{"entity": "researcher", "timestamp": "2026-06-15T17:56:36.216Z", "family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "affiliations": ["Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/1eac01c3a53d4940ade49b24f13dd214.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/1eac01c3a53d4940ade49b24f13dd214"}}, "publications": [{"entity": "publication", "iuid": "6befcd3ead5a4b38aa1ed2b2a3efb705", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6befcd3ead5a4b38aa1ed2b2a3efb705.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6befcd3ead5a4b38aa1ed2b2a3efb705"}}, "title": "Coupling cellular drug-target engagement to downstream pharmacology with CeTEAM.", "authors": [{"family": "Valerie", "given": "Nicholas C K", "initials": "NCK", "orcid": "0000-0002-9423-964X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1d90c5a1f924c8b97409934dec74b0b.json"}}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications.scilifelab.se/researcher/b62a88fc39a54906a40e28e679c9f624.json"}}, {"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1eac01c3a53d4940ade49b24f13dd214.json"}}, {"family": "Alam", "given": "Seher", "initials": "S"}, {"family": "Pires", "given": "Maria J", "initials": "MJ"}, {"family": "Stigsdotter", "given": "Hannah", "initials": "H"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Langelier", "given": "Marie-France", "initials": "MF", "orcid": "0000-0001-9815-1840", "researcher": {"href": "https://publications.scilifelab.se/researcher/caac2647bbde41dbbd7d5fd31fb2da70.json"}}, {"family": "Rehling", "given": "Daniel", "initials": "D"}, {"family": "Throup", "given": "Adam", "initials": "A", "orcid": "0000-0001-6512-8679", "researcher": {"href": "https://publications.scilifelab.se/researcher/dea6b870fafa471499bd71f1b2693be4.json"}}, {"family": "Purewal-Sidhu", "given": "Oryn", "initials": "O"}, {"family": "Desroses", "given": "Matthieu", "initials": "M"}, {"family": "Onireti", "given": "Jacob", "initials": "J", "orcid": "0009-0003-9745-4446", "researcher": {"href": "https://publications.scilifelab.se/researcher/989eece269e544728082d7764d924d52.json"}}, {"family": "Wakchaure", "given": "Prasad", "initials": "P"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Bostr\u00f6m", "given": "Johan", "initials": "J"}, {"family": "Bevc", "given": "Luka", "initials": "L"}, {"family": "Benzi", "given": "Giorgia", "initials": "G"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "Pascal", "given": "John M", "initials": "JM", "orcid": "0000-0002-2714-4317", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee603b6cd7984898bd6cdbb601e4b3e7.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Page", "given": "Brent D G", "initials": "BDG"}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications.scilifelab.se/researcher/4317b773615e476694840e907b7b1a0c.json"}}], "type": "journal article", "published": "2024-12-06", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "10347", "issn-l": "2041-1723"}, "abstract": "Cellular target engagement technologies enable quantification of intracellular drug binding; however, simultaneous assessment of drug-associated phenotypes has proven challenging. Here, we present cellular target engagement by accumulation of mutant as a platform that can concomitantly evaluate drug-target interactions and phenotypic responses using conditionally stabilized drug biosensors. We observe that drug-responsive proteotypes are prevalent among reported mutants of known drug targets. Compatible mutants appear to follow structural and biophysical logic that permits intra-protein and paralogous expansion of the biosensor pool. We then apply our method to uncouple target engagement from divergent cellular activities of MutT homolog 1 (MTH1) inhibitors, dissect Nudix hydrolase 15 (NUDT15)-associated thiopurine metabolism with the R139C pharmacogenetic variant, and profile the dynamics of poly(ADP-ribose) polymerase 1/2 (PARP1/2) binding and DNA trapping by PARP inhibitors (PARPi). Further, PARP1-derived biosensors facilitated high-throughput screening for PARP1 binders, as well as multimodal ex vivo analysis and non-invasive tracking of PARPi binding in live animals. This