{"entity": "researcher", "timestamp": "2026-04-20T21:39:08.572Z", "family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "affiliations": ["Science for Life Laboratory, Stockholm, Sweden.", "Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.", "Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05"}}, "publications": [{"entity": "publication", "iuid": "79a9f40ca8e84b22978cef973223751e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/79a9f40ca8e84b22978cef973223751e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/79a9f40ca8e84b22978cef973223751e"}}, "title": "High-content morphological profiling by Cell Painting in 3D spheroids", "authors": [{"family": "Ringers", "given": "Christa", "initials": "C", "orcid": "0000-0002-0807-8481", "researcher": {"href": "https://publications.scilifelab.se/researcher/1870bfae83214898acf048b2ecbd81ba.json"}}, {"family": "Holmberg", "given": "David", "initials": "D", "orcid": "0000-0001-7204-0026", "researcher": {"href": "https://publications.scilifelab.se/researcher/56fa719ef91e45c4bdb4171fa4a40338.json"}}, {"family": "Flobak", "given": "\u00c5smund", "initials": "\u00c5", "orcid": "0000-0002-3357-425X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3dbad688aeb44d039f3bc7e51f75b2bf.json"}}, {"family": "Georgieva", "given": "Polina", "initials": "P", "orcid": "0000-0001-8326-4738", "researcher": {"href": "https://publications.scilifelab.se/researcher/394f19ff3cff4b1c94d0a9a92e976b73.json"}}, {"family": "Jarvius", "given": "Malin", "initials": "M", "orcid": "0000-0002-1565-6155", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6b510afc21748adb6b432173c3fdab2.json"}}, {"family": "Johansson", "given": "Martin", "initials": "M", "orcid": "0000-0002-3733-8975", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1fdb7ed5e7047f3963ada15a0f8d48e.json"}}, {"family": "Larsson", "given": "Anders", "initials": "A", "orcid": "0000-0002-2096-8102", "researcher": {"href": "https://publications.scilifelab.se/researcher/f4a4e2ec44f1446e98ee05ff0f45e484.json"}}, {"family": "Ros\u00e9n", "given": "Dan", "initials": "D"}, {"family": "Seashore\u2013Ludlow", "given": "Brinton", "initials": "B", "orcid": "0000-0001-8658-5967", "researcher": {"href": "https://publications.scilifelab.se/researcher/4645bc97a8024c548111802101b83571.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}}, {"family": "Carreras Puigvert", "given": "Jordi", "initials": "J", "orcid": "0000-0002-7671-3707", "researcher": {"href": "https://publications.scilifelab.se/researcher/28ad5f6a1a064e52aca72780adc4bb96.json"}}, {"family": "Spjuth", "given": "Ola", "initials": "O", "orcid": "0000-0002-8083-2864", "researcher": {"href": "https://publications.scilifelab.se/researcher/605dbd52684d4e54ae4150a9933abe6e.json"}}], "type": "posted-content", "published": "2025-02-08", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.02.05.636642", "pmid": null, "labels": {"Chemical Biology Consortium Sweden": "Technology development"}, "xrefs": [], "notes": [], "created": "2025-04-15T11:55:48.934Z", "modified": "2025-12-18T19:20:13.620Z"}, {"entity": "publication", "iuid": "9acd4142dc314a259044f6bf390a903b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9acd4142dc314a259044f6bf390a903b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9acd4142dc314a259044f6bf390a903b"}}, "title": "MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia.", "authors": [{"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Calder\u00f3n-Monta\u00f1o", "given": "Jos\u00e9 Manuel", "initials": "JM", "orcid": "0000-0001-6845-797X", "researcher": {"href": "https://publications.scilifelab.se/researcher/474af64ef5914eb7b99f9d98bf9a7455.json"}}, {"family": "Pham", "given": "Therese