RU-59063

RU-59063 is a nonsteroidal androgen or selective androgen receptor modulator (SARM) which was first described in 1994 and was never marketed.^[1] 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).^[1][2] The drug is an N-substituted arylthiohydantoin and was derived from the first-generation nonsteroidal antiandrogen (NSAA) nilutamide.^[1][3] The second-generation NSAAs enzalutamide, RD-162, and apalutamide were derived from RU-59063.^[4][5]

RU-59063

Clinical data
Drug class	Nonsteroidal androgen; Selective androgen receptor modulator
Identifiers
IUPAC name 4-[3-(4-Hydroxybutyl)-4,4-dimethyl-5-oxo-2-sulfanylideneimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
CAS Number	155180-53-3
PubChem CID	197655
ChemSpider	171095
UNII	3LRS7FXN3G
ChEMBL	ChEMBL331820
Chemical and physical data
Formula	C17H18F3N3O2S
Molar mass	385.41 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1(C(=O)N(C(=S)N1CCCCO)C2=CC(=C(C=C2)C#N)C(F)(F)F)C
InChI InChI=1S/C17H18F3N3O2S/c1-16(2)14(25)23(15(26)22(16)7-3-4-8-24)12-6-5-11(10-21)13(9-12)17(18,19)20/h5-6,9,24H,3-4,7-8H2,1-2H3 Key:FIDNKDVRTLFETI-UHFFFAOYSA-N

RU-59063 has a high affinity for the human androgen receptor (AR) (K_i = 2.2 nM; K_a = 5.4 nM) and 1,000-fold selectivity for the AR over other nuclear steroid hormone receptors, including the PRTooltip progesterone receptor, ERTooltip estrogen receptor, GRTooltip glucocorticoid receptor, and MRTooltip mineralocorticoid receptor.^[3][2] 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.^[1] It also has a slightly higher affinity for the AR than DHT and nearly equal affinity to that of the very-high-affinity AR ligand metribolone (R-1881).^[4][6] In addition, RU-59063, unlike testosterone and DHT, shows no specific binding to human plasma.^[1]

See also

• Cyanonilutamide
• RU-58642
• RU-58841