RU-59063

RU-59063 is a nonsteroidal androgen or selective androgen receptor modulator (SARM) 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 (DHT). The drug is an N-substituted arylthiohydantoin and was derived from the first-generation nonsteroidal antiandrogen (NSAA) 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 (AR) (Ki = 2.2 nM; Ka = 5.4 nM) and 1,000-fold selectivity for the AR over other nuclear steroid hormone receptors, including the PR, ER, GR, and MR. 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 (R-1881). In addition, RU-59063, unlike testosterone and DHT, shows no specific binding to human plasma.