ONCT-534

ONCT-534 is an orally bioavailable small molecule dual-action androgen receptor inhibitor (DAARI) developed for the treatment of metastatic castration-resistant prostate cancer (mCRPC), particularly in patients who are resistant or refractory to at least one next-generation androgen receptor signaling inhibitor. Its novel mechanism of action involves binding to both the N-terminal domain (NTD) and ligand-binding domain (LBD) of the androgen receptor (AR), leading to inhibition of AR function and degradation of the AR protein. This dual interaction allows ONCT-534 to target tumors expressing AR splice variants and LBD mutations, which are common mechanisms of resistance to current standard-of-care therapies such as enzalutamide, darolutamide, apalutamide, and abiraterone. Preclinical studies have demonstrated activity against unmutated AR as well as multiple forms of altered AR[1][3][5][6][8].