{"entity": "researcher", "timestamp": "2026-09-23T22:43:03.724Z", "family": "Baranczewski", "given": "Pawel", "initials": "P", "orcid": "0000-0001-5772-6791", "affiliations": ["Department of Pharmacy, SciLifeLab Drug Discovery and Development Platform, ADME of Therapeutics Facility, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/327feae3833d425c9d5936f48627390c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/327feae3833d425c9d5936f48627390c"}}, "publications": [{"entity": "publication", "iuid": "bdf3cb94b9174341ab174b54af83f9e4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/bdf3cb94b9174341ab174b54af83f9e4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/bdf3cb94b9174341ab174b54af83f9e4"}}, "title": "AlphaFold accelerated discovery of psychotropic agonists targeting the trace amine-associated receptor 1.", "authors": [{"family": "D\u00edaz-Holgu\u00edn", "given": "Alejandro", "initials": "A", "orcid": "0000-0002-3449-5086", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/049a8f250afa402fb1813f9a0288dcb0.json"}}, {"family": "Saarinen", "given": "Marcus", "initials": "M"}, {"family": "Vo", "given": "Duc Duy", "initials": "DD"}, {"family": "Sturchio", "given": "Andrea", "initials": "A"}, {"family": "Branzell", "given": "Niclas", "initials": "N"}, {"family": "Cabeza de Vaca", "given": "Israel", "initials": "I", "orcid": "0000-0002-6208-1091", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/defa085f944942239696861994f25e79.json"}}, {"family": "Hu", "given": "Huabin", "initials": "H"}, {"family": "Mitjavila-Dom\u00e8nech", "given": "N\u00faria", "initials": "N"}, {"family": "Lindqvist", "given": "Annika", "initials": "A", "orcid": "0009-0003-2587-8434", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/89bd045cc7844e508c837da8a2887a22.json"}}, {"family": "Baranczewski", "given": "Pawel", "initials": "P", "orcid": "0000-0001-5772-6791", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/327feae3833d425c9d5936f48627390c.json"}}, {"family": "Millan", "given": "Mark J", "initials": "MJ"}, {"family": "Yang", "given": "Yunting", "initials": "Y", "orcid": "0000-0001-5700-1547", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b69ec9e8f589441482276a35ef678124.json"}}, {"family": "Carlsson", "given": "Jens", "initials": "J", "orcid": "0000-0003-4623-2977", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/792c1cd4aca248dc94b967115ffa82df.json"}}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b01bbacfa24e4b9794734bf1121d1c38.json"}}], "type": "journal article", "published": "2024-08-09", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "10", "issue": "32", "pages": "eadn1524", "issn-l": "2375-2548"}, "abstract": "Artificial intelligence is revolutionizing protein structure prediction, providing unprecedented opportunities for drug design. To assess the potential impact on ligand discovery, we compared virtual screens using protein structures generated by the AlphaFold machine learning method and traditional homology modeling. More than 16 million compounds were docked to models of the trace amine-associated receptor 1 (TAAR1), a G protein-coupled receptor of unknown structure and target for treating neuropsychiatric disorders. Sets of 30 and 32 highly ranked compounds from the AlphaFold and homology model screens, respectively, were experimentally evaluated. Of these, 25 were TAAR1 agonists with potencies ranging from 12 to 0.03 \u03bcM. The AlphaFold screen yielded a more than twofold higher hit rate (60%) than the homology model and discovered the most potent agonists. A TAAR1 agonist with a promising selectivity profile and drug-like properties showed physiological and antipsychotic-like effects in wild-type but not in TAAR1 knockout mice. These results demonstrate that AlphaFold structures can accelerate drug discovery.", "doi": "10.1126/sciadv.adn1524", "pmid": "39110804", "labels": {"SciLifeLab Fellow": "", "Jens