AP-4-139B

AP-4-139B is a small molecule inhibitor of Heat Shock Protein 70 (HSP-70) currently under investigation for the treatment of Coactivator-associated arginine methyltransferase 1 (CARM1)-expressing ovarian cancers. CARM1 is an oncogene frequently amplified in high-grade serous ovarian carcinoma (HGSOC), and HSP-70 serves as a substrate for its enzymatic activity. AP-4-139B was identified through an unbiased evaluation of small-molecule inhibitors for its selective potency against CARM1-expressing epithelial ovarian cancer (EOC) cells. Mechanistically, the drug induces apoptotic cell death in CARM1-high cells by activating apoptotic pathways. Preclinical studies in ovarian cancer cell models and xenograft models have demonstrated that AP-4-139B treatment significantly inhibits tumor growth and induces synthetic lethality in a CARM1-dependent manner.