approach can facilitate holistic assessment of drug-target engagement by bridging drug binding events and their biological consequences.", "doi": "10.1038/s41467-024-54415-7", "pmid": "39643609", "labels": {"Chemical Biology Consortium Sweden": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11624193"}, {"db": "pii", "key": "10.1038/s41467-024-54415-7"}], "notes": [], "created": "2024-12-16T08:43:06.953Z", "modified": "2025-10-17T13:04:27.012Z"}, {"entity": "publication", "iuid": "15722bb1086f44f7bd700d32703ab2a9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/15722bb1086f44f7bd700d32703ab2a9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/15722bb1086f44f7bd700d32703ab2a9"}}, "title": "Identification and evaluation of small-molecule inhibitors against the dNTPase SAMHD1viaa comprehensive screening funnel", "authors": [{"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1eac01c3a53d4940ade49b24f13dd214.json"}}, {"family": "Paulin", "given": "Cynthia B J", "initials": "CBJ", "orcid": "0000-0002-5698-7962", "researcher": {"href": "https://publications.scilifelab.se/researcher/f54dd3938c0640f1b770a3b52baba6d9.json"}}, {"family": "Michel", "given": "Maurice", "initials": "M", "orcid": "0000-0003-3261-2493", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f7cb5d695254481b745f86a824ac1b5.json"}}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e3e92bdf843456784f98d3b521d2ccd.json"}}, {"family": "Yag\u00fce-Capilla", "given": "Miriam", "initials": "M"}, {"family": "Bwanika", "given": "Henri Colyn", "initials": "HC"}, {"family": "Shu", "given": "Huazhang", "initials": "H"}, {"family": "Vekatram", "given": "Rajagopal Papagudi", "initials": "RP"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Jemth", "given": "Ann Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Ortis", "given": "Florian", "initials": "F"}, {"family": "Dirks", "given": "Christopher", "initials": "C", "orcid": "0000-0003-4503-8291", "researcher": {"href": "https://publications.scilifelab.se/researcher/2188fde32a784feaa40cfff1e18c1125.json"}}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Linde", "given": "Erika", "initials": "E"}, {"family": "Lee", "given": "Sun", "initials": "S"}, {"family": "Llona-Minguez", "given": "Sabin", "initials": "S", "orcid": "0000-0003-3187-722X", "researcher": {"href": "https://publications.scilifelab.se/researcher/437b1f98ad21471f884226ed89a3da12.json"}}, {"family": "Haraldsson", "given": "Martin", "initials": "M", "orcid": "0000-0003-0743-7830", "researcher": {"href": "https://publications.scilifelab.se/researcher/42031e3e48ba47f896b74bfb733cdeff.json"}}, {"family": "Str\u00f6mberg", "given": "Kia", "initials": "K"}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Scobie", "given": "Martin", "initials": "M", "orcid": "0000-0002-7073-8495", "researcher": {"href": "https://publications.scilifelab.se/researcher/87c041a8b3414f5db02873dc8013806b.json"}}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T", "orcid": "0000-0002-8145-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/e13df787cb884549bcf333aba4e6f010.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf1e23d9748e4868a4b5e966e423b1a9.json"}}], "type": "posted-content", "published": "2023-01-18", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2023.01.17.524275", "pmid": null, "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-10-18T18:41:03.768Z", "modified": "2025-12-18T19:56:49.749Z"}, {"entity": "publication", "iuid": "08a45a5b61b8441ea51d9b53a518fc25", "links": {"self": {"href": "https://publications.scilifelab.se/publication/08a45a5b61b8441ea51d9b53a518fc25.json"}, "display": {"href": "https://publications.scilifelab.se/publication/08a45a5b61b8441ea51d9b53a518fc25"}}, "title": "Development of a chemical probe against NUDT15.", "authors": [{"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1eac01c3a53d4940ade49b24f13dd214.json"}}, {"family": "Desroses", "given": "Matthieu", "initials": "M", "orcid": "0000-0003-4152-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/b232b70751004e9ea6b547533f901376.json"}}, {"family": "Hagenkort", "given": "Anna", "initials": "A"}, {"family": "Valerie", "given": "Nicholas