Carlsson": ""}, "xrefs": [{"db": "pmc", "key": "PMC11305387"}], "notes": [], "created": "2026-09-23T08:42:45.034Z", "modified": "2026-09-23T08:42:45.344Z"}, {"entity": "publication", "iuid": "be2ceb3b1c964e8f8848075df52aa2eb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/be2ceb3b1c964e8f8848075df52aa2eb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/be2ceb3b1c964e8f8848075df52aa2eb"}}, "title": "Antibiotic class with potent in vivo activity targeting lipopolysaccharide synthesis in Gram-negative bacteria.", "authors": [{"family": "Huseby", "given": "Douglas L", "initials": "DL", "orcid": "0000-0001-9974-578X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a46951ada9ef48b081abd9a244d45cc1.json"}}, {"family": "Cao", "given": "Sha", "initials": "S"}, {"family": "Zamaratski", "given": "Edouard", "initials": "E", "orcid": "0009-0003-2707-3648", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8fa8570c2f0748b4b7258afa6da4702e.json"}}, {"family": "Sooriyaarachchi", "given": "Sanjeewani", "initials": "S"}, {"family": "Ahmad", "given": "Shabbir", "initials": "S", "orcid": "0000-0003-2374-1197", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9a9fa8ea9eb43fa9642ff3da5618267.json"}}, {"family": "Bergfors", "given": "Terese", "initials": "T", "orcid": "0000-0002-6463-9116", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e78b0675662e47bab61d190df5cb2203.json"}}, {"family": "Krasnova", "given": "Laura", "initials": "L"}, {"family": "Pelss", "given": "Juris", "initials": "J"}, {"family": "Ikaunieks", "given": "Martins", "initials": "M"}, {"family": "Loza", "given": "Einars", "initials": "E"}, {"family": "Katkevics", "given": "Martins", "initials": "M", "orcid": "0000-0003-1547-0075", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac9168c241174ebfad578a075c78ae4a.json"}}, {"family": "Bobileva", "given": "Olga", "initials": "O", "orcid": "0000-0001-9600-1603", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22e7bc2a9a0b47d19241789339a361bf.json"}}, {"family": "Cirule", "given": "Helena", "initials": "H"}, {"family": "Gukalova", "given": "Baiba", "initials": "B", "orcid": "0000-0002-7057-4726", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b5941a1c14d74cfe92b33c496e4ce5bc.json"}}, {"family": "Grinberga", "given": "Solveiga", "initials": "S"}, {"family": "Backlund", "given": "Maria", "initials": "M", "orcid": "0000-0002-6253-816X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3cbe928d448a4669908f38d58bbe5606.json"}}, {"family": "Simoff", "given": "Ivailo", "initials": "I"}, {"family": "Leber", "given": "Anna T", "initials": "AT"}, {"family": "Berruga-Fern\u00e1ndez", "given": "Tal\u00eda", "initials": "T"}, {"family": "Antonov", "given": "Dmitry", "initials": "D"}, {"family": "Konda", "given": "Vivekananda R", "initials": "VR"}, {"family": "Lindstr\u00f6m", "given": "Stefan", "initials": "S", "orcid": "0009-0009-7396-9529", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/63b366b7f46948b8ba5648412eab63a1.json"}}, {"family": "Olanders", "given": "Gustav", "initials": "G", "orcid": "0000-0003-4713-8368", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/67abdf5c2573420a89754f75647c04c9.json"}}, {"family": "Brandt", "given": "Peter", "initials": "P"}, {"family": "Baranczewski", "given": "Pawel", "initials": "P", "orcid": "0000-0001-5772-6791", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/327feae3833d425c9d5936f48627390c.json"}}, {"family": "Vingsbo Lundberg", "given": "Carina", "initials": "C", "orcid": "0000-0003-3408-3353", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eaa8939eb68b4d4a818ce784e6c7aaa0.json"}}, {"family": "Liepinsh", "given": "Edgars", "initials": "E", "orcid": "0000-0003-2213-8337", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3e6a02475a5a423bbc75a9b3de350e2b.json"}}, {"family": "Suna", "given": "Edgars", "initials": "E"}, {"family": "Jones", "given": "T Alwyn", "initials": "TA"}, {"family": "Mowbray", "given": "Sherry