Targeting androgen receptor for prostate cancer therapy: From small molecules to PROTACs

Prostate cancer (PCa) remains a serious type of cancer for men worldwide. The majority of new PCa cases are associated with androgen receptor (AR) hyperactivity. Various AR-targeting molecules that suppress its activity have been discovered. In this review, we present the already marketed antiandrogens and a selection of structurally and chemically interesting AR-targeting compounds, from a pharmacochemical perspective. Focus has been placed on the applied design approaches, structural evolution and structure-activity relationships of the most prominent compound classes. Passing from the traditional steroidal AR antagonists to the modern AR-targeting proteolysis targeting chimeras (PROTACs), we intend to provide a comprehensive overview on AR-targeting molecules for PCa treatment.