{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:55:15Z","timestamp":1790261715204,"version":"4.1.0"},"reference-count":26,"publisher":"American Chemical Society (ACS)","issue":"1","license":[{"start":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T00:00:00Z","timestamp":1543536000000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccby_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["099212\/Z\/12"],"award-info":[{"award-number":["099212\/Z\/12"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The clinical effectiveness of carbapenem antibiotics such as meropenem is becoming increasingly compromised by the spread of both metallo-\u03b2-lactamase (MBL) and serine-\u03b2-lactamase (SBL) enzymes on mobile genetic elements, stimulating research to find new \u03b2-lactamase inhibitors to be used in conjunction with carbapenems and other \u03b2-lactam antibiotics. Herein, we describe our initial exploration of a novel chemical series of metallo-\u03b2-lactamase inhibitors, from concept to efficacy, in a survival model using an advanced tool compound (ANT431) in conjunction with meropenem.<\/jats:p>","DOI":"10.1021\/acsinfecdis.8b00246","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T16:25:52Z","timestamp":1542212752000},"page":"131-140","source":"Crossref","is-referenced-by-count":59,"title":["SAR Studies Leading to the Identification of a Novel\nSeries of Metallo-\u03b2-lactamase Inhibitors for the Treatment of\nCarbapenem-Resistant Enterobacteriaceae Infections That Display Efficacy\nin an Animal Infection Model"],"prefix":"10.1021","volume":"5","author":[{"given":"Simon","family":"Leiris","sequence":"first","affiliation":[{"name":"Antabio SAS , 436 rue Pierre et Marie Curie , ,","place":["Labe\u0300ge, France, 31670"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1960-2485","authenticated-orcid":true,"given":"Alicia","family":"Coelho","sequence":"additional","affiliation":[{"name":"Antabio SAS , 436 rue Pierre et Marie Curie , ,","place":["Labe\u0300ge, France, 31670"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6298-6384","authenticated-orcid":true,"given":"Je\u0301ro\u0302me","family":"Castandet","sequence":"additional","affiliation":[{"name":"Antabio SAS , 436 rue Pierre et Marie Curie , ,","place":["Labe\u0300ge, France, 31670"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mae\u0308lle","family":"Bayet","sequence":"additional","affiliation":[{"name":"Antabio SAS , 436 rue Pierre et Marie Curie , ,","place":["Labe\u0300ge, France, 31670"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Lozano","sequence":"additional","affiliation":[{"name":"Antabio SAS , 436 rue Pierre et Marie Curie , ,","place":["Labe\u0300ge, France, 31670"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Bougnon","sequence":"additional","affiliation":[{"name":"Antabio SAS , 436 rue Pierre et Marie Curie , ,","place":["Labe\u0300ge, France, 31670"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Bousquet","sequence":"additional","affiliation":[{"name":"Antabio SAS , 436 rue Pierre et Marie Curie , ,","place":["Labe\u0300ge, France, 31670"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2002-1805","authenticated-orcid":true,"given":"Martin","family":"Everett","sequence":"additional","affiliation":[{"name":"Antabio SAS , 436 rue Pierre et Marie Curie , ,","place":["Labe\u0300ge, France, 31670"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8587-9864","authenticated-orcid":true,"given":"Marc","family":"Lemonnier","sequence":"additional","affiliation":[{"name":"Antabio SAS , 436 rue Pierre et Marie Curie , ,","place":["Labe\u0300ge, France, 31670"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Sprynski","sequence":"additional","affiliation":[{"name":"Antabio SAS , 436 rue Pierre et Marie Curie , ,","place":["Labe\u0300ge, France, 31670"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Zalacain","sequence":"additional","affiliation":[{"name":"Antabio SAS , 436 rue Pierre et Marie Curie , ,","place":["Labe\u0300ge, France, 31670"]},{"name":"Zala Drug Discovery Consulting LLC , , ,","place":["West Chester, Pennsylvania, United States, 19380"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5153-7965","authenticated-orcid":true,"given":"Thomas David","family":"Pallin","sequence":"additional","affiliation":[{"name":"Charles River Laboratories , 8-9 The Spire Green Centre , ,","place":["Harlow, United Kingdom, CM19 5TR"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Cramp","sequence":"additional","affiliation":[{"name":"Charles River Laboratories , 8-9 The Spire Green Centre , ,","place":["Harlow, United Kingdom, CM19 5TR"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Jennings","sequence":"additional","affiliation":[{"name":"Charles River Laboratories , 8-9 The Spire Green Centre , ,","place":["Harlow, United Kingdom, CM19 5TR"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-5638","authenticated-orcid":true,"given":"Gilles","family":"Raphy","sequence":"additional","affiliation":[{"name":"Charles River