{"entity": "publication", "iuid": "23a842334d594221bedbe0cf5ff9cd28", "timestamp": "2026-08-23T09:25:30.394Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/23a842334d594221bedbe0cf5ff9cd28.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/23a842334d594221bedbe0cf5ff9cd28"}}, "title": "Discovery of a 6-Aminobenzo[b]thiophene 1,1-Dioxide Derivative (K2071) with a Signal Transducer and Activator of Transcription 3 Inhibitory, Antimitotic, and Senotherapeutic Activities.", "authors": [{"family": "Oleksak", "given": "Patrik", "initials": "P", "orcid": "0000-0002-6850-7671", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/346b2e1937fd4ff0a4a0fa895ae635aa.json"}}, {"family": "Rysanek", "given": "David", "initials": "D", "orcid": "0000-0002-5131-0055", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8dc6659a04f9480799fcad9c1825aff2.json"}}, {"family": "Vancurova", "given": "Marketa", "initials": "M"}, {"family": "Vasicova", "given": "Pavla", "initials": "P"}, {"family": "Urbancokova", "given": "Alexandra", "initials": "A"}, {"family": "Novak", "given": "Josef", "initials": "J"}, {"family": "Maurencova", "given": "Dominika", "initials": "D"}, {"family": "Kashmel", "given": "Pavel", "initials": "P"}, {"family": "Houserova", "given": "Jana", "initials": "J"}, {"family": "Mikyskova", "given": "Romana", "initials": "R"}, {"family": "Novotny", "given": "Ondrej", "initials": "O"}, {"family": "Reinis", "given": "Milan", "initials": "M", "orcid": "0000-0001-7083-2898", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/37bb3c1ba48b45ce9dc905739c01d76a.json"}}, {"family": "Juda", "given": "Pavel", "initials": "P", "orcid": "0000-0002-6421-3852", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9b178b9b5af14b7eb8efa85195b11c94.json"}}, {"family": "Hons", "given": "Miroslav", "initials": "M"}, {"family": "Kroupova", "given": "Jirina", "initials": "J", "orcid": "0000-0002-7946-6975", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b214bd2e8ebb4227a10dfc292184a1ce.json"}}, {"family": "Sedlak", "given": "David", "initials": "D", "orcid": "0000-0003-0074-335X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f82128dbfc234876af9d3435a024b8b2.json"}}, {"family": "Sulimenko", "given": "Tetyana", "initials": "T"}, {"family": "Draber", "given": "Pavel", "initials": "P"}, {"family": "Chlubnova", "given": "Marketa", "initials": "M"}, {"family": "Nepovimova", "given": "Eugenie", "initials": "E"}, {"family": "Kuca", "given": "Kamil", "initials": "K", "orcid": "0000-0001-9664-1109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ae2c926b546c44cc87de82bc159801c4.json"}}, {"family": "Lisa", "given": "Miroslav", "initials": "M", "orcid": "0000-0001-9227-5375", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/384738aa92884e36b3e9703588a75b4c.json"}}, {"family": "Andrys", "given": "Rudolf", "initials": "R"}, {"family": "Kobrlova", "given": "Tereza", "initials": "T"}, {"family": "Soukup", "given": "Ondrej", "initials": "O", "orcid": "0000-0001-6376-8701", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fce4207229ad45349ae434af79d277f4.json"}}, {"family": "Janousek", "given": "Jiri", "initials": "J"}, {"family": "Prchal", "given": "Lukas", "initials": "L"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}, {"family": "Musilek", "given": "Kamil", "initials": "K"}, {"family": "Hodny", "given": "Zdenek", "initials": "Z"}], "type": "journal article", "published": "2024-09-13", "journal": {"title": "ACS pharmacology & translational science", "issn": "2575-9108", "volume": "7", "issue": "9", "pages": "2755-2783", "issn-l": "2575-9108"}, "abstract": "6-Nitrobenzo[b]thiophene 1,1-dioxide (Stattic) is a potent signal transducer and activator of the transcription 3 (STAT3) inhibitor developed originally for anticancer therapy. However, Stattic harbors several STAT3 inhibition-independent biological effects. To improve the properties of Stattic, we prepared a series of analogues derived from 6-aminobenzo[b]thiophene 1,1-dioxide, a compound directly obtained from the reduction of Stattic, that includes a methoxybenzylamino derivative (K2071) with optimized physicochemical characteristics, including the ability to cross the blood-brain barrier. Besides inhibiting the interleukin-6-stimulated activity of STAT3 mediated by tyrosine 705 phosphorylation, K2071 also showed cytotoxicity against a set of human glioblastoma-derived cell lines. In contrast to the core compound, a part of K2071 cytotoxicity reflected a STAT3 inhibition-independent block of mitotic progression in the prophase, affecting mitotic spindle formation, indicating that K2071 also acts as a mitotic poison. Compared to Stattic, K2071 was significantly less thiol-reactive. In addition, K2071 affected cell migration, suppressed cell proliferation in tumor spheroids, exerted cytotoxicity for glioblastoma temozolomide-induced senescent cells, and inhibited the secretion of the proinflammatory cytokine monocyte chemoattractant protein 1 (MCP-1) in senescent cells. Importantly, K2071 was well tolerated in mice, lacking manifestations of acute toxicity. The structure-activity relationship analysis of the K2071 molecule revealed the necessity of the para-substituted methoxyphenyl motif for antimitotic but not overall cytotoxic activity of its derivatives. Altogether, these results indicate that compound K2071 is a novel Stattic-derived STAT3 inhibitor and a mitotic poison with anticancer and senotherapeutic properties that is effective on glioblastoma cells and may be further developed as an agent for glioblastoma therapy.", "doi": "10.1021/acsptsci.4c00190", "pmid": "39296273", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11406704"}], "notes": [], "created": "2026-08-20T08:12:58.594Z", "modified": "2026-08-20T08:13:22.129Z"}