{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:18:54Z","timestamp":1788931134634,"version":"build-2803163510"},"reference-count":14,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Merck Sharp & Dohme LLC, a subsidiary of Merck &amp; Co., Inc., Rahway, NJ, USA"},{"DOI":"10.13039\/100010269","name":"The Wellcome Trust","doi-asserted-by":"publisher","award":["WT- 109662\/Z\/15\/Z"],"award-info":[{"award-number":["WT- 109662\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"The Wellcome Trust","doi-asserted-by":"publisher","award":["WT- 202749\/Z\/16\/Z"],"award-info":[{"award-number":["WT- 202749\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"The Wellcome Trust","doi-asserted-by":"publisher","award":["WT- 219658\/Z\/19\/Z"],"award-info":[{"award-number":["WT- 219658\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,2,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      MK-7602 is a first-in-class dual-plasmepsin inhibitor being developed to treat malaria. Safety, tolerability, and pharmacokinetics (PK) of MK-7602 following single and multiple doses were evaluated in two phase 1 studies (7602-001; 7602-002). Study 7602-001 included two parts: part 1, a randomized, single-ascending-dose (10\u2013400 mg), placebo-controlled, double-blind study (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 24); and part 2, a non-randomized, fixed-sequence, open-label study (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 12) to assess the effect of itraconazole (200 mg), a cytochrome P450 3A and P-glycoprotein inhibitor, on the PK of MK-7602 (25 mg). Study 7602-002 was a randomized, placebo-controlled, multiple-ascending-dose study (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 40); participants received MK-7602 (50\u2013300 mg) or placebo for 7 days. Single and multiple doses of MK-7602 were generally well tolerated. Headaches were the most common adverse event (7602-001 part 1: 54.5%; 7602-002: 36.7%). MK-7602 median time to maximal concentration (\n                      <jats:italic toggle=\"yes\">T<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) was 1.5\u20133.0 h, with dose-proportional increases in maximum concentration (\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) and the area under the curve over the dosing interval (AUC\n                      <jats:sub>0-tau<\/jats:sub>\n                      ) at single and multiple doses of \u226550 mg. Terminal half-life was 31.3\u201341.4 h following multiple dosing, the accumulation ratio for daily dosing was 1.03\u20132.20, and steady-state concentrations were reached by day 3. Coadministration with itraconazole resulted in a 6- and 12-fold increase in\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      and area under the concentration-time curve to infinity, respectively. The primary hypothesis that a well-tolerated dose of MK-7602 would achieve a trough concentration of \u22650.017 \u03bcM was met in both studies. Safety and PK characteristics support continued development of MK-7602.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01261-25","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T14:02:52Z","timestamp":1768399372000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["First-in-human safety and pharmacokinetics of MK-7602, the antimalarial inhibitor of plasmepsins IX\/X, in single- and multiple-ascending-dose studies"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1344-3121","authenticated-orcid":true,"given":"Susan E.","family":"Stanley","sequence":"first","affiliation":[{"name":"MRL, Merck & Co.","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russ P.","family":"Carstens","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co.","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria V.","family":"Liberti","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co.","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ward","family":"Eertmans","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00kt5kp12","id-type":"ROR","asserted-by":"publisher"}],"name":"MSD","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrthel","family":"Vranckx","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00kt5kp12","id-type":"ROR","asserted-by":"publisher"}],"name":"MSD","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Longo","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co.","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nairita","family":"Ghosal","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co.","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa","family":"Vavrek","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co.","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Olsen","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co.","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan F.","family":"Cowman","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research","place":["Parkville, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Reynders","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00kt5kp12","id-type":"ROR","asserted-by":"publisher"}],"name":"MSD","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Cilissen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00kt5kp12","id-type":"ROR","asserted-by":"publisher"}],"name":"MSD","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine","family":"Laethem","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00kt5kp12","id-type":"ROR","asserted-by":"publisher"}],"name":"MSD","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Rottey","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00cv9y106","id-type":"ROR","asserted-by":"publisher"}],"name":"Ghent University, Ghent University Hospital","place":["Ghent, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Robbins","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co.","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Aubrey","family":"Stoch","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co.","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Nussbaum","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co.","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.161"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.943445"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-023-04639-7"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2018.10.002"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2021.05.007"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-024-04848-8"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.02.005"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2022.03.018"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.2c00355"},{"key":"e_1_3_5_11_2","volume-title":"Proceedings of the American Society of Tropical Medicine & Hygience","author":"Favuzza P","year":"2023","unstructured":"Favuzza P. 2023. Dual plasmepsin inhibitors: 3 stage malaria inhibitory potency and robust P. falciparum resistance profile. Proceedings of the American Society of Tropical Medicine & Hygience; Chicago, USA"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2025.106061"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2013.794785"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad260"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-024-03787-0"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01261-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01261-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T14:02:22Z","timestamp":1770213742000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01261-25"}},"subtitle":[],"editor":[{"given":"Audrey","family":"Odom John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":14,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2,4]]}},"alternative-id":["10.1128\/aac.01261-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.01261-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]},"assertion":[{"value":"2025-08-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01261-25"}}