Laboratories , 8-9 The Spire Green Centre , ,","place":["Harlow, United Kingdom, CM19 5TR"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9946-9463","authenticated-orcid":true,"given":"Mark W.","family":"Jones","sequence":"additional","affiliation":[{"name":"Charles River Laboratories , 8-9 The Spire Green Centre , ,","place":["Harlow, United Kingdom, CM19 5TR"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9925-2704","authenticated-orcid":true,"given":"Ramesh","family":"Pattipati","sequence":"additional","affiliation":[{"name":"GVK Biosciences Private Limited , Plot No. 28 A , , ,","place":["IDA Nacharam, Hyderabad, India, 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31670"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2018,11,14]]},"reference":[{"key":"2026090304031552400_cit1","unstructured":"O\u2019Neill, J.\n           (2016)  Review on Antimicrobial Resistance, Antimicrobial Resistance:\nTackling a Crisis for the Health and Wealth of Nations. For\nthis seminal review of antibacterial resistance, see https:\/\/amr-review.org\/Publications.html (accessed June 28, 2018)."},{"key":"2026090304031552400_cit2","unstructured":"CARB-X. https:\/\/www.phe.gov\/about\/barda\/CARB-X\/Pages\/default.aspx (accessed\nJune 28, 2018)."},{"key":"2026090304031552400_cit3","unstructured":"Biomedical Advanced\nResearch and Development Authority. http:\/\/www.phe.gov\/about\/barda\/Pages\/default.aspx (accessed June 28, 2018)."},{"key":"2026090304031552400_cit4","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1128\/AAC.01009-09","article-title":"Updated\nfunctional classification of beta-lactamases","volume":"54","author":"Bush","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026090304031552400_cit5","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1093\/jac\/8.1.81","article-title":"The combination of clavulanic acid and amoxycillin\n(Augmentin) in the treatment of patients infected with penicillinase\nproducing gonococci","volume":"8","author":"De Koning","year":"1981","journal-title":"J. Antimicrob. Chemother."},{"issue":"3","key":"2026090304031552400_cit6","doi-asserted-by":"publisher","first-page":"506","DOI":"10.2165\/00003495-199447030-00008","article-title":"Piperacillin\/tazobactam.\nA review of its antibacterial\nactivity, pharmacokinetic properties and therapeutic potential","volume":"47","author":"Bryson","year":"1994","journal-title":"Drugs"},{"issue":"6","key":"2026090304031552400_cit7","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1586\/17512433.2015.1090874","article-title":"Ceftazidime-avibactam\nfor the treatment of complicated urinary tract infections and complicated\nintra-abdominal infections","volume":"8","author":"Mawal","year":"2015","journal-title":"Expert Rev. Clin.\nPharmacol."},{"issue":"9","key":"2026090304031552400_cit8","doi-asserted-by":"publisher","first-page":"e00567","DOI":"10.1128\/AAC.00567-17","article-title":"Meropenem-Vaborbactam\nTested against Contemporary Gram-Negative Isolates Collected Worldwide\nduring 2014, Including Carbapenem-Resistant, KPC-Producing, Multidrug-Resistant,\nand Extensively Drug-Resistant Enterobacteriaceae","volume":"61","author":"Castanheira","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026090304031552400_cit9","unstructured":"Hackel, M., and Sahm, D. (2018)  In\nvitro activity of cefepime in combination with VNRX-5133 against meropenem\nand\/or cefepime resistant clinical isolates of Pseuodomonas aeruginosa; Poster Presentation ECCMID 2018, April 21\u221224; Madrid, Spain, Abstract P1543 (European\nSociety of Clinical Microbiology and Infectious Diseases)."},{"key":"2026090304031552400_cit10","doi-asserted-by":"publisher","first-page":"12406","DOI":"10.1038\/ncomms12406","article-title":"Structural basis of metallo-\u03b2-lactamase,\nserine-\u03b2-lactamase and penicillin-binding protein inhibition\nby cyclic boronates","volume":"7","author":"Brem","year":"2016","journal-title":"Nat. Commun."},{"key":"2026090304031552400_cit11","doi-asserted-by":"publisher","first-page":"249856","DOI":"10.1155\/2014\/249856","article-title":"Worldwide\ndissemination of the NDM-type\ncarbapenemases in Gram-negative bacteria","volume":"2014","author":"Dortet","year":"2014","journal-title":"BioMed\nRes. Int."},{"key":"2026090304031552400_cit12","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.drup.2017.11.002","article-title":"An update on \u03b2-lactamase\ninhibitor discovery\nand development","volume":"36","author":"Docquier","year":"2018","journal-title":"Drug Resist. Updates"},{"issue":"7","key":"2026090304031552400_cit13","doi-asserted-by":"publisher","first-page":"7267","DOI":"10.1021\/acs.jmedchem.7b00407","article-title":"Dipicolinc\nacid derivatives as inhibitors of New Delhi Metallo-betalactamase-1","volume":"60","author":"Chen","year":"2017","journal-title":"J. Med. Chem."