Epristeride

Epristeride (INN, USAN, BAN, JAN) (brand names Aipuliete, Chuanliu; former developmental code names ONO-9302, SKF-105,657) is a steroidal 5α-reductase inhibitor that has been marketed in China since 2000 for the treatment of benign prostatic hyperplasia (BPH). It is a selective, transition-state, non-competitive or uncompetitive, irreversible inhibitor of 5α-reductase, and is specific to the type II isoform of the enzyme similarly to finasteride and turosteride. Epristeride was under development for the treatment of BPH, androgenic alopecia (pattern hair loss), and acne vulgaris by SmithKline Beecham (now GlaxoSmithKline) in the 1990s and reached phase III clinical trials in the United States, United Kingdom, and Japan, but ultimately was never marketed in these countries and was developed and introduced for the treatment of BPH by Ono Pharmaceutical in China instead.

Epristeride is unique in its mechanism of action relative to finasteride and dutasteride in that it binds irreversibly to 5α-reductase and results in the formation of an unproductive complex of the 5α-reductase enzyme, the substrate testosterone, and the cofactor NADPH. For this reason, testosterone is caught in a trap, and it was initially speculated that the reciprocal increase in intraprostatic levels of testosterone seen with finasteride and dutasteride should not happen with epristeride. However, subsequent clinical data have not supported this hypothesis. Moreover, in spite of the fact that epristeride is a very potent inhibitor of 5α-reductase type II (0.18–2 nM), it has been found to reduce circulating levels of dihydrotestosterone (DHT) by only 25 to 54% following 8 days of therapy over a dosage range of 0.4 to 160 mg/day. For this reason, relative to other 5α-reductase inhibitors like finasteride and dutasteride, the degree of DHT suppression with epristeride falls short of that desirable for full clinical benefit.