{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:44:30Z","timestamp":1788371070501,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672063"],"award-info":[{"award-number":["81672063"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971973"],"award-info":[{"award-number":["81971973"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\"><jats:italic>Mycobacterium abscessus<\/jats:italic><\/jats:styled-content> is a multi\u2010drug resistant pathogen presenting significant treatment challenges. This study evaluated MRX\u20105, an oral prodrug of the leucyl\u2010tRNA synthetase inhibitor MRX\u20106038, for its efficacy against <jats:styled-content style=\"fixed-case\"><jats:italic>M. abscessus<\/jats:italic><\/jats:styled-content> both in\u00a0vitro and in\u00a0vivo. Stability testing of MRX\u20105 was conducted using liquid chromatography\u2013tandem mass spectrometry in Middlebrook 7H9 broth at 35\u00b0C. Following this, the minimum inhibitory concentrations of MRX\u20105 were determined against two reference strains and 17 clinical isolates of <jats:styled-content style=\"fixed-case\"><jats:italic>M. abscessus<\/jats:italic><\/jats:styled-content>. In the in\u00a0vivo experiments, the pharmacokinetic properties of MRX\u20105 were assessed first, followed by efficacy testing conducted in a neutropenic BALB\/c mouse model of <jats:styled-content style=\"fixed-case\"><jats:italic>M. abscessus<\/jats:italic><\/jats:styled-content> lung infection. Remarkably, the conversion of MRX\u20105 to MRX\u20106038 in liquid broth was complete within 72\u2009h, and MRX\u20105 demonstrated reduced potency compared to MRX\u20106038 in\u00a0vitro. In\u00a0vivo, MRX\u20105 was efficiently converted to MRX\u20106038, achieving an oral bioavailability of 83.95% and significant lung distribution. In the mouse model of pulmonary <jats:styled-content style=\"fixed-case\"><jats:italic>M. abscessus<\/jats:italic><\/jats:styled-content> infection, MRX\u20105 effectively reduced bacterial load and exhibited antimicrobial activity comparable to that of linezolid. In conclusion, MRX\u20105 exhibited favourable lung distribution and in\u00a0vivo efficacy against <jats:styled-content style=\"fixed-case\"><jats:italic>M. abscessus<\/jats:italic><\/jats:styled-content>, positioning it as a promising candidate for the oral treatment of <jats:styled-content style=\"fixed-case\"><jats:italic>M. abscessus<\/jats:italic><\/jats:styled-content> infections.<\/jats:p>","DOI":"10.1111\/1440-1681.70024","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T05:22:50Z","timestamp":1739251370000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>LeuRS<\/scp>\u2010Targeting Prodrug, <scp>MRX<\/scp>\u20105, Expresses Anti\u2010<scp><i>Mycobacterium abscessus<\/i><\/scp> Activity"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2965-9901","authenticated-orcid":false,"given":"Anqi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital, School of Medicine, Tongji University  Shanghai China"},{"name":"School of Medicine, Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital, School of Medicine, Tongji University  Shanghai China"},{"name":"School of Medicine, Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital, School of Medicine, Tongji University  Shanghai China"},{"name":"School of Medicine, Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junsheng","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital, School of Medicine, Tongji University  Shanghai China"},{"name":"School of Medicine, Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shicong","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai MicuRx Pharmaceutical Co. 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