{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:16:32Z","timestamp":1768900592797,"version":"3.49.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"806","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,7,9]]},"abstract":"<jats:p>\n            The protozoan parasite\n            <jats:italic>Trypanosoma cruzi<\/jats:italic>\n            causes Chagas disease, which is among the deadliest parasitic infections in Latin America. Current therapies are toxic and lack efficacy against the chronic stage of infection; thus, new drugs are urgently needed. Here, we describe a previously unidentified series of quinazoline compounds with potential against\n            <jats:italic>Trypanosoma cruzi<\/jats:italic>\n            and the related trypanosomatid parasites\n            <jats:italic>Trypanosoma brucei<\/jats:italic>\n            and\n            <jats:italic>Leishmania donovani<\/jats:italic>\n            . We demonstrated partial efficacy of a lead quinazoline compound in a mouse model of acute Chagas disease. Mechanism of action studies using several orthogonal approaches showed that this quinazoline compound series targeted the ATP-binding pocket of\n            <jats:italic>T. cruzi<\/jats:italic>\n            lysyl-tRNA synthetase 1 (KRS1). A high-resolution crystal structure of KRS1 bound to the drug indicated binding interactions that led to KRS1 inhibition. Our study identified KRS1 as a druggable target for treating\n            <jats:italic>T. cruzi<\/jats:italic>\n            infection in a mouse model. This quinazoline series shows potential for treating Chagas disease but will require further development to become a future treatment for this neglected disease.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adu4564","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T17:58:18Z","timestamp":1752083898000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Antitrypanosomal quinazolines targeting lysyl-tRNA synthetase show partial efficacy in a mouse model of acute Chagas disease"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7223-5106","authenticated-orcid":true,"given":"Lindsay B.","family":"Tulloch","sequence":"first","affiliation":[{"name":"Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee DD1 5EH, 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