{"entity": "researcher", "timestamp": "2026-06-08T05:44:18.656Z", "family": "Wannberg", "given": "Johan", "initials": "J", "orcid": "0000-0001-5494-0848", "affiliations": ["SciLifeLab Drug Discovery & Development Platform, Medicinal Chemistry - Lead Identification, Department of Medicinal Chemistry; Uppsala University; SE-751 23 Uppsala SWEDEN"], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/d093f5fb52f644ce8994f3a6308272a8.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/d093f5fb52f644ce8994f3a6308272a8"}}, "publications": [{"entity": "publication", "iuid": "483fd25be0c940a88ec33ee37fd176c8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/483fd25be0c940a88ec33ee37fd176c8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/483fd25be0c940a88ec33ee37fd176c8"}}, "title": "Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress.", "authors": [{"family": "Bonagas", "given": "Nadilly", "initials": "N", "orcid": "0000-0001-7336-4065", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e38f3b0752740969c5c13fb77885b27.json"}}, {"family": "Gustafsson", "given": "Nina M S", "initials": "NMS"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e3e92bdf843456784f98d3b521d2ccd.json"}}, {"family": "Gustafsson", "given": "Robert", "initials": "R", "orcid": "0000-0002-4854-5531", "researcher": {"href": "https://publications.scilifelab.se/researcher/16dd7e73adad4f85972d1d546bfa6d2a.json"}}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Borhade", "given": "Sanjay", "initials": "S"}, {"family": "Green", "given": "Alanna C", "initials": "AC"}, {"family": "Vallin", "given": "Karl S A", "initials": "KSA"}, {"family": "Sarno", "given": "Antonio", "initials": "A"}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "G\u00f6kt\u00fcrk", "given": "Camilla", "initials": "C"}, {"family": "Pham", "given": "Therese", "initials": "T"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Cookson", "given": "Victoria", "initials": "V", "orcid": "0000-0003-3089-4837", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cd81b473de74c26bad811b3c2f25b7f.json"}}, {"family": "Kiweler", "given": "Nicole", "initials": "N", "orcid": "0000-0001-7493-703X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8b0eaee2d574b4daba1ee735c512797.json"}}, {"family": "Sandberg", "given": "Lars", "initials": "L"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Unterlass", "given": "Judith E", "initials": "JE"}, {"family": "Haraldsson", "given": "Martin", "initials": "M"}, {"family": "Andersson", "given": "Yasmin", "initials": "Y"}, {"family": "Scaletti", "given": "Emma R", "initials": "ER"}, {"family": "Bengtsson", "given": "Christoffer", "initials": "C"}, {"family": "Paulin", "given": "Cynthia B J", "initials": "CBJ"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Abdurakhmanov", "given": "Eldar", "initials": "E"}, {"family": "Pudelko", "given": "Linda", "initials": "L"}, {"family": "Kunz", "given": "Ben", "initials": "B"}, {"family": "Desroses", "given": "Matthieu", "initials": "M"}, {"family": "Iliev", "given": "Petar", "initials": "P"}, {"family": "F\u00e4rneg\u00e5rdh", "given": "Katarina", "initials": "K"}, {"family": "Kr\u00e4mer", "given": "Andreas", "initials": "A", "orcid": "0000-0003-3294-2660", "researcher": {"href": "https://publications.scilifelab.se/researcher/37f158e9b24d43b69753ccbf029cb793.json"}}, {"family": "Garg", "given": "Neeraj", "initials": "N"}, {"family": "Michel", "given": "Maurice", "initials": "M"}, {"family": "H\u00e4ggblad", "given": "Sara", "initials": "S"}, {"family": "Jarvius", "given": "Malin", "initials": "M"}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C"}, {"family": "Jensen", "given": "Amanda B\u00f6gedahl", "initials": "AB"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Karsten", "given": "Stella", "initials": "S", "orcid": "0000-0001-6191-4314", "researcher": {"href": "https://publications.scilifelab.se/researcher/4cbde9247c7145ff8ea0bbc0b0c5c477.json"}}, {"family": "Zhang", "given": "Si Min", "initials": "SM"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Eriksson", "given": "Anders", "initials": "A"}, {"family": "Liu", "given": "Jianping", "initials": "J", "orcid": "0000-0002-7336-3895", "researcher": {"href": "https://publications.scilifelab.se/researcher/e77624d9d5b841608e142afbe2ead1d7.json"}}, {"family": "Glinghammar", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Nekhotiaeva", "given": "Natalia", "initials": "N"}, {"family": "Klingeg\u00e5rd", "given": "Fredrik", "initials": "F"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Martens", "given": "Ulf", "initials": "U"}, {"family": "Llona-Minguez", "given": "Sabin", "initials": "S"}, {"family": "Moulson", "given": "Ruth", "initials": "R"}, {"family": "Nordstr\u00f6m", "given": "Helena", "initials": "H"}, {"family": "Parrow", "given": "Vendela", "initials": "V"}, {"family": "Dahllund", "given": "Leif", "initials": "L"}, {"family": "Sj\u00f6berg", "given": "Birger", "initials": "B"}, {"family": "Vargas", "given": "Irene L", "initials": "IL"}, {"family": "Vo", "given": "Duy Duc", "initials": "DD"}, {"family": "Wannberg", "given": "Johan", "initials": "J", "orcid": "0000-0001-5494-0848", "researcher": {"href": "https://publications.scilifelab.se/researcher/d093f5fb52f644ce8994f3a6308272a8.json"}}, {"family": "Knapp", "given": "Stefan", "initials": "S", "orcid": "0000-0001-5995-6494", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4d84c40612d48f280d4ead25558d835.json"}}, {"family": "Krokan", "given": "Hans