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The overexpression or dysregulation of c\u2010Myc is commonly associated with tumorigenesis in several cancers, including colorectal cancer (CRC). c\u2010Myc forms a heterodimer with its partner MAX to activate the expression of various genes. Here, we synthesized a novel c\u2010Myc\u2010targeting small molecule, 2,2\u2032\u2010((cyclohexylazanedyl)bis(methylene))bis(4\u2010ethylphenol), or ECD, and demonstrate ECD's anticancer activity via interference with the c\u2010Myc\/MAX dimer to promote c\u2010Myc degradation in CRC cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    ,\n                    <jats:italic>in silico<\/jats:italic>\n                    , and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . This study revealed the activity of ECD toward CRC cells as a c\u2010Myc inhibitor. Computer\u2010aided analysis revealed that the effect of ECD was mediated through disturbance of the c\u2010Myc\/MAX complex. Moreover, ECD exhibited cytotoxic activity by inducing DNA damage, leading to apoptotic cell death. This DNA damage\u2010inducing property was also confirmed by whole\u2010proteome profiling of HT29 cells after ECD treatment. In the chick embryo chorioallantoic membrane (CAM) xenograft assay, we demonstrated a remarkable inhibition of the tumorigenic activity upon ECD exposure. In summary, we identified ECD as a novel potent compound targeting the oncoprotein c\u2010Myc that may offer new opportunities for CRC treatment.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70127","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T04:41:51Z","timestamp":1760503311000},"page":"688-708","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A synthetic benzoxazine dimer derivative targets c\u2010Myc to inhibit colorectal cancer progression"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3975-5537","authenticated-orcid":false,"given":"Nicharat","family":"Sriratanasak","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Department of Pharmacology and Physiology Chulalongkorn University  Bangkok Thailand"},{"name":"Faculty of Pharmaceutical Sciences, Center of Excellence in Cancer Cell and 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