{"entity": "researcher", "timestamp": "2026-08-09T08:13:07.868Z", "family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "affiliations": ["Uppsala Drug Optimization and Pharmaceutical Profiling Facility (UDOPP), SciLifeLab Chemical Biology Consortium Sweden (CBCS), Department of Pharmacy, Uppsala University, 75123, Uppsala, Sweden.", "SciLifeLab Drug Discovery and Development Platform, ADME of Therapeutics facility (UDOPP), Department of Pharmacy, Uppsala University, 75123, Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8"}}, "publications": [{"entity": "publication", "iuid": "06ad0fb25bc94a7da35d862c094f74a8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/06ad0fb25bc94a7da35d862c094f74a8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/06ad0fb25bc94a7da35d862c094f74a8"}}, "title": "Human jejunal enteroids for studies of epithelial drug transport and metabolism", "authors": [{"family": "Ceylan", "given": "Merve", "initials": "M"}, {"family": "Tzioufa", "given": "Foteini", "initials": "F", "orcid": "0009-0006-6884-6821", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea7581291cc147d5a814abc0a80b91a4.json"}}, {"family": "Di Martino", "given": "Maria Letizia", "initials": "ML", "orcid": "0000-0002-9491-4000", "researcher": {"href": "https://publications.scilifelab.se/researcher/708eae058cb3494f8407574a666a16f0.json"}}, {"family": "Hammar", "given": "Rebekkah", "initials": "R", "orcid": "0000-0001-5740-0353", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d8e872219e74a5d90adc8047b1e476e.json"}}, {"family": "Lopes", "given": "Ana C C", "initials": "ACC"}, {"family": "Eriksson", "given": "Jens", "initials": "J", "orcid": "0000-0002-8945-2665", "researcher": {"href": "https://publications.scilifelab.se/researcher/b94e7f542841474d86d53aa48958f870.json"}}, {"family": "Vo", "given": "Dinh Son", "initials": "DS", "orcid": "0009-0000-4180-8231", "researcher": {"href": "https://publications.scilifelab.se/researcher/03968401df594760a9df66791cdc05b2.json"}}, {"family": "Sundbom", "given": "Magnus", "initials": "M", "orcid": "0000-0002-6243-2859", "researcher": {"href": "https://publications.scilifelab.se/researcher/a54316faa45947bd92615d27a38c2b87.json"}}, {"family": "Skogar", "given": "Martin", "initials": "M"}, {"family": "Hellstr\u00f6m", "given": "Per M", "initials": "PM"}, {"family": "Webb", "given": "Dominic Luc", "initials": "DL", "orcid": "0000-0002-6979-9194", "researcher": {"href": "https://publications.scilifelab.se/researcher/868fca24b48f440eb2417acdb04e73d3.json"}}, {"family": "Karlgren", "given": "Maria", "initials": "M", "orcid": "0000-0003-4500-0170", "researcher": {"href": "https://publications.scilifelab.se/researcher/34f36303d2f9406f8bf50eefd41c544c.json"}}, {"family": "Gardner", "given": "Iain", "initials": "I"}, {"family": "Lundquist", "given": "Patrik", "initials": "P", "orcid": "0000-0002-7458-7882", "researcher": {"href": "https://publications.scilifelab.se/researcher/f44b798ddc81465f89907c7ef52eb206.json"}}, {"family": "Hjelmqvist", "given": "Daisy", "initials": "D", "orcid": "0000-0002-2126-4385", "researcher": {"href": "https://publications.scilifelab.se/researcher/c02e61f71d0a4f1d9c39c804b9f5b808.json"}}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications.scilifelab.se/researcher/f797357bcd3d4447bff96c20873dd500.json"}}, {"family": "Hubert", "given": "Madlen", "initials": "M", "orcid": "0000-0002-5908-9535", "researcher": {"href": "https://publications.scilifelab.se/researcher/48acd1c7795b45919bba57a5a9817ea7.json"}}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8.json"}}], "type": "posted-content", "published": "2025-03-17", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.03.17.643545", "pmid": null, "labels": {"Cryo-EM": "Service", "Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [], "notes": [], "created": "2025-10-29T14:38:08.332Z", "modified": "2025-12-18T19:17:29.703Z"}, {"entity": "publication", "iuid": "8041e0533b634b6bb40ff425aec24668", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8041e0533b634b6bb40ff425aec24668.