UMB-J17

UMB-J17 is a selective small molecule inhibitor of Poly [ADP-ribose] polymerase 2 (PARP2) that disrupts the interaction between PARP2 and Forkhead box protein A1 (FOXA1). By competing with FOXA1 for binding sites on PARP2, UMB-J17 prevents the recruitment of the androgen receptor (AR) to prostate-specific enhancer regions, thereby inhibiting AR signaling and tumor growth. This mechanism is particularly relevant for castration-resistant prostate cancer (CRPC), including models resistant to enzalutamide, as it suppresses AR signaling without requiring AR-ligand binding. UMB-J17 also demonstrates a synthetic effect when combined with AR pathway inhibitors and enhances the synthetic lethality of PARP inhibition. It was developed through a collaboration involving the University of Massachusetts Boston, Brigham and Women’s Hospital, Harvard Medical School, and Baylor College of Medicine.