M", "initials": "TM"}, {"family": "Erkers", "given": "Tom", "initials": "T"}, {"family": "Tsuber", "given": "Viktoriia", "initials": "V"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "H\u00f6glund", "given": "Andreas", "initials": "A"}, {"family": "Heshmati", "given": "Yaser", "initials": "Y"}, {"family": "Seashore-Ludlow", "given": "Brinton", "initials": "B", "orcid": "0000-0001-8658-5967", "researcher": {"href": "https://publications.scilifelab.se/researcher/4645bc97a8024c548111802101b83571.json"}}, {"family": "Nagesh Danda", "given": "Akhilesh", "initials": "A"}, {"family": "Gad", "given": "Helge", "initials": "H", "orcid": "0000-0001-6530-1443", "researcher": {"href": "https://publications.scilifelab.se/researcher/6273ef3dd1574185af0a83e9ab31bfe5.json"}}, {"family": "Wiita", "given": "Elisee", "initials": "E"}, {"family": "G\u00f6kt\u00fcrk", "given": "Camilla", "initials": "C", "orcid": "0000-0002-6272-9927", "researcher": {"href": "https://publications.scilifelab.se/researcher/9318cec5020f4c92b8393b20242c0d58.json"}}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Friedrich", "given": "Stefanie", "initials": "S", "orcid": "0000-0002-3889-5589", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e1de4177ae649aba93a633ca451ebdb.json"}}, {"family": "Centio", "given": "Anders", "initials": "A"}, {"family": "Estruch", "given": "Montserrat", "initials": "M", "orcid": "0000-0002-7162-4158", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf0c60406fc74282b87f74170571d297.json"}}, {"family": "V\u00e5tsveen", "given": "Thea Kristin", "initials": "TK"}, {"family": "Struyf", "given": "Nona", "initials": "N", "orcid": "0000-0002-6975-0753", "researcher": {"href": "https://publications.scilifelab.se/researcher/1295c3be31024c4fa2da10cffe42c406.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Wallner", "given": "Olov", "initials": "O"}, {"family": "Sandvall", "given": "Teresa", "initials": "T"}, {"family": "Lehmann", "given": "S\u00f6ren", "initials": "S"}, {"family": "Theilgaard-M\u00f6nch", "given": "Kim", "initials": "K", "orcid": "0000-0002-4239-4939", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ac2392d2c784203b15e8ec53d6a746e.json"}}, {"family": "Garnett", "given": "Mathew J", "initials": "MJ", "orcid": "0000-0002-2618-4237", "researcher": {"href": "https://publications.scilifelab.se/researcher/81268f585935408e9a9673db9da394f6.json"}}, {"family": "\u00d6stling", "given": "P\u00e4ivi", "initials": "P"}, {"family": "Walfridsson", "given": "Julian", "initials": "J"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications.scilifelab.se/researcher/a74c79d4b11346a4918f536b5a678e12.json"}}], "type": "journal article", "published": "2021-11-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "81", "issue": "22", "pages": "5733-5744", "issn-l": "0008-5472"}, "abstract": "Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, exhibiting high levels of reactive oxygen species (ROS). ROS levels have been suggested to drive leukemogenesis and is thus a potential novel target for treating AML. MTH1 prevents incorporation of oxidized nucleotides into the DNA to maintain genome integrity and is upregulated in many cancers. Here we demonstrate that hematologic cancers are highly sensitive to MTH1 inhibitor TH1579 (karonudib). A functional precision medicine ex vivo screen in primary AML bone marrow samples demonstrated a broad response profile of TH1579, independent of the genomic alteration of AML, resembling the response profile of the standard-of-care treatments cytarabine and doxorubicin. Furthermore, TH1579 killed primary human AML blast cells (CD45+) as well as chemotherapy resistance leukemic stem cells (CD45+Lin-CD34+CD38-), which are often responsible for AML progression. TH1579 killed AML cells by causing mitotic arrest, elevating intracellular ROS levels, and enhancing oxidative DNA damage. TH1579 showed a significant therapeutic window, was well tolerated in animals, and could be combined with standard-of-care treatments to further improve efficacy. TH1579 significantly improved survival in two different AML disease