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Non-Steroidal Androgen Receptor Antagonists and Prostate Cancer: a Survey on Chemical Structures Binding this Fast-Mutating Target.
Current Medicinal Chemistry 2018 September 13
The androgen receptor (AR) pathway plays a major role both pathogenesis and progression of prostate cancer. In particular, AR is chiefly involved in the development of castration-resistant prostate cancer (CRPC) as well as in the resistance to the second-generation AR antagonist enzalutamide, and to the selective inhibitor of cytochrome P450 17A1 (CYP17A1) abiraterone. Several small molecules acting as AR antagonists have been designed and developed so far, also as a result of the ability of cells expressing this molecular target to rapidly develop resistance and turn pure receptor antagonists into ineffective or event detrimental molecules. This review covers a survey of most promising classes of non-steroidal androgen receptor antagonists, also providing insights on their mechanism of action and efficacy in treating prostate cancer.
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