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 struc-turally 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.

Automated summary

This review presents an overview of marketed antiandrogens and various interesting AR-targeting compounds from a pharmacochemical perspective. The design approaches, structural evolution, and structure-activity relationships of prominent compound classes are emphasized. The transition from traditional steroidal AR antagonists to modern AR-targeting PROTACs is discussed, providing a comprehensive overview of AR-targeting molecules for PCa treatment.