models in vivo. In conclusion, the preclinical data presented here support that TH1579 is a promising novel anticancer agent for AML, providing a rationale to investigate the clinical usefulness of TH1579 in AML in an ongoing clinical phase I trial. SIGNIFICANCE: The MTH1 inhibitor TH1579 is a potential novel AML treatment, targeting both blasts and the pivotal leukemic stem cells while sparing normal bone marrow cells.", "doi": "10.1158/0008-5472.CAN-21-0061", "pmid": "34593524", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9397639"}, {"db": "pii", "key": "0008-5472.CAN-21-0061"}], "notes": [], "created": "2023-11-27T21:58:04.269Z", "modified": "2024-01-16T13:48:38.121Z"}, {"entity": "publication", "iuid": "3d52c9ab12914a419feae20a6e446826", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3d52c9ab12914a419feae20a6e446826.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3d52c9ab12914a419feae20a6e446826"}}, "title": "Thermal Proteome Profiling Identifies Oxidative-Dependent Inhibition of the Transcription of Major Oncogenes as a New Therapeutic Mechanism for Select Anticancer Compounds.", "authors": [{"family": "Peuget", "given": "Sylvain", "initials": "S"}, {"family": "Zhu", "given": "Jiawei", "initials": "J"}, {"family": "Sanz", "given": "Gema", "initials": "G", "orcid": "0000-0002-6227-0431", "researcher": {"href": "https://publications.scilifelab.se/researcher/3353dc98689341b4824217786d1e3956.json"}}, {"family": "Singh", "given": "Madhurendra", "initials": "M"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Chen", "given": "Xinsong", "initials": "X"}, {"family": "Shi", "given": "Yao", "initials": "Y"}, {"family": "Saei", "given": "Amir Ata", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}}, {"family": "Lindstr\u00f6m", "given": "Mikael S", "initials": "MS", "orcid": "0000-0003-1148-8497", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aa942fbfbee4257a129b3e7888f5b6d.json"}}, {"family": "Rihani", "given": "Ali", "initials": "A", "orcid": "0000-0002-6176-0519", "researcher": {"href": "https://publications.scilifelab.se/researcher/5dc94d95e8204181bf3e75354ec1678b.json"}}, {"family": "Moyano-Galceran", "given": "Lidia", "initials": "L", "orcid": "0000-0001-9219-6394", "researcher": {"href": "https://publications.scilifelab.se/researcher/085eed2a15bc4be08acbe21a18cb4e6c.json"}}, {"family": "Carlson", "given": "Joseph W", "initials": "JW", "orcid": "0000-0002-3006-4107", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb81cad4b24d4692bc21bda7305f21f1.json"}}, {"family": "Hjerpe", "given": "Elisabet", "initials": "E"}, {"family": "Joneborg", "given": "Ulrika", "initials": "U"}, {"family": "Lehti", "given": "Kaisa", "initials": "K", "orcid": "0000-0001-9110-8719", "researcher": {"href": "https://publications.scilifelab.se/researcher/480c0e2b92df4dccbae3940721525345.json"}}, {"family": "Hartman", "given": "Johan", "initials": "J", "orcid": "0000-0002-6500-8527", "researcher": {"href": "https://publications.scilifelab.se/researcher/da7cefda6e00463d8ba95fc63eeb8f0a.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Zubarev", "given": "Roman", "initials": "R", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Selivanova", "given": "Galina", "initials": "G"}], "type": "journal article", "published": "2020-04-01", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "issn-l": "0008-5472", "volume": "80", "issue": "7", "pages": "1538-1550"}, "abstract": "Identification of the molecular mechanism of action (MoA) of bioactive compounds is a crucial step for drug development but remains a challenging task despite recent advances in technology. In this study, we applied multidimensional proteomics, sensitivity correlation analysis, and transcriptomics to identify a common MoA for the anticancer compounds RITA, aminoflavone (AF), and oncrasin-1 (Onc-1). Global thermal proteome profiling revealed that the three compounds