Nature‐Inspired MYC Inhibitor Disrupts MYC‐Driven Glycolysis and Restricts Ovarian Tumor Growth

Myelocytomatosis oncogene (MYC) inhibitors are not available for clinical applications because the MYC protein is not part of a receptor-ligand pair and lacks a defined binding site for small molecules. GD-07, drug-like small molecule identified throughcheminformatics that selectively binds to the G-quadruplex (G4) in the c-MYC promoter with high binding affinity and selectivity over dsDNA. NMR analysis reveals that GD-07 binds to the upper tetrad of c-MYC G4. It exhibits a favorable pharmacokinetic profile and high cytotoxicity in ovarian cancer (OC) cells (A2780) compared to the standard drug carboplatin. Normal cells show no sensitivity to GD-07, indicating a broad therapeutic window. GD-07 suppresses MYC expression, curbing glucose metabolism, and glycolysis while promoting p53 and proapoptotic markers in OC cells. In patient-derived OC organoids, GD-07 shows greater activity than carboplatin with promising clinical translatability.