{"entity": "researcher", "timestamp": "2026-09-23T23:52:19.972Z", "family": "Lang", "given": "Pauline A", "initials": "PA", "orcid": "0000-0003-3187-1469", "affiliations": ["Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/28abfcb6da9b459d8a16e60ddba63f7d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/28abfcb6da9b459d8a16e60ddba63f7d"}}, "publications": [{"entity": "publication", "iuid": "befabca596b1481dbe2d78880a6a8fe1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/befabca596b1481dbe2d78880a6a8fe1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/befabca596b1481dbe2d78880a6a8fe1"}}, "title": "Imitation of \u03b2-lactam binding enables broad-spectrum metallo-\u03b2-lactamase inhibitors.", "authors": [{"family": "Brem", "given": "J\u00fcrgen", "initials": "J", "orcid": "0000-0002-0137-3226", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b999d433d25c4720877f5b6a9a91d6ee.json"}}, {"family": "Panduwawala", "given": "Tharindi", "initials": "T", "orcid": "0000-0001-7095-1336", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/19e7bca8e327404b9fede660f3887c19.json"}}, {"family": "Hansen", "given": "Jon Ulf", "initials": "JU"}, {"family": "Hewitt", "given": "Joanne", "initials": "J"}, {"family": "Liepins", "given": "Edgars", "initials": "E"}, {"family": "Donets", "given": "Pawel", "initials": "P", "orcid": "0000-0003-4358-2429", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9b79f40c68134baf941624313b33bb35.json"}}, {"family": "Espina", "given": "Laura", "initials": "L"}, {"family": "Farley", "given": "Alistair J M", "initials": "AJM"}, {"family": "Shubin", "given": "Kirill", "initials": "K"}, {"family": "Campillos", "given": "Gonzalo Gomez", "initials": "GG", "orcid": "0000-0002-2405-8421", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b975cef9da544136b4c0e78b716ac3ba.json"}}, {"family": "Kiuru", "given": "Paula", "initials": "P", "orcid": "0000-0001-6084-684X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ca0466ffae54f3388ab7c5780be8c02.json"}}, {"family": "Shishodia", "given": "Shifali", "initials": "S", "orcid": "0000-0001-8727-3877", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e3d81da9fe1449ebbad8beef44e65367.json"}}, {"family": "Krahn", "given": "Daniel", "initials": "D"}, {"family": "Le\u015bniak", "given": "Robert K", "initials": "RK"}, {"family": "Schmidt Adrian", "given": "Juliane", "initials": "J"}, {"family": "Calvopi\u00f1a", "given": "Karina", "initials": "K"}, {"family": "Turrientes", "given": "Mar\u00eda-Carmen", "initials": 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"initials": "TM"}, {"family": "Jimenez-Castellanos", "given": "Juan Carlos", "initials": "JC"}, {"family": "Avison", "given": "Matthew B", "initials": "MB"}, {"family": "Da Silva Pinto", "given": "Solange", "initials": "S"}, {"family": "Pannifer", "given": "Andrew D", "initials": "AD"}, {"family": "Martjuga", "given": "Marina", "initials": "M"}, {"family": "Widlake", "given": "Emma", "initials": "E", "orcid": "0000-0001-6721-8643", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a61229a08c5746fb9a0902411b2b2787.json"}}, {"family": "Priede", "given": "Martins", "initials": "M", "orcid": "0000-0002-9655-8345", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9d2f10a7152a4df1abe227a01fa89b93.json"}}, {"family": "Hopkins Navratilova", "given": "Iva", "initials": "I"}, {"family": "Gniadkowski", "given": "Marek", "initials": "M"}, {"family": "Belfrage", "given": "Anna Karin", "initials": "AK", "orcid": "0000-0002-6257-4064", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/55584bbd88db452a98b975e94f7d47a7.json"}}, {"family": "Brandt", "given": "Peter", "initials": "P", "orcid": "0000-0002-2885-2016", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/69fda8874d1a44e6887492c17e4dea2a.json"}}, {"family": "Yli-Kauhaluoma", "given": "Jari", "initials": "J", "orcid": "0000-0003-0370-7653", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1e37f790969e4af498de2b8260f23322.json"}}, {"family": "Bacque", "given": "Eric", "initials": "E"}, {"family": "Page", "given": "Malcolm G P", "initials": "MGP", "orcid": "0000-0002-0276-8174", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7c6f7d35b53549649f44044d1605f005.json"}}, {"family": "Bj\u00f6rkling", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-7018-8334", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc52b0b5aa594829b7e01787d7e56d09.json"}}, {"family": "Tyrrell", "given": "Jonathan M", "initials": "JM"}, {"family": "Spencer", "given": "James", "initials": "J", "orcid": "0000-0002-4602-0571", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c15f4b51f91e4a97b4e5f5385947c437.json"}}, {"family": "Lang", "given": "Pauline A", "initials": "PA", "orcid": "0000-0003-3187-1469", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/28abfcb6da9b459d8a16e60ddba63f7d.json"}}, {"family": "Baranczewski", "given": "Pawel", "initials": "P", "orcid": "0000-0001-5772-6791", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/327feae3833d425c9d5936f48627390c.json"}}, {"family": "Cant\u00f3n", "given": "Rafael", "initials": "R", "orcid": "0000-0003-1675-3173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/43de3f7302444428a5c4104eb81c42e3.json"}}, {"family": "McElroy", "given": "Stuart P", "initials": "SP"}, {"family": "Jones", "given": "Philip S", "initials": "PS"}, {"family": "Baquero", "given": "Fernando", "initials": "F"}, {"family": "Suna", "given": "Edgars", "initials": "E", "orcid": "0000-0002-3078-0576", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/91beaefa8b2846709b4fd35d147f1e25.json"}}, {"family": "Morrison", "given": "Angus", "initials": "A"}, {"family": "Walsh", "given": "Timothy R", "initials": "TR"}, {"family": "Schofield", "given": "Christopher J", "initials": "CJ", "orcid": "0000-0002-0290-6565", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/78f0ed7fbda741e29e0d2dde3e946d06.json"}}], "type": "journal article", "published": "2022-01-00", "journal": {"title": "Nat Chem", "issn": "1755-4349", "volume": "14", "issue": "1", "pages": "15-24", "issn-l": null}, "abstract": "Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-\u03b2-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential \u03b2-lactamase stable \u03b2-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.", "doi": "10.1038/s41557-021-00831-x", "pmid": "34903857", "labels": [], "xrefs": [{"db": "pii", "key": "10.1038/s41557-021-00831-x"}], "notes": [], "created": "2026-09-23T07:47:18.691Z", "modified": "2026-09-23T07:47:19.629Z"}]}