{"entity": "researcher", "timestamp": "2026-08-23T09:27:18.744Z", "family": "Fuchs", "given": "Natalie", "initials": "N", "orcid": "0000-0001-6404-676X", "affiliations": ["Department of Radiology, Molecular Imaging Innovations Institute (MI3), Weill Cornell Medicine, New York, New York 10065, United States."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/7b6361026fb346eb9492cfa9e6ccc6c3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/7b6361026fb346eb9492cfa9e6ccc6c3"}}, "publications": [{"entity": "publication", "iuid": "076d6110c3534827b899996c31b56c57", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/076d6110c3534827b899996c31b56c57.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/076d6110c3534827b899996c31b56c57"}}, "title": "From Virtual Screens to Cellular Target Engagement: New Small Molecule Ligands for the Immune Checkpoint LAG-3.", "authors": [{"family": "Fuchs", "given": "Natalie", "initials": "N", "orcid": "0000-0001-6404-676X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7b6361026fb346eb9492cfa9e6ccc6c3.json"}}, {"family": "Calvo-Barreiro", "given": "Laura", "initials": "L"}, {"family": "Talagayev", "given": "Valerij", "initials": "V"}, {"family": "Pach", "given": "Szymon", "initials": "S"}, {"family": "Wolber", "given": "Gerhard", "initials": "G", "orcid": "0000-0002-5344-0048", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dbe8bad6f5d848169211aec92819afdb.json"}}, {"family": "Gabr", "given": "Moustafa T", "initials": "MT", "orcid": "0000-0001-9074-3331", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d3a210849647418bad02981dfeddf861.json"}}], "type": "journal article", "published": "2024-11-14", "journal": {"title": "ACS Med. Chem. Lett.", "issn": "1948-5875", "volume": "15", "issue": "11", "pages": "1884-1890", "issn-l": "1948-5875"}, "abstract": "Herein, we performed a virtual screening study to discover new scaffolds for small molecule-based ligands of the immune checkpoint lymphocyte-activation gene 3 (LAG-3). Molecular dynamics (MD) simulations using the LAG-3 structure revealed two putative binding sites for small molecules: the antibody interface and the lipophilic canyon. A 3D pharmacophore screening resulted in the identification of potential ligands for these binding sites and afforded a library of 25 compounds. We then evaluated the screening hits for LAG-3 binding via microscale thermophoresis (MST) and surface plasmon resonance (SPR). Our biophysical screening identified two binders with K D values in the low micromolar range, compounds 3 (antibody interface) and 25 (lipophilic canyon). Furthermore, we investigated the ability of LAG-3 hits to engage LAG-3 on a cellular level using a cellular thermal shift assay (CETSA). In summary, compound 3 shows potential as a lead but is not yet a development candidate.", "doi": "10.1021/acsmedchemlett.4c00350", "pmid": "39563794", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11571005"}], "notes": [], "created": "2026-08-21T11:36:30.043Z", "modified": "2026-08-21T11:36:30.191Z"}]}