Cytochrome P450 17A1 (CYP17A1; also P450c17and P450sccII) is a critically important enzyme in humans
that catalyzes the formation of all endogenous androgens. It is an atypical cytochrome P450 enzyme in that it catalyzes
two distinct types of substrate oxidation. Through its hydroxylase activity, it catalyzes the 17α-hydroxylation of
pregnenolone to 17α-OH pregnenolone. Subsequently, through its C17,20lyase activity, it can further convert 17α-OH
pregnenolone to the androgen dehydroepiandrosterone, which is a precursor to androstenedione, testosterone, and dihydrotestosterone.
The importance of androgens in diseases such as prostate cancer has been appreciated for decades and the
discovery of extra-testicular formation of androgens has helped clarify the pathology of the disease, especially the castrate-
resistant disease. Therefore, specific inhibition of CYP17A1 by therapeutic intervention has been an area of considerable
effort in several research laboratories. This basic research has led to the discovery of several promising drug candidates
followed by the conduct of several clinical trials. Recently, all these efforts have culminated in the first approval by
FDA of an inhibitor of CYP17A1 for the treatment of castrate-resistant prostate cancer. Ongoing clinical trials are now
evaluating the agent in earlier stages of prostate cancer and even rare forms of androgen–dependent breast cancer. Accordingly,
this review focuses on the biochemistry, chemistry, and clinical inhibitors of CYP17A1.