L", "initials": "SL", "orcid": "0000-0002-0732-6367", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/93f59b3d476e43f1bdf90e120e92e165.json"}}, {"family": "Hughes", "given": "Diarmaid", "initials": "D", "orcid": "0000-0002-7456-9182", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3977477b57784a1bb16dece0d61c5896.json"}}, {"family": "Karl\u00e9n", "given": "Anders", "initials": "A", "orcid": "0000-0001-9512-6981", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/032040a93855408fb5955bb3e8893431.json"}}], "type": "journal article", "published": "2024-04-09", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "121", "issue": "15", "pages": "e2317274121", "issn-l": "0027-8424"}, "abstract": "Here, we describe the identification of an antibiotic class acting via LpxH, a clinically unexploited target in lipopolysaccharide synthesis. The lipopolysaccharide synthesis pathway is essential in most Gram-negative bacteria and there is no analogous pathway in humans. Based on a series of phenotypic screens, we identified a hit targeting this pathway that had activity on efflux-defective strains of Escherichia coli. We recognized common structural elements between this hit and a previously published inhibitor, also with activity against efflux-deficient bacteria. With the help of X-ray structures, this information was used to design inhibitors with activity on efflux-proficient, wild-type strains. Optimization of properties such as solubility, metabolic stability and serum protein binding resulted in compounds having potent in vivo efficacy against bloodstream infections caused by the critical Gram-negative pathogens E. coli and Klebsiella pneumoniae. Other favorable properties of the series include a lack of pre-existing resistance in clinical isolates, and no loss of activity against strains expressing extended-spectrum-\u03b2-lactamase, metallo-\u03b2-lactamase, or carbapenemase-resistance genes. Further development of this class of antibiotics could make an important contribution to the ongoing struggle against antibiotic resistance.", "doi": "10.1073/pnas.2317274121", "pmid": "38579010", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11009625"}], "notes": [], "created": "2026-09-23T10:10:26.224Z", "modified": "2026-09-23T10:48:44.118Z"}, {"entity": "publication", "iuid": "8923e25544c44ed9993b5b5c8954e17f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8923e25544c44ed9993b5b5c8954e17f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8923e25544c44ed9993b5b5c8954e17f"}}, "title": "Transfer of cetirizine/levocetirizine into human breast milk and estimation of drug exposure to infants through breastfeeding: A human lactation study from the ConcePTION project.", "authors": [{"family": "Nordeng", "given": "Hedvig", "initials": "H", "orcid": "0000-0001-6361-2918", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e149ec4deccc4c02a3d77948d4a3355d.json"}}, {"family": "Wegler", "given": "Christine", "initials": "C", "orcid": "0000-0002-2810-7518", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fcb45d19c52847f19bd5c0aa296afe10.json"}}, {"family": "Lindqvist", "given": "Annika", "initials": "A", "orcid": "0009-0003-2587-8434", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/89bd045cc7844e508c837da8a2887a22.json"}}, {"family": "Melander", "given": "Erik", "initials": "E", "orcid": "0009-0002-9981-3505", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8526de87b7914d7a9c62170c26fb9e4f.json"}}, {"family": "Magnusson", "given": "Mikaela", "initials": "M", "orcid": "0000-0003-4347-2094", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eade0faf6b75494d84a4ad63d2799040.json"}}, {"family": "Gandia", "given": "Peggy", "initials": "P", "orcid": "0000-0002-4385-7894", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b66aba78159426ca9c50d348c962a3d.json"}}, {"family": "Panchaud", "given": "Alice", "initials": "A", "orcid": "0000-0001-6086-2401", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/abd99a5f06aa401a86e0c14de367c914.json"}}, {"family": "Baranczewski", "given": "Pawel", "initials": "P", "orcid": "0000-0001-5772-6791", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/327feae3833d425c9d5936f48627390c.json"}}, {"family": "Spigset", "given": "Olav", "initials": "O", "orcid": "0000-0001-7902-9014", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4029fefdca91491896e055abda57f25d.json"}}], "type": "journal