RD 162 was optimized from a screen for non-steroidal antiandrogens that retain activity in the setting of increased androgen receptor expression. RD 162 binds to the androgen receptor with greater relative affinity than the clinically used antiandrogen bicalutamide, reduce the efficiency of its nuclear translocation and impair both DNA binding to androgen response elements and recruitment of coactivators. RD 162 is orally available and induce tumor regression in mouse models of castration-resistant human prostate cancer.