Reshma Rani

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.