Subsequent BLI assays validated a direct physical interaction between zeylenol and EGFR, and biological validation demonstrated that zeylenol treatment significantly suppressed GBM cell proliferation and migration while promoting apoptosis, supporting its therapeutic potential as a novel EGFR inhibitor.<h4>Discussion</h4>This study identifies EGFR as a causally relevant therapeutic target in glioma and highlights tremulacin and zeylenol as promising natural EGFR inhibitors, warranting further preclinical development of these compounds as novel glioma therapeutics. This evidence concerns the gene EGFR and glioblastoma.