Biochanin A inhibits the activity of androgen receptor mutants to suppress the development of prostate cancer.

Androgens and the androgen receptor (AR) play a central role in the development and progression of prostate cancer. While biochanin A (BCA) has been reported to suppress androgen synthesis and overcome resistance to abiraterone and enzalutamide, its direct effects on AR, particularly mutant AR, remain unclear. In this study, we systematically investigated the binding affinity and functional impact of BCA on a panel of clinically relevant AR mutations to identify patient subgroups that may benefit from BCA treatment. Our results demonstrated that BCA exhibits high-binding affinity toward the ART877A and ARW741C mutants. Our findings reveal a previously unrecognized mechanism by which BCA directly targets specific AR mutants, in addition to inhibiting androgen biosynthesis. This study provides mechanistic insights into the mutation-selective activity of BCA and supports its potential clinical application in molecularly stratified prostate cancer.