Small molecule MYC Inhibitor restricts ovarian tumor growth by suppressing c-Myc mediated glycolysis

Ovarian cancer is characterized by aberrant cMYC expression and dysregulated glycolysis. cMYC overexpression is linked to poorer patient survival. Since MYC protein is not part of a receptor-ligand pair and lacks a defined binding site for small molecules, MYC inhibitors are not yet available for clinical applications. Herein, we report the discovery of GD-07 a small molecule identified through high-throughput in silico screening that binds with G-quadruplex (G4) motif in c-Myc promoter. GD-07 effectively stabilizes MYC-G4 through a combination of electrostatic and noncovalent interactions. GD-07 exhibits high cytotoxicity in ovarian cancer cells (A2780) with minimal toxicity in normal cells, providing a wide therapeutic window for targeted cancer therapy. GD-07 suppresses c-Myc expression in ovarian cancer cells, which in turn curtails glucose metabolism and glycolysis. This suppression is accompanied by the promotion of p53 and pro-apoptotic markers, indicating a potential induction of cancer cell apoptosis. Notably, GD-07 exhibit superior efficacy to carboplatin in patient-derived organoids of high-grade serous ovarian cancer (HGSOC), effectively mimicking clinical responses. GD-07 disrupts metabolic pathways and induces apoptosis by modulating key oncogenic and tumor suppressor genes. Our findings highlight GD-07 as a promising therapeutic agent that selectively targets the c-Myc G-quadruplex and disrupts bioenergetics, offering a dual mechanism of action by inhibiting proliferation and promoting apoptosis. GD-07 represents a novel approach with high translational potential for treating resistant and metastatic ovarian cancer, laying the foundation for future development of next-generation cancer therapeutics.