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8041e0533b634b6bb40ff425aec24668"}}, "title": "Maturation of Human Intestinal Epithelial Cell Layers Fortifies the Apical Surface againstSalmonellaAttack", "authors": [{"family": "van Rijn", "given": "Jorik M", "initials": "JM", "orcid": "0000-0003-2865-4455", "researcher": {"href": "https://publications.scilifelab.se/researcher/8f2defce179d4632a4e7d60666417ab2.json"}}, {"family": "Lopes", "given": "Ana C C", "initials": "ACC"}, {"family": "Ceylan", "given": "Merve", "initials": "M"}, {"family": "Eriksson", "given": "Jens", "initials": "J"}, {"family": "Bergholtz", "given": "Alexandra", "initials": "A"}, {"family": "Ntokaki", "given": "Angelika", "initials": "A"}, {"family": "Hammar", "given": "Rebekkah", "initials": "R", "orcid": "0000-0001-5740-0353", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d8e872219e74a5d90adc8047b1e476e.json"}}, {"family": "Sundbom", "given": "Magnus", "initials": "M", "orcid": "0000-0002-6243-2859", "researcher": {"href": "https://publications.scilifelab.se/researcher/a54316faa45947bd92615d27a38c2b87.json"}}, {"family": "Skogar", "given": "Martin", "initials": "M"}, {"family": "Graf", "given": "Wilhelm", "initials": "W"}, {"family": "Webb", "given": "Dominic Luc", "initials": "DL", "orcid": "0000-0002-6979-9194", "researcher": {"href": "https://publications.scilifelab.se/researcher/868fca24b48f440eb2417acdb04e73d3.json"}}, {"family": "Hellstr\u00f6m", "given": "Per M", "initials": "PM"}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8.json"}}, {"family": "Pelaseyed", "given": "Thaher", "initials": "T", "orcid": "0000-0002-6434-3913", "researcher": {"href": "https://publications.scilifelab.se/researcher/9dc0aa3d9762420caa7efaaa19c1174b.json"}}, {"family": "Di Martino", "given": "Maria Letizia", "initials": "ML", "orcid": "0000-0002-9491-4000", "researcher": {"href": "https://publications.scilifelab.se/researcher/708eae058cb3494f8407574a666a16f0.json"}}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications.scilifelab.se/researcher/f797357bcd3d4447bff96c20873dd500.json"}}], "type": "posted-content", "published": "2024-07-13", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2024.07.11.603014", "pmid": null, "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-07T14:56:11.381Z", "modified": "2025-12-18T19:26:59.426Z"}, {"entity": "publication", "iuid": "d18a2001ca2a484ea1267aaed4906d19", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d18a2001ca2a484ea1267aaed4906d19.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d18a2001ca2a484ea1267aaed4906d19"}}, "title": "Exploiting loss of heterozygosity for allele-selective colorectal cancer chemotherapy.", "authors": [{"family": "Rendo", "given": "Veronica", "initials": "V", "orcid": "0000-0002-2983-4020", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f3fe17dd4464af585b16916a88c34b7.json"}}, {"family": "Stoimenov", "given": "Ivaylo", "initials": "I"}, {"family": "Mateus", "given": "Andr\u00e9", "initials": "A", "orcid": "0000-0001-6870-0677", "researcher": {"href": "https://publications.scilifelab.se/researcher/d79942eca68f4b2d8c2e72cf258f1213.json"}}, {"family": "Sj\u00f6berg", "given": "Elin", "initials": "E"}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Gustavsson", "given": "Anna-Lena", "initials": "AL", "orcid": "0000-0003-4332-2336", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b014ef7ea0d461b8e2ddb87506b1252.json"}}, {"family": "Johansson", "given": "Lars", "initials": "L"}, {"family": "Ng", "given": "Adrian", "initials": "A"}, {"family": "O\u02bcBrien", "given": "Casey", "initials": "C", "orcid": "0000-0002-6572-4881", "researcher": {"href": "https://publications.scilifelab.se/researcher/5782c9d8ce674fe8ad55eba0d514da54.json"}}, {"family": "Giannakis", "given": "Marios", "initials": "M"}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8.json"}}, {"family": "Nygren", "given": "Peter", "initials": "P"}, {"family": "Cheong", "given": "Ian", "initials": "I"}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T", "orcid": "0000-0001-6668-4140", "researcher": {"href": "https://publications.scilifelab.se/researcher/909f00a5bf6e465f9ff560b12bcd863a.json"}}], "type": "journal