{"entity": "researcher", "timestamp": "2026-08-20T21:26:44.690Z", "family": "Elkins", "given": "Jonathan M", "initials": "JM", "orcid": "0000-0003-2858-8929", "affiliations": ["Centro de Qu\u00edmica Medicinal, Centro de Biologia Molecular e Engenharia Gen\u00e9tica, Universidade Estadual de Campinas, Av. Dr. Andr\u00e9 Tosello 550, 13083-886 Campinas, S\u00e3o Paulo Brazil."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/3492a1a5a1ec490d955b2de5c25bb078.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/3492a1a5a1ec490d955b2de5c25bb078"}}, "publications": [{"entity": "publication", "iuid": "a4889998c3fa4142848b905506cdd527", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a4889998c3fa4142848b905506cdd527.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a4889998c3fa4142848b905506cdd527"}}, "title": "Novel Dihydropteridinone Derivatives As Potent Inhibitors of the Understudied Human Kinases Vaccinia-Related Kinase 1 and Casein Kinase 1\u03b4/\u03b5.", "authors": [{"family": "de Souza Gama", "given": "Fernando H", "initials": "FH"}, {"family": "Dutra", "given": "Luiz A", "initials": "LA", "orcid": "0000-0002-3316-8526", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/54947161b467412cb8b67ea2a9551b5a.json"}}, {"family": "Hawgood", "given": "Michael", "initials": "M", "orcid": "0000-0003-3886-7534", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4e5a4b28e7e84cd180fd293c1d46d12f.json"}}, {"family": "Dos Reis", "given": "Caio Vin\u00edcius", "initials": "CV"}, {"family": "Serafim", "given": "Ricardo A M", "initials": "RAM", "orcid": "0000-0003-0614-1798", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/05755073dbbb4a72b9ca9857b7af9ae2.json"}}, {"family": "Ferreira", "given": "Marcos A", "initials": "MA"}, {"family": "Teodoro", "given": "Bruno V M", "initials": "BVM"}, {"family": "Takarada", "given": "J\u00e9ssica Emi", "initials": "JE"}, {"family": "Santiago", "given": "Andr\u00e9 S", "initials": "AS", "orcid": "0000-0002-3973-3370", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e2451d0f47ae4e43a0798ff7b76a5f32.json"}}, {"family": "Balourdas", "given": "Dimitrios-Ilias", "initials": "DI", "orcid": "0000-0002-1790-2268", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bb44c08b0a624b8c827cfc52af368088.json"}}, {"family": "Nilsson", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Urien", "given": "Bruno", "initials": "B"}, {"family": "Almeida", "given": "Vitor M", "initials": "VM"}, {"family": "Gileadi", "given": "Carina", "initials": "C"}, {"family": "Ramos", "given": "Priscila Z", "initials": "PZ"}, {"family": "Salmazo", "given": "Anita", "initials": "A"}, {"family": "Vasconcelos", "given": "Stanley N S", "initials": "SNS"}, {"family": "Cunha", "given": "Micael R", "initials": "MR", "orcid": "0000-0001-5227-6816", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/af9b333b41c7428fb711f6810ce126a7.json"}}, {"family": "Mueller", "given": "Susanne", "initials": "S", "orcid": "0000-0003-2402-4157", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/02b49d33d342484a993527458dfacf6b.json"}}, {"family": "Knapp", "given": "Stefan", "initials": "S", "orcid": "0000-0001-5995-6494", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b6025ceada8d460aa28aa3175e423853.json"}}, {"family": "Massirer", "given": "Katlin B", "initials": "KB", "orcid": "0000-0001-6390-2560", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0998db7e84ee48099eab10c7301973cd.json"}}, {"family": "Elkins", "given": "Jonathan M", "initials": "JM", "orcid": "0000-0003-2858-8929", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3492a1a5a1ec490d955b2de5c25bb078.json"}}, {"family": "Gileadi", "given": "Opher", "initials": "O"}, {"family": "Mascarello", "given": "Alessandra", "initials": "A"}, {"family": "Lemmens", "given": "Bennie B L G", "initials": "BBLG", "orcid": "0000-0001-8051-1676", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e13fa5660a8d4b18a0ff3df3c263f78f.json"}}, {"family": "Guimar\u00e3es", "given": "Cristiano R W", "initials": "CRW"}, {"family": "Azevedo", "given": "Hatylas", "initials": "H", "orcid": "0000-0001-9233-0696", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a22c9763d02f4394b10fb9147048d864.json"}}, {"family": "Cou\u00f1ago", "given": "Rafael M", "initials": "RM", "orcid": "0000-0003-1847-5090", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3508b369daf74b4aa7ec63484b5cffae.json"}}], "type": "journal article", "published": "2024-06-13", "journal": {"title": "J Med Chem", "issn": "1520-4804", "volume": "67", "issue": "11", "pages": "8609-8629", "issn-l": "0022-2623"}, "abstract": "Vaccinia-related kinase 1 (VRK1) and the \u03b4 and \u03b5 isoforms of casein kinase 1 (CK1) are linked to various disease-relevant pathways. However, the lack of tool compounds for these kinases has significantly hampered our understanding of their cellular functions and therapeutic potential. Here, we describe the structure-based development of potent inhibitors of VRK1, a kinase highly expressed in various tumor types and crucial for cell proliferation and genome integrity. Kinome-wide profiling revealed that our compounds also inhibit CK1\u03b4 and CK1\u03b5. We demonstrate that dihydropteridinones 35 and 36 mimic the cellular outcomes of VRK1 depletion. Complementary studies with existing CK1\u03b4 and CK1\u03b5 inhibitors suggest that these kinases may play overlapping roles in cell proliferation and genome instability. Together, our findings highlight the potential of VRK1 inhibition in treating p53-deficient tumors and possibly enhancing the efficacy of existing cancer therapies that target DNA stability or cell division.", "doi": "10.1021/acs.jmedchem.3c02250", "pmid": "38780468", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T08:10:47.717Z", "modified": "2026-08-20T08:10:48.325Z"}]}