal concentration (MPC). A human physiologically based pharmacokinetic model was then developed and used to simulate the exposure\u2010response relationships and determine the effective human dose which fulfilled the target pharmacokinetic profile of sustained concentrations above the MPC. Our prediction indicates that six daily intravenous doses of 75\u2009mg of berzosertib will be required for the treatment of an uncomplicated blood stage malaria infection, which is comparatively lower than the clinical maximum tolerated dose for cancer therapy, which was identified as 440\u2009mg administered intravenously twice weekly over a 21\u2010day\u2009cycle for up to 18\u2009weeks. Despite berzosertib's potential for repurposing, further preclinical development is necessary to ensure it meets the standard of current and emerging antimalarials.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70303","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:49:18Z","timestamp":1777902558000},"page":"1315-1325","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repurposing Drugs for Malaria through a Human Dose Prediction: A Case Study with Berzosertib"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9569-8866","authenticated-orcid":false,"given":"Devasha","family":"Redhi","sequence":"first","affiliation":[{"name":"South African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine University of Cape Town  Cape Town South 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