},{"issue":"6","key":"2026090304031552400_cit14","doi-asserted-by":"publisher","first-page":"2136","DOI":"10.1128\/AAC.00866-06","article-title":"Competitive\ninhibitors of the CphA\nmetallo-\u03b2-lactamase from Aeromonas hydrophila","volume":"51","author":"Horsfall","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"issue":"5","key":"2026090304031552400_cit15","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s00204-003-0443-1","article-title":"High-dose\nclastogenic activity of aniline in the rat bone marrow and its relationship\nto the carcinogenicity in the spleen of rats","volume":"77","author":"Bomhard","year":"2003","journal-title":"Arch. Toxicol."},{"issue":"11","key":"2026090304031552400_cit16","doi-asserted-by":"publisher","first-page":"4582","DOI":"10.1128\/AAC.00511-10","article-title":"Efficacy of\nCalcium-EDTA as an Inhibitor\nfor Metallo-\u03b2-Lactamase in a Mouse Model of Pseudomonas aeruginosa Pneumonia","volume":"54","author":"Aoki","year":"2010","journal-title":"Antimicrob. Agents\nChemother."},{"key":"2026090304031552400_cit17","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/nature13445","article-title":"Aspergillomarasmine\nA overcomes metallo-\u03b2-lactamase antibiotic resistance","volume":"510","author":"King","year":"2014","journal-title":"Nature"},{"key":"2026090304031552400_cit18","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1254\/jjp.63.187","article-title":"Pharmacological profiles of aspergillomarasmines as endothelin converting\nenzyme inhibitors","volume":"63","author":"Ashikawa","year":"1993","journal-title":"Jpn. J. Pharmacol."},{"key":"2026090304031552400_cit19","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1128\/AAC.02379-15","article-title":"Multiyear,\nMultinational Survey of the Incidence and Global Distribution of Metallo-\u03b2-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa","volume":"60","author":"Kazmierczak","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"issue":"1","key":"2026090304031552400_cit20","doi-asserted-by":"publisher","first-page":"e01849","DOI":"10.1128\/AAC.01849-17","article-title":"Clinical Evolution of New Delhi Metallo-\u03b2-Lactamase\n(NDM) Optimizes Resistance under Zn(II) Deprivation","volume":"62","author":"Bahr","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026090304031552400_cit21","doi-asserted-by":"publisher","first-page":"12606","DOI":"10.1074\/jbc.RA118.003835","article-title":"Evolution of New\nDelhi metallo-\u03b2-lactamase\n(NDM) in the clinic: effects of NDM mutations on stability, zinc affinity,\nmono-zinc activity","volume":"293","author":"Cheng","year":"2018","journal-title":"J. Biol. Chem."},{"issue":"7","key":"2026090304031552400_cit22","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.tips.2018.03.007","article-title":"The Continuing\nChallenge of Metallo-\u03b2-Lactamase Inhibition: Mechanism Matters","volume":"39","author":"Ju","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"issue":"5","key":"2026090304031552400_cit23","doi-asserted-by":"publisher","first-page":"e00074","DOI":"10.1128\/AAC.00074-18","article-title":"Discovery of a novel\nmetallo-\u03b2-lactamase inhibitor,\nwhich can potentiate Meropenem activity against carbapenem-resistant Enterobacteriaceae","volume":"62","author":"Everett","year":"2018","journal-title":"Antimicrob. Agents\nChemother."},{"key":"2026090304031552400_cit24","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1093\/jac\/dkg067","article-title":"On functional and structural heterogeneity\nof VIM-type metallo-\u03b2-lactamases","volume":"51","author":"Docquier","year":"2003","journal-title":"J. Antimicrob.\nChemother."},{"key":"2026090304031552400_cit25","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.jmb.2007.11.012","article-title":"The three-dimensional\nstructure of VIM-2, a Zn-\u03b2-lactamase from Pseudomonas aeruginosa in its reduced and oxidised form","volume":"375","author":"Garcia-Saez","year":"2008","journal-title":"J. Mol. Biol."},{"key":"2026090304031552400_cit26","doi-asserted-by":"publisher","first-page":"4343","DOI":"10.1128\/AAC.00409-10","article-title":"High-resolution crystal structure\nof the subclass B3 metallo-\u03b2-lactamase BJP-1: rational basis\nfor substrate specificity and interaction with sulfonamides","volume":"54","author":"Docquier","year":"2010","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["ACS Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsinfecdis.8b00246","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/5\/1\/131\/67183173\/acsinfecdis.8b00246.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/5\/1\/131\/67183173\/acsinfecdis.8b00246.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:03:24Z","timestamp":1788422604000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article\/5\/1\/131\/1430944\/SAR-Studies-Leading-to-the-Identification-of-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,14]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,11,14]]},"published-print":{"date-parts":[[2019,1,11]]}},"URL":"https:\/\/doi.org\/10.1021\/acsinfecdis.8b00246","relation":{},"ISSN":["2373-8227"],"issn-type":[{"value":"2373-8227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,14]]}}}