article", "published": "2020-03-11", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "1308"}, "abstract": "Cancer chemotherapy targeting frequent loss of heterozygosity events is an attractive concept, since tumor cells may lack enzymatic activities present in normal constitutional cells. To find exploitable targets, we map prevalent genetic polymorphisms to protein structures and identify 45 nsSNVs (non-synonymous small nucleotide variations) near the catalytic sites of 17 enzymes frequently lost in cancer. For proof of concept, we select the gastrointestinal drug metabolic enzyme NAT2 at 8p22, which is frequently lost in colorectal cancers and has a common variant with 10-fold reduced activity. Small molecule screening results in a cytotoxic kinase inhibitor that impairs growth of cells with slow NAT2 and decreases the growth of tumors with slow NAT2 by half as compared to those with wild-type NAT2. Most of the patient-derived CRC cells expressing slow NAT2 also show sensitivity to 6-(4-aminophenyl)-N-(3,4,5-trimethoxyphenyl)pyrazin-2-amine (APA) treatment. These findings indicate that the therapeutic index of anti-cancer drugs can be altered by bystander mutations affecting drug metabolic genes.", "doi": "10.1038/s41467-020-15111-4", "pmid": "32161261", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-15111-4"}, {"db": "pmc", "key": "PMC7066191"}], "notes": [], "created": "2020-03-17T11:11:47.766Z", "modified": "2025-10-17T13:05:08.058Z"}, {"entity": "publication", "iuid": "44ffad7b695247d5b3a8a8f106c863ce", "links": {"self": {"href": "https://publications.scilifelab.se/publication/44ffad7b695247d5b3a8a8f106c863ce.json"}, "display": {"href": "https://publications.scilifelab.se/publication/44ffad7b695247d5b3a8a8f106c863ce"}}, "title": "A Cell-Free Approach Based on Phospholipid Characterization for Determination of the Cell Specific Unbound Drug Fraction (f u,cell).", "authors": [{"family": "Treyer", "given": "Andrea", "initials": "A", "orcid": "0000-0002-4533-7761", "researcher": {"href": "https://publications.scilifelab.se/researcher/d8850eb082b647dc8af1984229c063f1.json"}}, {"family": "Walday", "given": "Sandra", "initials": "S"}, {"family": "Boriss", "given": "Hinnerk", "initials": "H"}, {"family": "Matsson", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0002-9094-2581", "researcher": {"href": "https://publications.scilifelab.se/researcher/4dee02fddfcd47549fd31f6a7e266135.json"}}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8.json"}}], "type": "journal article", "published": "2019-11-07", "journal": {"title": "Pharm. Res.", "issn": "1573-904X", "volume": "36", "issue": "12", "pages": "178", "issn-l": "0724-8741"}, "abstract": "The intracellular fraction of unbound compound (f u,cell) is an important parameter for accurate prediction of drug binding to intracellular targets. fu,cell is the result of a passive distribution process of drug molecules partitioning into cellular structures. Initial observations in our laboratory showed an up to 10-fold difference in the fu,cell of a given drug for different cell types. We hypothesized that these differences could be explained by the phospholipid (PL) composition of the cells, since the PL cell membrane is the major sink of unspecific drug binding. Therefore, we determined the fu,cell of 19 drugs in cell types of different origin.