The Preclinical Characterization Of The N-Terminal Domain Androgen Receptor Inhibitor, Epi-7386, For The Treatment Of Prostate Cancer

Background: Androgen receptor (AR) signaling remains an important driver even in late stage prostate cancer. While current anti-androgen therapies targeting the ligand binding domain (LBD) are effective, resistance to these therapies ultimately develops and new methods of inhibiting the AR pathway are needed. ESSA’s compounds selectively target the N-terminal domain (NTD), a region of the AR which is essential for AR transactivation. EPI-7386 is a potent and metabolically stable AR NTD inhibitor which has been selected for clinical evaluation based on its biological effects, pharmaceutical characteristics, preclinical efficacy, and toxicology profile as described below.