article", "published": "2024-01-00", "journal": {"title": "Basic Clin. Pharmacol. Toxicol.", "issn": "1742-7843", "volume": "134", "issue": "1", "pages": "153-164", "issn-l": "1742-7835"}, "abstract": "Data on drug transfer into human breast milk are sparse. This study aimed to quantify concentrations of cetirizine and levocetirizine in breast milk and to estimate drug exposure to infants. Breastfeeding women at least 8 weeks postpartum and using cetirizine or its pure (R)-enantiomer levocetirizine were eligible to participate. Breast milk samples were collected at six predefined times during a dose interval (0, 2, 4, 8, 12 and 24 h after drug intake) at steady state. Infant drug exposure was estimated by calculating the absolute infant dose (AID) and the weight-adjusted relative infant dose (RID). In total, 32 women were eligible for final inclusion, 31 women using cetirizine and one woman using levocetirizine. Means of the individual maximum and average cetirizine milk concentrations were 41.0 and 16.8 \u03bcg/L, respectively. Maximum concentrations occurred on average 2.4 h after intake, and the mean half-life in milk was 7.0 h. Estimated AID and RID for cetirizine in a day were 2.5 \u03bcg/kg and 1.9%, respectively. The corresponding values for levocetirizine were 1.1 \u03bcg/kg and 1.9%. No severe adverse events were reported. Our findings demonstrate that the transfer of cetirizine and levocetirizine into breast milk is low and compatible with breastfeeding.", "doi": "10.1111/bcpt.13948", "pmid": "37811726", "labels": [], "xrefs": [], "notes": [], "created": "2026-09-23T12:10:11.915Z", "modified": "2026-09-23T12:10:12.195Z"}, {"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": "MC"}, {"family": "Kavanagh", "given": "Madeline E", "initials": "ME", "orcid": "0000-0002-4735-1559", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0cfdec1007f9467fac2227584ef529dc.json"}}, {"family": "Lubriks", "given": "Dmitrijs", "initials": "D", "orcid": "0000-0002-8014-4172", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/77c4808356df4321a5358fbb65ca90c4.json"}}, {"family": "Hinchliffe", "given": "Philip", "initials": "P"}, {"family": "Langley", "given": "Gareth W", "initials": "GW", "orcid": "0000-0003-0875-3712", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d09b8ac98f194880a53f88776d22e856.json"}}, {"family": "Aboklaish", "given": "Ali F", "initials": "AF"}, {"family": "Eneroth", "given": "Anders", "initials": "A"}, {"family": "Backlund", "given": "Maria", "initials": "M", "orcid": "0000-0002-6253-816X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3cbe928d448a4669908f38d58bbe5606.json"}}, {"family": "Baran", "given": "Andrei G", "initials": "AG"}, {"family": "Nielsen", "given": "Elisabet I", "initials": "EI", "orcid": "0000-0003-0725-214X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/106402da1d3b4205a886a629c9e2d82a.json"}}, {"family": "Speake", "given": "Michael", "initials": "M"}, {"family": "Kuka", "given": "Janis", "initials": "J"}, {"family": "Robinson", "given": "John", "initials": "J"}, {"family": "Grinberga", "given": "Solveiga", "initials": "S"}, {"family": "Robinson", "given": "Lindsay", "initials": "L"}, {"family": "McDonough", "given": "Michael A", "initials": "MA", "orcid": "0000-0003-4664-6942", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/81f4c2f384e64f0d9a4e5976e0e5553a.json"}}, {"family": "Rydzik", "given": "Anna M", "initials": "AM"}, {"family": "Leissing", "given": "Thomas M", "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"}]}