\n\nThe cells were characterized for their total PL content and we used mass spectrometric PL profiling to delineate the impact of each of the four major cellular PL subspecies: phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI). The cell-based experiments were compared to cell-free experiments that used beads covered by PL bilayers consisting of the most abundant PL subspecies.\n\nPC was found to give the largest contribution to the drug binding. Improved correlations between the cell-based and cell-free assays were obtained when affinities to all four major PL subspecies were considered. Together, our data indicate that f u,cell is influenced by PL composition of cells.\n\nWe conclude that cellular PL composition varies between cell types and that cell-specific mixtures of PLs can replace cellular assays for determination of f u,cell as a rapid, small-scale assay covering a broad dynamic range. Graphical Abstract.", "doi": "10.1007/s11095-019-2717-1", "pmid": "31701258", "labels": {"Drug Discovery and Development": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1007/s11095-019-2717-1"}, {"db": "pmc", "key": "PMC6838048"}], "notes": [], "created": "2020-01-08T07:45:55.991Z", "modified": "2025-10-17T13:05:08.100Z"}, {"entity": "publication", "iuid": "bfeb495043cf4c5699df7e2a30f09caf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bfeb495043cf4c5699df7e2a30f09caf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bfeb495043cf4c5699df7e2a30f09caf"}}, "title": "Improved predictions of time-dependent drug-drug interactions by determination of cytosolic drug concentrations.", "authors": [{"family": "Filppula", "given": "Anne M", "initials": "AM", "orcid": "0000-0002-7932-8265", "researcher": {"href": "https://publications.scilifelab.se/researcher/26b4707474ac4045a1ae206b3c6b003d.json"}}, {"family": "Parvizi", "given": "Rezvan", "initials": "R", "orcid": "0000-0001-8650-1225", "researcher": {"href": "https://publications.scilifelab.se/researcher/24d90167ae484978a79562922cafbae5.json"}}, {"family": "Mateus", "given": "Andr\u00e9", "initials": "A", "orcid": "0000-0001-6870-0677", "researcher": {"href": "https://publications.scilifelab.se/researcher/d79942eca68f4b2d8c2e72cf258f1213.json"}}, {"family": "Baranczewski", "given": "Pawel", "initials": "P"}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8.json"}}], "type": "journal article", "published": "2019-04-10", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "9", "issue": "1", "pages": "5850", "issn-l": "2045-2322"}, "abstract": "The clinical impact of drug-drug interactions based on time-dependent inhibition of cytochrome P450 (CYP) 3A4 has often been overpredicted, likely due to use of improper inhibitor concentration estimates at the enzyme. Here, we investigated if use of cytosolic unbound inhibitor concentrations could improve predictions of time-dependent drug-drug interactions. First, we assessed the inhibitory effects of ten time-dependent CYP3A inhibitors on midazolam 1'-hydroxylation in human liver microsomes. Then, using a novel method, we determined the cytosolic bioavailability of the inhibitors in human hepatocytes, and used the obtained values to calculate their concentrations at the active site of the enzyme, i.e. the cytosolic unbound concentrations. Finally, we combined the data in mechanistic static predictions, by considering different combinations of inhibitor concentrations in intestine and liver, including hepatic concentrations corrected for cytosolic bioavailability. The results were then compared to clinical data. Compared to no correction, correction for cytosolic bioavailability resulted in higher accuracy and precision, generally in line with those obtained by more demanding modelling. The best predictions were obtained when the inhibition of hepatic CYP3A was based on unbound maximal inhibitor concentrations corrected for cytosolic bioavailability. Our findings suggest that cytosolic unbound inhibitor concentrations improves predictions of time-dependent drug-drug interactions for CYP3A.", "doi": "10.1038/s41598-019-42051-x", "pmid": "30971754", "labels": {"Drug Discovery and Development": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-019-42051-x"}, {"db": "pmc", "key": "PMC6458156"}], "notes": [], "created": "2019-11-13T15:59:58.628Z", "modified": "2025-10-17T13:05:08.237Z"}, {"entity": "publication", "iuid": "1cb24ce38acd44ed832fe09fee558741", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1cb24ce38acd44ed832fe09fee558741.