Chemistry:RU-59063

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Short description: Chemical compound
RU-59063
RU-59063.svg
Clinical data
Drug classNonsteroidal androgen; Selective androgen receptor modulator
Identifiers
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC17H18F3N3O2S
Molar mass385.41 g·mol−1
3D model (JSmol)

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 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.[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 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. ↑ 1.0 1.1 1.2 1.3 1.4 "Non-steroidal antiandrogens: synthesis and biological profile of high-affinity ligands for the androgen receptor". J. Steroid Biochem. Mol. Biol. 48 (1): 111–9. January 1994. doi:10.1016/0960-0760(94)90257-7. PMID 8136296. 
  2. ↑ 2.0 2.1 "Selective androgen receptor modulators in drug discovery: medicinal chemistry and therapeutic potential". Curr Top Med Chem 6 (3): 245–70. 2006. doi:10.2174/156802606776173456. PMID 16515480. https://zenodo.org/record/1154960. 
  3. ↑ 3.0 3.1 "Developments in nonsteroidal antiandrogens targeting the androgen receptor". ChemMedChem 5 (10): 1651–61. 2010. doi:10.1002/cmdc.201000259. PMID 20853390. 
  4. ↑ 4.0 4.1 "Recent Developments in Androgen Receptor Antagonists". Archiv der Pharmazie 348 (11): 757–775. 2015. doi:10.1002/ardp.201500187. PMID 26462013. 
  5. ↑ "Development of a second-generation antiandrogen for treatment of advanced prostate cancer". Science 324 (5928): 787–90. 2009. doi:10.1126/science.1168175. PMID 19359544. Bibcode: 2009Sci...324..787T. 
  6. ↑ "Improved therapeutic targeting of the androgen receptor: rational drug design improves survival in castration-resistant prostate cancer". Curr Drug Targets 14 (4): 408–19. 2013. doi:10.2174/1389450111314040003. PMID 23565754. 

External links



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