Chemical Degradation of Androgen Receptor (AR) Using Bicalutamide Analog-Thalidomide PROTACs

A series of PROTACs (PROteolysis-TArgeting Chimeras) consisting of bicalutamide analogs and thalidomides were designed, synthesized, and biologically evaluated as novel androgen receptor (AR) degraders. In particular, we found that PROTAC compound 13b could successfully demonstrate a targeted degradation of AR in AR-positive cancer cells and might be a useful chemical probe for the investigation of AR-dependent cancer cells, as well as a potential therapeutic candidate for prostate cancers.

Automated summary

A series of PROTACs consisting of bicalutamide analogs and thalidomides were designed, synthesized, and evaluated for their ability to degrade androgen receptor in cancer cells. Among them, compound 13b showed targeted degradation of AR in AR-positive cancer cells, suggesting its potential as a chemical probe for AR-dependent cancer cells and a therapeutic candidate for prostate cancers.