Δ4-Abiraterone
Δ4-Abiraterone, also known as 17-androsta-4,16-dien-3-one, is a steroidogenesis inhibitor and active metabolite of abiraterone acetate, a drug which is used in the treatment of prostate cancer and is itself a prodrug of abiraterone. D4A is formed from abiraterone by 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase. It is said to be a more potent inhibitor of steroidogenesis than abiraterone, and is partially responsible for the activity of abiraterone acetate.
D4A is specifically an inhibitor of CYP17A1, 3β-HSD, and 5α-reductase. In addition, it has also been found to act as a competitive antagonist of the androgen receptor, with potency reportedly comparable to that of enzalutamide. However, the initial 5α-reduced metabolite of D4A, 3-keto-5α-abiraterone, is an agonist of the AR, and has been found to stimulate prostate cancer progression. The formation of this metabolite can be blocked by the coadministration of dutasteride, a selective and highly potent 5α-reductase inhibitor, and the addition of this medication may improve the effectiveness of abiraterone acetate in the treatment of prostate cancer.