RU-59063

Last updated
RU-59063
RU-59063.svg
Clinical data
Drug class Nonsteroidal androgen; Selective androgen receptor modulator
Identifiers
  • 4-[3-(4-Hydroxybutyl)-4,4-dimethyl-5-oxo-2-sulfanylideneimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C17H18F3N3O2S
Molar mass 385.41 g·mol−1
3D model (JSmol)
  • N#CC1=CC=C(N2C(N(CCCCO)C(C)(C)C2=O)=S)C=C1C(F)(F)F
  • 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 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 aryl thio hydantoin 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 has a 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 Tooltip progesterone receptor, ER Tooltip estrogen receptor, GR Tooltip glucocorticoid receptor, and MR Tooltip 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

References

  1. 1 2 3 4 5 Teutsch G, Goubet F, Battmann T, Bonfils A, Bouchoux F, Cerede E, Gofflo D, Gaillard-Kelly M, Philibert D (January 1994). "Non-steroidal antiandrogens: synthesis and biological profile of high-affinity ligands for the androgen receptor". J. Steroid Biochem. Mol. Biol. 48 (1): 111–9. doi:10.1016/0960-0760(94)90257-7. PMID   8136296. S2CID   31404295.
  2. 1 2 Cadilla R, Turnbull P (2006). "Selective androgen receptor modulators in drug discovery: medicinal chemistry and therapeutic potential". Curr Top Med Chem. 6 (3): 245–70. doi:10.2174/156802606776173456. PMID   16515480.
  3. 1 2 Liu B, Su L, Geng J, Liu J, Zhao G (2010). "Developments in nonsteroidal antiandrogens targeting the androgen receptor". ChemMedChem. 5 (10): 1651–61. doi:10.1002/cmdc.201000259. PMID   20853390. S2CID   23228778.
  4. 1 2 Ran F, Xing H, Liu Y, Zhang D, Li P, Zhao G (2015). "Recent Developments in Androgen Receptor Antagonists". Archiv der Pharmazie. 348 (11): 757–775. doi:10.1002/ardp.201500187. PMID   26462013. S2CID   11483849.
  5. ↑ Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL (2009). "Development of a second-generation antiandrogen for treatment of advanced prostate cancer". Science. 324 (5928): 787–90. Bibcode:2009Sci...324..787T. doi:10.1126/science.1168175. PMC   2981508 . PMID   19359544.
  6. ↑ Lim AC, Attard G (2013). "Improved therapeutic targeting of the androgen receptor: rational drug design improves survival in castration-resistant prostate cancer". Curr Drug Targets. 14 (4): 408–19. doi:10.2174/1389450111314040003. PMID   23565754.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.