Definition

An orally bioavailable androgen receptor (AR)-targeted protein degrader, composed of an AR ligand attached to an E3 ligase recognition moiety and utilizing the proteolysis targeting chimera (PROTAC) technology, with potential antineoplastic activity. Upon oral administration, AR degrader ARV-766 targets and binds to the AR ligand binding domain on the AR. E3 ligase is then recruited to the AR by the E3 ligase recognition moiety of ARV-766 and the AR is tagged by ubiquitin. This causes ubiquitination and degradation of AR by the proteasome, and prevents the expression of AR target genes and halts AR-mediated signaling. This inhibits the proliferation of AR-overexpressing tumor cells. In addition, the degradation of the AR releases ARV-766, allowing it to bind to additional AR. AR plays a key role in the proliferation of castration-resistant prostate cancer cells (CRPC). ARV-766 may degrade resistance-driving point mutations of AR, including the L702H mutation associated with treatments including abiraterone.