{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:02:20Z","timestamp":1791414140144,"version":"4.3.3"},"reference-count":45,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"647","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:p>\n            Gepotidacin is a first-in-class triazaacenaphthylene antibacterial agent that selectively inhibits bacterial DNA gyrase and topoisomerase IV through a unique binding mode and has the potential to treat a number of bacterial diseases. Development of this new agent to treat pneumonic plague caused by\n            <jats:italic>Yersinia pestis<\/jats:italic>\n            depends on the U.S. Food and Drug Administration Animal Rule testing pathway, as testing in humans is not feasible. Here, preclinical studies were conducted in the African green monkey (AGM) inhalational model of pneumonic plague to test the efficacy of gepotidacin. AGMs infected with\n            <jats:italic>Y. pestis<\/jats:italic>\n            were dosed intravenously with gepotidacin (48, 36, or 28 milligrams\/kilogram per day) for 10 days to provide a plasma concentration that would support a rationale for a 1000 mg twice or thrice daily intravenous dose in humans or saline as a control. The primary end point was AGM survival with predefined euthanasia criteria. Secondary end points included survival duration and bacterial clearance. Gepotidacin showed activity in vitro against diverse\n            <jats:italic>Y. pestis<\/jats:italic>\n            isolates including antibiotic-resistant strains. All control animals in the inhalational plague studies succumbed to plague and were blood culture and organ culture positive for\n            <jats:italic>Y. pestis<\/jats:italic>\n            . Gepotidacin provided a 75 to 100% survival benefit with all dose regimens. All surviving animals were blood culture and organ culture negative for\n            <jats:italic>Y. pestis<\/jats:italic>\n            . Our randomized, controlled efficacy trials in the AGM pneumonic plague nonhuman primate model together with the in vitro\n            <jats:italic>Y. pestis<\/jats:italic>\n            susceptibility data support the use of gepotidacin as a treatment for pneumonic plague caused by\n            <jats:italic>Y. pestis<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.abg1787","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T17:53:55Z","timestamp":1654106035000},"source":"Crossref","is-referenced-by-count":11,"title":["Gepotidacin is efficacious in a nonhuman primate model of pneumonic plague"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4839-0266","authenticated-orcid":true,"given":"Charles","family":"Jakielaszek","sequence":"first","affiliation":[{"name":"GlaxoSmithKline Pharmaceuticals, Collegeville, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9147-7917","authenticated-orcid":true,"given":"Mohammad","family":"Hossain","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Pharmaceuticals, Collegeville, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2240-6453","authenticated-orcid":true,"given":"Lian","family":"Qian","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Pharmaceuticals, Collegeville, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2842-9063","authenticated-orcid":true,"given":"Cindy","family":"Fishman","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Pharmaceuticals, Collegeville, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0284-4357","authenticated-orcid":true,"given":"Katherine","family":"Widdowson","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Pharmaceuticals, Collegeville, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6436-8141","authenticated-orcid":true,"given":"Jamese J.","family":"Hilliard","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Pharmaceuticals, Collegeville, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Mannino","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Pharmaceuticals, Collegeville, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7558-0466","authenticated-orcid":true,"given":"Aparna","family":"Raychaudhuri","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Pharmaceuticals, Collegeville, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Carniel","sequence":"additional","affiliation":[{"name":"Yersinia Research Unit, Institut Pasteur, Paris France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8598-2861","authenticated-orcid":true,"given":"Samandra","family":"Demons","sequence":"additional","affiliation":[{"name":"U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry S.","family":"Heine","sequence":"additional","affiliation":[{"name":"U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Hershfield","sequence":"additional","affiliation":[{"name":"U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2900-0659","authenticated-orcid":true,"given":"Riccardo","family":"Russo","sequence":"additional","affiliation":[{"name":"Rutgers University School of Medicine, Newark, NJ, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Mega","sequence":"additional","affiliation":[{"name":"Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3137-2432","authenticated-orcid":true,"given":"David","family":"Revelli","sequence":"additional","affiliation":[{"name":"Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4168-9401","authenticated-orcid":true,"given":"Karen","family":"O\u2019Dwyer","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Pharmaceuticals, Collegeville, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.17.2281"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2015.11.008"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008251"},{"key":"e_1_3_3_5_2","unstructured":"World Health Organization Plague outbreak Madagascar (WHO External Situational Report Series No. 14 World Health Organization 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V.","year":"2011","unstructured":"M. V. Stundick, M. Metz, A. Sampath, J. C. Larsen, State-of-the-art therapeutic medical countermeasures for bacterial threat agents. Drug Dev. Res. 72, 361\u2013378 (2011).","journal-title":"Drug Dev. 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A. Tiffany M. Hossain M. McDonald S. Lerman E. F. Dumont Safety and pharmacokinetics of repeat escalating IV doses of GSK2140944 a novel bacterial topoisomerase inhibitor paper presented at the 54th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy American Society for Microbiology Washington DC USA 5 to 9 September 2014."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00086-19"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00199-20"},{"key":"e_1_3_3_29_2","unstructured":"H. S. Heine L. Chuvala R. Riggins M. Gwynn C. Jakielaszek K. Widdowson L. L. Miller S. A. Halasohoris J. R. Hershfield G. Z. Feuerstein In vitro activity and efficacy in a murine aerosol challenge model of a novel antibacterial GSK2140944 against Yersinia pestis paper presented at the ASM Biodefense and Emerging Diseases Research Meeting American Society for Microbiology Washington DC USA 27 to 29 January 2014."},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2020.08.019"},{"key":"e_1_3_3_31_2","unstructured":"Food and Drug Administration Center for Drug Evaluation and Research (CDER) Product Development Under the Animal Rule Guidance for Industry (Food and Drug Administration Center for Drug Evaluation and Research 2015)."},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000959"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02504-12"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00115-16"},{"key":"e_1_3_3_35_2","unstructured":"A. Barth M. Hossain C. Tiffany C. R. Perry E. F. Dumont Distribution and Exposure of Gepotidacin (GSK2140944) in Tissues and Body Fluids of Healthy and Infected Participants paper presented at the 31st European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) virtual meeting 9 to 12 July 2021."},{"key":"e_1_3_3_36_2","unstructured":"C. Jakielaszek R. Gruber K. O\u2019Dwyer L. Qian S. Demons T. Wu Novel antibiotic gepotidacin is active in vitro and efficacious in a rat aerosol challenge treatment model of Francisella tularensis infection paper presented at the ASM Biothreats Research Response and Policy Meeting American Society for Microbiology Washington DC USA 6 to 8 February 2017."},{"key":"e_1_3_3_37_2","unstructured":"R. Gruber K. O\u2019Dwyer L. Qian L. Henning S. Demons C. 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(Clinical and Laboratory Standards Institute guideline M45-A3 ed. 3 2015)."},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.184.4.1019-1027.2002"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-6-1687"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.08.049"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz1233"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.abg1787","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T18:01:44Z","timestamp":1705428104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.abg1787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6]]},"references-count":45,"journal-issue":{"issue":"647","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["10.1126\/scitranslmed.abg1787"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.abg1787","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6]]},"article-number":"eabg1787"}}