target mRNA processing and transcription, thereby attacking a cancer vulnerability, transcriptional addiction. This led to the preferential loss of expression of oncogenes involved in PDGF, EGFR, VEGF, insulin/IGF/MAPKK, FGF, Hedgehog, TGF\u03b2, and PI3K signaling pathways. Increased reactive oxygen species level in cancer cells was a prerequisite for targeting the mRNA transcription machinery, thus conferring cancer selectivity to these compounds. Furthermore, DNA repair factors involved in homologous recombination were among the most prominently repressed proteins. In cancer patient samples, RITA, AF, and Onc-1 sensitized to poly(ADP-ribose) polymerase inhibitors both in vitro and ex vivo These findings might pave a way for new synthetic lethal combination therapies.Significance: These findings highlight agents that target transcriptional addiction in cancer cells and suggest combination treatments that target RNA processing and DNA repair pathways simultaneously as effective cancer therapies.", "doi": "10.1158/0008-5472.CAN-19-2069", "pmid": "32019870", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-19-2069"}], "notes": [], "created": "2020-02-07T22:52:26.989Z", "modified": "2024-01-18T23:48:25.871Z"}, {"entity": "publication", "iuid": "a8a03bd63d704bc499a3bc17628952bd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a8a03bd63d704bc499a3bc17628952bd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a8a03bd63d704bc499a3bc17628952bd"}}, "title": "Computational and Experimental Druggability Assessment of Human DNA Glycosylases.", "authors": [{"family": "Michel", "given": "Maurice", "initials": "M", "orcid": "0000-0003-3261-2493", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f7cb5d695254481b745f86a824ac1b5.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Seashore-Ludlow", "given": "Brinton", "initials": "B"}, {"family": "Hedenstr\u00f6m", "given": "Mattias", "initials": "M"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Vallin", "given": "Karl", "initials": "K"}, {"family": "Paulin", "given": "Cynthia B J", "initials": "CBJ"}, {"family": "Zhang", "given": "Jiaxi", "initials": "J"}, {"family": "Wallner", "given": "Olov", "initials": "O"}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Schmidt", "given": "Andreas", "initials": "A"}, {"family": "Jenmalm-Jensen", "given": "Annika", "initials": "A"}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2019-07-31", "journal": {"volume": "4", "issn": "2470-1343", "issue": "7", "pages": "11642-11656", "title": "ACS Omega", "issn-l": "2470-1343"}, "abstract": "Due to a polar or even charged binding interface, DNA-binding proteins are considered extraordinarily difficult targets for development of small-molecule ligands and only a handful of proteins have been targeted successfully to date. Recently, however, it has been shown that development of selective and efficient inhibitors of 8-oxoguanine DNA glycosylase is possible. Here, we describe the initial druggability assessment of DNA glycosylases in a computational setting and experimentally investigate several methods to target endonuclease VIII-like 1 (NEIL1) with small-molecule inhibitors. We find that DNA glycosylases exhibit good predicted druggability in both DNA-bound and -unbound states. Furthermore, we find catalytic sites to be highly flexible, allowing for a range of interactions and binding partners. One flexible catalytic site was rationalized for NEIL1 and further investigated experimentally using both a biochemical assay in the presence of DNA and a thermal shift assay in the absence of DNA.", "doi": "10.1021/acsomega.9b00162", "pmid": "31460271", "labels": {"Swedish NMR Centre": "Collaborative", "Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC6682003"}], "notes": [], "created": "2019-11-22T14:28:02.268Z", "modified": "2025-10-17T13:04:28.547Z"}, {"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"}]}