Sriratanasak N.Nutho B.Wattanathana W.Phaonakrop N.Panasawatwong B.Erlenbach-Wuensch K.Roytrakul S.Schneider-Stock R.Chanvorachote P.Mahidol University2025-10-272025-10-272025-01-01Molecular Oncology (2025)15747891https://repository.li.mahidol.ac.th/handle/123456789/112762The c-Myc protein is a well-known oncoprotein that plays a crucial role in regulating cell growth, proliferation, and differentiation. The overexpression or dysregulation of c-Myc is commonly associated with tumorigenesis in several cancers, including colorectal cancer (CRC). c-Myc forms a heterodimer with its partner MAX to activate the expression of various genes. Here, we synthesized a novel c-Myc-targeting small molecule, 2,2′-((cyclohexylazanedyl)bis(methylene))bis(4-ethylphenol), or ECD, and demonstrate ECD's anticancer activity via interference with the c-Myc/MAX dimer to promote c-Myc degradation in CRC cells in vitro, in silico, and in vivo. This study revealed the activity of ECD toward CRC cells as a c-Myc inhibitor. Computer-aided analysis revealed that the effect of ECD was mediated through disturbance of the c-Myc/MAX complex. Moreover, ECD exhibited cytotoxic activity by inducing DNA damage, leading to apoptotic cell death. This DNA damage-inducing property was also confirmed by whole-proteome 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-Myc that may offer new opportunities for CRC treatment.Biochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1002/1878-0261.701272-s2.0-1050192303711878026141088563