RU-59063
RU-59063 is a nonsteroidal androgen or selective androgen receptor modulator which was first described in 1994 and was never marketed. It was originally thought to be a potent antiandrogen, but subsequent research found that it actually possesses dose-dependent androgenic activity, albeit with lower efficacy than dihydrotestosterone. The drug is an N-substituted arylthiohydantoin and was derived from the first-generation nonsteroidal antiandrogen nilutamide. The second-generation NSAAs enzalutamide, RD-162, and apalutamide were derived from RU-59063.
RU-59063 has high affinity for the human androgen receptor and 1,000-fold selectivity for the AR over other nuclear steroid hormone receptors, including the,,, and. It shows 3- and 8-fold higher affinity than testosterone for the rat and human AR, respectively, and up to 100-fold higher affinity for the rat AR than the first-generation NSAAs flutamide, nilutamide, and bicalutamide. It also has slightly higher affinity for the AR than DHT and nearly equal affinity to that of the very-high-affinity AR ligand metribolone. In addition, RU-59063, unlike testosterone and DHT, shows no specific binding to human plasma.
