17α-Hydroxylase/17,20-Lyase (P45017α) Inhibitors in the Treatment of Prostate Cancer: A Review

Prostate cancer is an age-related disease and a major cause of death in Western countries. A large proportion of prostate cancers have been found to be dependent on androgens for growth and various therapeutic approaches have aimed at either decreasing androgen levels or blocking their action. One method of decreasing androgen levels is through inhibition of enzymes involved in the bio-synthetic pathway, for example, the P450 enzyme complex 17 alpha-hydroxylase/C17,20-lyase (P450(17 alpha)), which catalyses the conversion of pregnenolone and progesterone into the androgen precursors dehydroepiandrosterone and androstenedione respectively. A number of researchers have targeted this enzyme and have produced potent steroidal and non-steroidal inhibitors. This review looks at the various inhibitors that have been developed, focussing mainly on more recent inhibitors reported over the last ten years. Some mention is also given to structural requirements suggested to be important for potent activity.