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1cb24ce38acd44ed832fe09fee558741"}}, "title": "Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation.", "authors": [{"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}}, {"family": "C\u00e1zares-K\u00f6rner", "given": "Armando", "initials": "A", "orcid": "0000-0003-0765-3787", "researcher": {"href": "https://publications.scilifelab.se/researcher/59a3775a65e9430aa96ad72230029236.json"}}, {"family": "Hao", "given": "Wenjing", "initials": "W", "orcid": "0000-0002-8487-5968", "researcher": {"href": "https://publications.scilifelab.se/researcher/44953a42d8b84079af5e600b4a413ef7.json"}}, {"family": "Wallner", "given": "Olov", "initials": "O", "orcid": "0000-0002-6481-237X", "researcher": {"href": "https://publications.scilifelab.se/researcher/83eb2f7ee2f34f2cbacaae2dadcd90e9.json"}}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G", "orcid": "0000-0002-9527-2310", "researcher": {"href": "https://publications.scilifelab.se/researcher/41dcc0806dba4a56bb04725812f3a000.json"}}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Sarno", "given": "Antonio", "initials": "A", "orcid": "0000-0002-9308-8018", "researcher": {"href": "https://publications.scilifelab.se/researcher/f47cb410dce04c30bf70b85c6633d72f.json"}}, {"family": "Manoilov", "given": "Aleksandr", "initials": "A"}, {"family": "Astorga-Wells", "given": "Juan", "initials": "J", "orcid": "0000-0003-1017-8841", "researcher": {"href": "https://publications.scilifelab.se/researcher/14530d9aa03747858976b4889e959fe5.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Pan", "given": "Lang", "initials": "L"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Karsten", "given": "Stella", "initials": "S", "orcid": "0000-0001-6191-4314", "researcher": {"href": "https://publications.scilifelab.se/researcher/4cbde9247c7145ff8ea0bbc0b0c5c477.json"}}, {"family": "Gokturk", "given": "Camilla", "initials": "C"}, {"family": "Grube", "given": "Maurice", "initials": "M"}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Hanna", "given": "Bishoy M F", "initials": "BMF", "orcid": "0000-0001-7027-6553", "researcher": {"href": "https://publications.scilifelab.se/researcher/d39737c7b47549e292f1c668a48e2491.json"}}, {"family": "Paulin", "given": "Cynthia B J", "initials": "CBJ", "orcid": "0000-0002-5698-7962", "researcher": {"href": "https://publications.scilifelab.se/researcher/f54dd3938c0640f1b770a3b52baba6d9.json"}}, {"family": "Pham", "given": "Therese", "initials": "T"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW"}, {"family": "von Nicolai", "given": "Catharina", "initials": "C"}, {"family": "Benitez-Buelga", "given": "Carlos", "initials": "C"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Ivanic", "given": "Dag", "initials": "D", "orcid": "0000-0002-6052-2236", "researcher": {"href": "https://publications.scilifelab.se/researcher/aecb0c1aee9f454188e4cbc778afc22e.json"}}, {"family": "Iliev", "given": "Petar", "initials": "P", "orcid": "0000-0002-3905-9814", "researcher": {"href": "https://publications.scilifelab.se/researcher/5235dc5c5406476c958a4048eeef9e6f.