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