of treatment initiation. The plasma protein binding of enzalutamide is 97 to 98%, while that of N-desmethylenzalutamide (NDME), its major metabolite, is 95%. Enzalutamide is primarily bound to albumin. The medication is metabolized in the liver, mainly by the cytochrome P450 enzymes CYP2C8 and CYP3A4. CYP2C8 is primarily responsible for the formation of NDME. Enzalutamide has a long elimination half-life of 5.8 days on average, with a range of 2.8 to 10.2 days. The elimination half-life of NDME is even longer, at about 7.8 to 8.6 days. Enzalutamide is eliminated 71.0% in urine, 13.6% in bile, and 0.39% in feces. Chemistry Enzalutamide is a synthetic diaryl thiohydantoin derivative and is structurally related to the earlier first-generation NSAAs such as flutamide, nilutamide, and bicalutamide as well as to newer second-generation NSAAs like apalutamide and proxalutamide. History Enzalutamide was discovered by Charles Sawyers, now at the Memorial Sloan–Kettering Cancer Center, and Michael Jung at the University of California, Los Angeles. They and their colleagues synthesized and evaluated nearly 200 thiohydantoin derivatives of RU-59063, an analogue of nilutamide, for AR antagonism in human prostate cancer cells, and identified enzalutamide and RD-162 as lead compounds. These compounds were patented in 2006 and described in 2007. Enzalutamide was developed and marketed by Medivation for the treatment of prostate cancer. It was approved by the U.S. Food and Drug Administration (FDA) for the treatment of mCRPC in the United States in August 2012, and for the treatment of nonmetastatic castration-resistant prostate cancer in July 2018. Enzalutamide was the first new AR antagonist to be approved for the treatment of prostate cancer in over 15 years, following the introduction of the first-generation NSAA bicalutamide in 1995. It was the first second-generation NSAA to be introduced. Research Breast cancer Research suggests that enzalutamide may be effective in the treatment of certain types of breast cancer in women. It has been tested for the treatment of triple-negative, AR-positive breast cancer in a phase II clinical trial. Hirsutism Enzalutamide has been suggested as a potential treatment for hirsutism and hyperandrogenism in women with polycystic ovary syndrome. References External links Astellas Pharma Pfizer brands Benzamides CYP3A4 inducers Fluoroarenes GABAA receptor negative allosteric modulators Hormonal antineoplastic drugs Imidazolidines Lactams Nitriles Nonsteroidal antiandrogens Progonadotropins Prostate cancer Thioureas Trifluoromethyl compounds