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M", "orcid": "0000-0002-7073-8495", "researcher": {"href": "https://publications.scilifelab.se/researcher/87c041a8b3414f5db02873dc8013806b.json"}}, {"family": "Krokan", "given": "Hans E", "initials": "HE"}, {"family": "Baranczewski", "given": "Pawel", "initials": "P"}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8.json"}}, {"family": "Altun", "given": "Mikael", "initials": "M"}, {"family": "Jensen", "given": "Annika Jenmalm", "initials": "AJ"}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C"}, {"family": "Ba", "given": "Xueqing", "initials": "X", "orcid": "0000-0002-1075-5496", "researcher": {"href": "https://publications.scilifelab.se/researcher/5c547a402d534219905c835930d7a094.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "Boldogh", "given": "Istvan", "initials": "I"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2018-11-16", "journal": {"volume": "362", "issn": "1095-9203", "issue": "6416", "pages": "834-839", "title": "Science", "issn-l": "0036-8075"}, "abstract": "The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor-\u03b1-induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor \u03baB and proinflammatory gene expression, resulting in decreased immune cell recruitment to mouse lungs. Thus, we present a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo.", "doi": "10.1126/science.aar8048", "pmid": "30442810", "labels": {"Chemical Proteomics": "Collaborative", "Protein Science Facility (PSF)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pii", "key": "362/6416/834"}, {"db": "pmc", "key": "PMC6645780"}, {"db": "mid", "key": "NIHMS1026297"}], "notes": [], "created": "2018-11-19T09:35:21.697Z", "modified": "2025-10-17T13:05:08.336Z"}, {"entity": "publication", "iuid": "675347d3c50d42f196d814d845d3b268", "links": {"self": {"href": "https://publications.scilifelab.se/publication/675347d3c50d42f196d814d845d3b268.json"}, "display": {"href": "https://publications.scilifelab.se/publication/675347d3c50d42f196d814d845d3b268"}}, "title": "MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool.", "authors": [{"family": "Gad", "given": "Helge", "initials": "H", "orcid": "0000-0001-6530-1443", "researcher": {"href": "https://publications.scilifelab.se/researcher/6273ef3dd1574185af0a83e9ab31bfe5.json"}}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "A", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}, {"family": "Eshtad", "given": "Saeed", "initials": "S", "orcid": "0000-0001-6763-4700", "researcher": {"href": "https://publications.scilifelab.se/researcher/edf4a705cae045feb64d1d9c7f8d9646.json"}}, {"family": "Jacques", "given": "Sylvain A", "initials": "SA"}, {"family": "Str\u00f6m", "given": "Cecilia E", "initials": "CE"}, {"family": "Svensson", "given": "Linda M", "initials": "LM"}, {"family": "Schultz", "given": "Niklas", "initials": "N"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T", "orcid": "0000-0002-8145-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/e13df787cb884549bcf333aba4e6f010.json"}}, {"family": "Einarsdottir", "given": "Berglind Osk", "initials": "BO"}, {"family": "Saleh", "given": "Aljona", "initials": "A"}, {"family": "G\u00f6kt\u00fcrk", "given": "Camilla", "initials": "C", "orcid": "0000-0002-6272-9927", "researcher": {"href": "https://publications.scilifelab.se/researcher/9318cec5020f4c92b8393b20242c0d58.json"}}, {"family": "Baranczewski", "given": "Pawel", "initials": "P", "orcid": "0000-0001-5772-6791", "researcher": {"href": "https://publications.scilifelab.se/researcher/47f7af2466c14275a42aad4a431b2dcb.json"}}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Berntsson", "given": "Ronnie