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The nuclear export receptor chromosome region maintenance 1 (CRM1) has recently emerged as a promising therapeutic target, as its inhibition can simultaneously disrupt multiple key oncogenic drivers. Herein, whether chromenone derivatives, known for detecting thiol\u2010containing molecules, can function as CRM1 inhibitors is explored. Several chromenone\u2010based derivatives are synthesized and it is demonstrated that they inhibit CRM1\u2010driven nuclear export in a structure\u2010 and dose\u2010dependent manner. A preliminary structure\u2013activity relationship is established, providing a rationale for selective CRM1 binding based on molecular docking studies. Additionally, it is showed that the active chromenone derivatives effectively inhibit the nuclear export of endogenous nuclear export signal\u2010containing substrates in GBM cells. Several of these compounds exhibit selective cytotoxicity against GBM cell lines, highlighting their potential as targeted therapies for GBM.<\/jats:p>","DOI":"10.1002\/cbic.202500195","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T09:14:47Z","timestamp":1745399687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chromenone Derivatives as CRM1 Inhibitors for Targeting Glioblastoma"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3440-8373","authenticated-orcid":false,"given":"Salvatore","family":"Princiotto","sequence":"first","affiliation":[{"name":"DeFENS Department of Food, Environmental and Nutritional Sciences Universit\u00e0 degli Studi di Milano  Via Festa del Perdono 720122 Milan Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9576-1766","authenticated-orcid":false,"given":"Luc\u00eda","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Sols\u2010Morreale Biomedical Research Institute (IIBM) Spanish National Research Council (CSIC) Universidad Aut\u00f3noma de Madrid (UAM)  Calle Arturo Duperier 428029 Madrid Spain"}]},{"given":"Luc\u00eda","family":"Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Sols\u2010Morreale Biomedical Research Institute (IIBM) Spanish National Research Council (CSIC) Universidad Aut\u00f3noma de Madrid (UAM)  Calle Arturo Duperier 428029 Madrid Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3246-5964","authenticated-orcid":false,"given":"Jo\u00e3o G. 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