C K", "initials": "NCK"}, {"family": "Rehling", "given": "Daniel", "initials": "D", "orcid": "0000-0002-8627-3469", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4d521579d594e44b783a8d2e9fb98bb.json"}}, {"family": "Carter", "given": "Megan", "initials": "M"}, {"family": "Wallner", "given": "Olov", "initials": "O"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Throup", "given": "Adam", "initials": "A"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T", "orcid": "0000-0002-8145-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/e13df787cb884549bcf333aba4e6f010.json"}}, {"family": "Axelsson", "given": "Hanna", "initials": "H", "orcid": "0000-0003-2365-1749", "researcher": {"href": "https://publications.scilifelab.se/researcher/63b88c4d11c443f39121c6d93fcff1f0.json"}}, {"family": "Regmi", "given": "Shruti", "initials": "S"}, {"family": "Sarno", "given": "Antonio", "initials": "A"}, {"family": "Kr\u00e4mer", "given": "Andreas", "initials": "A"}, {"family": "Pudelko", "given": "Linda", "initials": "L"}, {"family": "Br\u00e4utigam", "given": "Lars", "initials": "L"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "G\u00f6ttmann", "given": "Mona", "initials": "M"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Kutzner", "given": "Juliane", "initials": "J"}, {"family": "Schaller", "given": "Torsten", "initials": "T", "orcid": "0000-0001-9597-4112", "researcher": {"href": "https://publications.scilifelab.se/researcher/c74944db1b4f4fe4a09079f417f8eec6.json"}}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C"}, {"family": "C\u00e1zares-K\u00f6rner", "given": "Armando", "initials": "A"}, {"family": "Page", "given": "Brent D G", "initials": "BDG"}, {"family": "Krimpenfort", "given": "Rosa", "initials": "R"}, {"family": "Eshtad", "given": "Saeed", "initials": "S", "orcid": "0000-0001-6763-4700", "researcher": {"href": "https://publications.scilifelab.se/researcher/edf4a705cae045feb64d1d9c7f8d9646.json"}}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications.scilifelab.se/researcher/4317b773615e476694840e907b7b1a0c.json"}}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf1e23d9748e4868a4b5e966e423b1a9.json"}}, {"family": "Knapp", "given": "Stefan", "initials": "S", "orcid": "0000-0001-5995-6494", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4d84c40612d48f280d4ead25558d835.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications.scilifelab.se/researcher/a74c79d4b11346a4918f536b5a678e12.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Nat. Chem. Biol.", "issn": "1552-4469", "volume": "16", "issue": "10", "pages": "1120-1128", "issn-l": "1552-4450"}, "abstract": "The NUDIX hydrolase NUDT15 was originally implicated in sanitizing oxidized nucleotides, but was later shown to hydrolyze the active thiopurine metabolites, 6-thio-(d)GTP, thereby dictating the clinical response of this standard-of-care treatment for leukemia and inflammatory diseases. Nonetheless, its physiological roles remain elusive. Here, we sought to develop small-molecule NUDT15 inhibitors to elucidate its biological functions and potentially to improve NUDT15-dependent chemotherapeutics. Lead compound TH1760 demonstrated low-nanomolar biochemical potency through direct and specific binding into the NUDT15 catalytic pocket and engaged cellular NUDT15 in the low-micromolar range. We also employed thiopurine potentiation as a proxy functional readout and demonstrated that TH1760 sensitized cells to 6-thioguanine through enhanced accumulation of 6-thio-(d)GTP in nucleic acids. A biochemically validated, inactive structural analog, TH7285, confirmed that increased thiopurine toxicity takes place via direct NUDT15 inhibition. In conclusion, TH1760 represents the first chemical probe for interrogating NUDT15 biology and potential therapeutic avenues.", "doi": "10.1038/s41589-020-0592-z", "pmid": "32690945", "labels": {"Protein Science Facility (PSF)": "Service", "Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41589-020-0592-z"}, {"db": "pmc", "key": "PMC7610571"}, {"db": "mid", "key": "EMS118347"}], "notes": [], "created": "2020-09-25T11:44:11.217Z", "modified": "2025-10-17T13:04:28.262Z"}]}