{"entity": "researcher", "timestamp": "2026-08-17T01:28:44.693Z", "family": "Busker", "given": "Sander", "initials": "S", "orcid": "0000-0002-7069-3864", "affiliations": ["Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solnav\u00e4gen 9, Biomedicum A3, Solna 171 65, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/78029e78072548688bf306c577738232.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/78029e78072548688bf306c577738232"}}, "publications": [{"entity": "publication", "iuid": "27f3b4d7ee294f0a881692c618690584", "links": {"self": {"href": "https://publications.scilifelab.se/publication/27f3b4d7ee294f0a881692c618690584.json"}, "display": {"href": "https://publications.scilifelab.se/publication/27f3b4d7ee294f0a881692c618690584"}}, "title": "Validating Signal Transducer and Activator of Transcription (STAT) Protein-Inhibitor Interactions Using Biochemical and Cellular Thermal Shift Assays.", "authors": [{"family": "Attarha", "given": "Sanaz", "initials": "S"}, {"family": "Reithmeier", "given": "Anja", "initials": "A"}, {"family": "Busker", "given": "Sander", "initials": "S", "orcid": "0000-0002-7069-3864", "researcher": {"href": "https://publications.scilifelab.se/researcher/78029e78072548688bf306c577738232.json"}}, {"family": "Desroses", "given": "Matthieu", "initials": "M", "orcid": "0000-0003-4152-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/b232b70751004e9ea6b547533f901376.json"}}, {"family": "Page", "given": "Brent D G", "initials": "BDG", "orcid": "0000-0002-2101-1329", "researcher": {"href": "https://publications.scilifelab.se/researcher/87dde8251a714d26b3b7cc045b47061f.json"}}], "type": "journal article", "published": "2020-07-17", "journal": {"volume": "15", "issn": "1554-8937", "issue": "7", "pages": "1842-1851", "title": "ACS Chem. Biol.", "issn-l": "1554-8929"}, "abstract": "Signal transducer and activator of transcription (STAT) proteins have important biological functions; however, deregulation of STAT signaling is a driving force behind the onset and progression of inflammatory diseases and cancer. While their biological roles suggest that STAT proteins would be valuable targets for developing therapeutic agents, STAT proteins are notoriously difficult to inhibit using small drug-like molecules, as they do not have a distinct inhibitor binding site. Despite this, a multitude of small-molecule STAT inhibitors have been proposed, primarily focusing on inhibiting STAT3 protein to generate novel cancer therapies. Demonstrating that inhibitors bind to their targets in cells has historically been a very challenging task. With the advent of modern target engagement techniques, such as the cellular thermal shift assay (CETSA), interactions between experimental compounds and their biological targets can be detected with relative ease. To investigate interactions between STAT proteins and inhibitors, we herein developed STAT CETSAs and evaluated known STAT3 inhibitors for their ability to engage STAT proteins in biological settings. While potent binding was detected between STAT proteins and peptidic STAT inhibitors, small-molecule inhibitors elicited variable responses, most of which failed to stabilize STAT3 proteins in cells and cell lysates. The described STAT thermal stability assays represent valuable tools for evaluating proposed STAT inhibitors.", "doi": "10.1021/acschembio.0c00046", "pmid": "32412740", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-06-02T11:24:45.376Z", "modified": "2025-10-17T13:04:28.276Z"}, {"entity": "publication", "iuid": "5f926bdd219e419880e434267d225d2d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5f926bdd219e419880e434267d225d2d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5f926bdd219e419880e434267d225d2d"}}, "title": "Irreversible TrxR1 inhibitors block STAT3 activity and induce cancer cell death.", "authors": [{"family": "Busker", "given": "S", "initials": "S", "orcid": "0000-0002-7069-3864", "researcher": {"href": "https://publications.scilifelab.se/researcher/78029e78072548688bf306c577738232.json"}}, {"family": "Qian", "given": "W", "initials": "W"}, {"family": "Haraldsson", "given": "M", "initials": "M"}, {"family": "Espinosa", "given": "B", "initials": "B"}, {"family": "Johansson", "given": "L", "initials": "L"}, {"family": "Attarha", "given": "S", "initials": "S", "orcid": "0000-0003-4085-9680", "researcher": {"href": "https://publications.scilifelab.se/researcher/0095bacd15234e8488ecc6056ce0883e.json"}}, {"family": "Kolosenko", "given": "I", "initials": "I"}, {"family": "Liu", "given": "J", "initials": "J"}, {"family": "Dagnell", "given": "M", "initials": "M", "orcid": "0000-0002-5925-6794", "researcher": {"href": "https://publications.scilifelab.se/researcher/c36a6602bc714b878fd34f1f32f65672.json"}}, {"family": "Grand\u00e9r", "given": "D", "initials": "D"}, {"family": "Arn\u00e9r", "given": "E S J", "initials": "ESJ", "orcid": "0000-0002-4807-6114", "researcher": {"href": "https://publications.scilifelab.se/researcher/70a545effced47da8a5192a7472ceb8f.json"}}, {"family": "Tamm", "given": "K Pokrovskaja", "initials": "KP", "orcid": "0000-0001-6359-1256", "researcher": {"href": "https://publications.scilifelab.se/researcher/09ec3ee706764024bd748c7a77443845.json"}}, {"family": "Page", "given": "B D G", "initials": "BDG", "orcid": "0000-0002-2101-1329", "researcher": {"href": "https://publications.scilifelab.se/researcher/87dde8251a714d26b3b7cc045b47061f.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "6", "issue": "12", "pages": "eaax7945", "issn-l": "2375-2548"}, "abstract": "Because of its key role in cancer development and progression, STAT3 has become an attractive target for developing new cancer therapeutics. While several STAT3 inhibitors have progressed to advanced stages of development, their underlying biology and mechanisms of action are often more complex than would be expected from specific binding to STAT3. Here, we have identified and optimized a series of compounds that block STAT3-dependent luciferase expression with nanomolar potency. Unexpectedly, our lead compounds did not bind to cellular STAT3 but to another prominent anticancer drug target, TrxR1. We further identified that TrxR1 inhibition induced Prx2 and STAT3 oxidation, which subsequently blocked STAT3-dependent transcription. Moreover, previously identified inhibitors of STAT3 were also found to inhibit TrxR1, and likewise, established TrxR1 inhibitors block STAT3-dependent transcriptional activity. These results provide new insights into the complexities of STAT3 redox regulation while highlighting a novel mechanism to block aberrant STAT3 signaling in cancer cells.", "doi": "10.1126/sciadv.aax7945", "pmid": "32219156", "labels": {"Protein Science Facility (PSF)": "Service", "Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7083616"}, {"db": "pii", "key": "aax7945"}], "notes": [], "created": "2020-09-25T11:19:23.210Z", "modified": "2025-10-17T13:04:28.359Z"}]}