Non-steroidal CYP17A1 Inhibitors: Discovery and Assessment

CYP17A1 is an enzyme that plays a major role in steroidogenesisand is critically involved in the biosynthesis of steroid hormones.Therefore, it remains an attractive target in several serious hormone-dependentcancer diseases, such as prostate cancer and breast cancer. The medicinalchemistry community has been committed to the discovery and developmentof CYP17A1 inhibitors for many years, particularly for the treatmentof castration-resistant prostate cancer. The current Perspective reflectsupon the discovery and evaluation of non-steroidal CYP17A1 inhibitorsfrom a medicinal chemistry angle. Emphasis is placed on the structuralaspects of the target, key learnings from the presented chemotypes,and design guidelines for future inhibitors.

Automated summary

CYP17A1 is a key enzyme in steroidogenesis and is associated with hormone-dependent cancers. The discovery and development of CYP17A1 inhibitors has been a focus in medicinal chemistry, particularly for treating castration-resistant prostate cancer. This Perspective discusses non-steroidal CYP17A1 inhibitors, emphasizing the target's structure, key findings from different compounds, and design principles for future inhibitors.