Fig. 7.

Model. AR AF-1 or AR-V7 is maintained in a disordered conformation in molecular condensates in complex with coactivators with a binding region exposed and the C327 and C406 (shown in red dots) buried inside. SARICA binding to the binding region leads to conformation change and dissolution of the condensates. This leads to dissociation of coactivators, exposure of C327 and C406, reorganization of DNA-binding, and change in DNA from euchromatin to heterochromatin. These sequence of events results in inhibition of PCa cell proliferation and tumor growth. SARICA binds to the two cysteines by Michael addition, resulting in inactivation of the region. CoA – coactivator, LLPS – liquid–liquid phase separation.