azd3514 + abiraterone acetate

AZD3514 + abiraterone acetate is a combination of two orally administered small molecules evaluated for the treatment of castration-resistant prostate cancer (CRPC). **AZD3514** is a first-in-class, orally bioavailable, selective androgen receptor down-regulator (SARD) that inhibits androgen receptor (AR) signaling through two mechanisms: inhibition of ligand-driven nuclear translocation of AR and down-regulation of AR expression. **Abiraterone acetate** is a prodrug of abiraterone and acts as a CYP17 inhibitor, blocking androgen biosynthesis and thereby reducing systemic levels of androgens including dihydrotestosterone (DHT). Combination therapy was tested to evaluate the hypothesis that abiraterone acetate would reduce DHT, thereby enhancing AZD3514’s efficacy in suppressing AR signaling. This combination was tested in small clinical cohorts in men with CRPC, including those who had progressed on abiraterone alone. Clinical development of AZD3514 was discontinued due to insufficient efficacy and unfavorable safety profile, despite some evidence of clinical activity[1][2][3][4][6].