E", "initials": "HE"}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Meiser", "given": "Johannes", "initials": "J"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW"}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "Nat Cancer", "issn": "2662-1347", "volume": "3", "issue": "2", "pages": "156-172", "issn-l": null}, "abstract": "The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors.", "doi": "10.1038/s43018-022-00331-y", "pmid": "35228749", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s43018-022-00331-y"}, {"db": "pmc", "key": "PMC8885417"}], "notes": [], "created": "2022-05-07T05:35:33.240Z", "modified": "2025-10-17T13:05:07.816Z"}, {"entity": "publication", "iuid": "8a54abdac0304e9eb0f0b3862fe27c80", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8a54abdac0304e9eb0f0b3862fe27c80.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8a54abdac0304e9eb0f0b3862fe27c80"}}, "title": "A Series of Analogues to the AT 2R Prototype Antagonist C38 Allow Fine Tuning of the Previously Reported Antagonist Binding Mode.", "authors": [{"family": "Isaksson", "given": "Rebecka", "initials": "R", "orcid": "0000-0002-6389-5046", "researcher": {"href": "https://publications.scilifelab.se/researcher/ecad4139af504c3aa65ac86c65de28bc.json"}}, {"family": "Lindman", "given": "Jens", "initials": "J", "orcid": "0000-0003-4795-6117", "researcher": {"href": "https://publications.scilifelab.se/researcher/595f3ad3a575491a95c76672c629c64b.json"}}, {"family": "Wannberg", "given": "Johan", "initials": "J", "orcid": "0000-0001-5494-0848", "researcher": {"href": "https://publications.scilifelab.se/researcher/d093f5fb52f644ce8994f3a6308272a8.json"}}, {"family": "Sallander", "given": "Jessica", "initials": "J", "orcid": "0000-0002-0408-5289", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac374a149df9468d892e37bc11147a68.json"}}, {"family": "Backlund", "given": "Maria", "initials": "M", "orcid": "0000-0002-6253-816X", "researcher": {"href": "https://publications.scilifelab.se/researcher/bffc6d0b93b64dafa4c17abf7910964e.json"}}, {"family": "Baraldi", "given": "Dhaniel", "initials": "D", "orcid": "0000-0002-9688-4183", "researcher": {"href": "https://publications.scilifelab.se/researcher/226a2b7a6920494994ae795b95cf9381.json"}}, {"family": "Widdop", "given": "Robert", "initials": "R", "orcid": "0000-0002-6515-0435", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a1c0488523f42ac9246798135cb57dd.json"}}, {"family": "Hallberg", "given": "Mathias", "initials": "M", "orcid": "0000-0002-9835-870X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6450e1c0206e41ec9aa59866bb529766.json"}}, {"family": "\u00c5qvist", "given": "Johan", "initials": "J", "orcid": "0000-0003-2091-0610", "researcher": {"href": "https://publications.scilifelab.se/researcher/9777a1c6e1bd4181bc46dce4be3c2146.json"}}, {"family": "Gutierrez de Teran", "given": "Hugo", "initials": "H", "orcid": "0000-0003-0459-3491", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2c1a83f44474224b4788bfcbfcd1a43.json"}}, {"family": "Gising", "given": "Johan", "initials": "J", "orcid": "0000-0001-8852-6071", "researcher": {"href": "https://publications.scilifelab.se/researcher/558a444faff84f108251e7521870ec2b.json"}}, {"family": "Larhed", "given": "Mats", "initials": "M", "orcid": "0000-0001-6258-0635", "researcher": {"href": "https://publications.scilifelab.se/researcher/011ee4a03a534099a5d71b0fdd6dbe81.json"}}], "type": "journal article", "published": "2019-01-00", "journal": {"volume": "8", "issn": "2191-1363", "issue": "1", "pages": "114-125", "title": "ChemistryOpen", "issn-l": "2191-1363"}, "abstract": "We here report on our continued studies of ligands binding to the promising drug target angiotensin II type 2 receptor (AT 2R). Two series of compounds were synthesized and investigated. The first series explored the effects of adding small substituents to the phenyl ring of the known selective nonpeptide AT2R antagonist C38, generating small but significant shifts in AT2R affinity. One compound in the first series was equipotent to C38 and showed similar kinetic solubility, and stability in both human and mouse liver microsomes. The second series was comprised of new bicyclic derivatives, amongst which one ligand exhibited a five-fold improved affinity to AT2R as compared to C38. The majority of the compounds in the second series, including the most potent ligand, were inferior to C38 with regard to stability in both human and mouse microsomes. In contrast to our previously reported findings, ligands with shorter carbamate alkyl chains only demonstrated slightly improved stability in microsomes. Based on data presented herein, a more adequate, tentative model of the binding modes of ligand analogues to the prototype AT2R antagonist C38 is proposed, as deduced from docking redefined by molecular dynamic simulations.", "doi": "10.1002/open.201800282", "pmid": "30697513", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "OPEN201800282"}, {"db": "pmc", "key": "PMC6346239"}], "notes": [], "created": "2019-11-13T16:02:37.348Z", "modified": "2025-10-17T13:05:08.282Z"}]}