P-A", "initials": "RP"}, {"family": "Gustafsson", "given": "Robert", "initials": "R", "orcid": "0000-0002-4854-5531", "researcher": {"href": "https://publications.scilifelab.se/researcher/16dd7e73adad4f85972d1d546bfa6d2a.json"}}, {"family": "Str\u00f6mberg", "given": "Kia", "initials": "K"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Jacques-Cordonnier", "given": "Marie-Caroline", "initials": "M"}, {"family": "Desroses", "given": "Matthieu", "initials": "M", "orcid": "0000-0003-4152-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/b232b70751004e9ea6b547533f901376.json"}}, {"family": "Gustavsson", "given": "Anna-Lena", "initials": "A", "orcid": "0000-0003-4332-2336", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b014ef7ea0d461b8e2ddb87506b1252.json"}}, {"family": "Olofsson", "given": "Roger", "initials": "R"}, {"family": "Johansson", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-5160-9543", "researcher": {"href": "https://publications.scilifelab.se/researcher/0667c14b327f44fd8a802acd9c3f1fb2.json"}}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Br\u00e4utigam", "given": "Lars", "initials": "L"}, {"family": "Johansson", "given": "Lars", "initials": "L", "orcid": "0000-0001-7071-4699", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b9129e8ce7846e5b35b50f1ff4493e2.json"}}, {"family": "H\u00f6glund", "given": "Andreas", "initials": "A", "orcid": "0000-0002-1130-374X", "researcher": {"href": "https://publications.scilifelab.se/researcher/70a484451caf40f2a1a196b36bb9c423.json"}}, {"family": "Hagenkort", "given": "Anna", "initials": "A"}, {"family": "Pham", "given": "Therese", "initials": "T"}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications.scilifelab.se/researcher/4317b773615e476694840e907b7b1a0c.json"}}, {"family": "Gaugaz", "given": "Fabienne Z", "initials": "FZ"}, {"family": "Vikingsson", "given": "Svante", "initials": "S"}, {"family": "Evers", "given": "Bastiaan", "initials": "B"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Vallin", "given": "Karl S A", "initials": "KSA"}, {"family": "Wallner", "given": "Olov A", "initials": "OA"}, {"family": "Hammarstr\u00f6m", "given": "Lars G J", "initials": "LGJ"}, {"family": "Wiita", "given": "Elisee", "initials": "E"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C"}, {"family": "Axelsson", "given": "Hanna", "initials": "H", "orcid": "0000-0003-2365-1749", "researcher": {"href": "https://publications.scilifelab.se/researcher/63b88c4d11c443f39121c6d93fcff1f0.json"}}, {"family": "Djureinovic", "given": "Tatjana", "initials": "T"}, {"family": "Puigvert", "given": "Jordi Carreras", "initials": "JC"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M", "orcid": "0000-0002-3857-1437", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2b5f5d0486a4422b93a626a2cd1583f.json"}}, {"family": "Jeppsson", "given": "Fredrik", "initials": "F"}, {"family": "Martens", "given": "Ulf", "initials": "U"}, {"family": "Lundin", "given": "Cecilia", "initials": "C"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Granelli", "given": "Ingrid", "initials": "I"}, {"family": "Jensen", "given": "Annika Jenmalm", "initials": "AJ"}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8.json"}}, {"family": "Nilsson", "given": "Jonas A", "initials": "JA", "orcid": "0000-0003-0346-6837", "researcher": {"href": "https://publications.scilifelab.se/researcher/27f0581f25124e98b0bd0eef8c3f3331.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M", "orcid": "0000-0002-7073-8495", "researcher": {"href": "https://publications.scilifelab.se/researcher/87c041a8b3414f5db02873dc8013806b.json"}}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications.scilifelab.se/researcher/a74c79d4b11346a4918f536b5a678e12.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2014-04-10", "journal": {"volume": "508", "issn": "1476-4687", "issue": "7495", "pages": "215-221", "title": "Nature", "issn-l": "0028-0836"}, "abstract": "Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bind in the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.", "doi": "10.1038/nature13181", "pmid": "24695224", "labels": {"Protein Science Facility (PSF)": null, "Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "nature13181"}], "notes": "Uppsala Drug Optimization and Pharmaceutical Profiling (UDOPP)\r\nADME of Therapeutics (UDOPP)\r\nBiochemical and Cellular Screening", "created": "2017-05-04T14:56:52.658Z", "modified": "2025-10-23T08:56:28.795Z"}]}