Bromodomain and extra-terminal proteins (BETs) are potential targets for the therapeutic treatment of prostate cancer (PC).Herein,we report the design,the synthesis,and a structure-activity relationship study of 6-(3,5-dimethylisoxazol-4-yl)benzo[cd]indol-2(1H)-one derivative as novel selective BET inhibitors.One representative compound,19 (Y06014),bound to BRD4(1) in the low micromolar range and demonstrated high selectivity for BRD4(1) over other non-BET bromodomain-containing proteins.This molecule also potently inhibited cell growth,colony formation,and mRNA expression of AR-regulated genes in PC cell lines.Y06014 also shows stronger activity than the second-generation antiandrogen enzalutamide.Y06014 may serve as a new small molecule probe for further validation of BET as a molecular target for PC drug development.