{"entity": "publication", "iuid": "a85985f876bf44cf917c583351815d1a", "timestamp": "2026-09-28T11:19:30.376Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a85985f876bf44cf917c583351815d1a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a85985f876bf44cf917c583351815d1a"}}, "title": "Computational and Experimental Druggability Assessment of Human DNA Glycosylases.", "authors": [{"family": "Michel", "given": "Maurice", "initials": "M"}, {"family": "Visnes", "given": "Torkild", "initials": "T"}, {"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"}], "type": "journal article", "published": "2019-07-31", "journal": {"title": "ACS Omega", "issn": "2470-1343", "volume": "4", "issue": "7", "pages": "11642-11656", "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": [], "xrefs": [{"db": "pmc", "key": "PMC6682003"}], "notes": [], "created": "2026-09-23T10:05:14.350Z", "modified": "2026-09-23T10:43:53.589Z"}