RD-162

RD-162 is a second-generation nonsteroidal antiandrogen (NSAA) which was developed for the treatment of prostate cancer but was never marketed. It acts as a potent and selective silent antagonist of the androgen receptor (AR). The drug is a diarylthiohydantoin derivative. It is closely related to enzalutamide and apalutamide. Both RD-162 and enzalutamide show 5- to 8-fold higher affinity for the AR than the first-generation NSAA bicalutamide, and only 2- to 3-fold lower affinity than dihydrotestosterone (DHT), the major endogenous ligand of the receptor in the prostate gland.

RD-162 and enzalutamide were developed together and were derived from the nonsteroidal androgen RU-59063, which itself was derived from the first-generation NSAA nilutamide. RD-162 and enzalutamide were selected as the lead compounds from a group of over 200 compounds that were synthesized and assayed for antiandrogenic activity. Enzalutamide was ultimately selected from the two for further clinical development and was eventually marketed. RD-162 is also very closely related to apalutamide, with the two compounds differing only by the replacement of a single atom (a carbon atom in one of the phenyl rings of RD-162 swapped with a nitrogen atom in apalutamide). Apalutamide was approved for the treatment of prostate cancer in 2018.