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PDBsum entry 2ihq

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Hormone/growth factor PDB id
2ihq
Jmol
Contents
Protein chain
248 a.a. *
Ligands
LG7
Waters ×76
* Residue conservation analysis
PDB id:
2ihq
Name: Hormone/growth factor
Title: Crystal structure of the rat androgen receptor ligand binding domian complex with an n-aryl- hydroxybicyclohydantoin
Structure: Androgen receptor. Chain: a. Fragment: ligand-binding domain. Synonym: dihydrotestosterone receptor. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: ar. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Monomer (from PQS)
Resolution:
2.00Å     R-factor:   0.209     R-free:   0.269
Authors: J.S.Sack
Key ref: C.Sun et al. (2006). Discovery of potent, orally-active, and muscle-selective androgen receptor modulators based on an N-aryl-hydroxybicyclohydantoin scaffold. J Med Chem, 49, 7596-7599. PubMed id: 17181141 DOI: 10.1021/jm061101w
Date:
27-Sep-06     Release date:   12-Dec-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P15207  (ANDR_RAT) -  Androgen receptor
Seq:
Struc:
 
Seq:
Struc:
902 a.a.
248 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     steroid hormone mediated signaling pathway   2 terms 
  Biochemical function     DNA binding     3 terms  

 

 
DOI no: 10.1021/jm061101w J Med Chem 49:7596-7599 (2006)
PubMed id: 17181141  
 
 
Discovery of potent, orally-active, and muscle-selective androgen receptor modulators based on an N-aryl-hydroxybicyclohydantoin scaffold.
C.Sun, J.A.Robl, T.C.Wang, Y.Huang, J.E.Kuhns, J.A.Lupisella, B.C.Beehler, R.Golla, P.G.Sleph, R.Seethala, A.Fura, S.R.Krystek, Y.An, M.F.Malley, J.S.Sack, M.E.Salvati, G.J.Grover, J.Ostrowski, L.G.Hamann.
 
  ABSTRACT  
 
A novel, N-aryl-bicyclohydantoin selective androgen receptor modulator scaffold was discovered through structure-guided modifications of androgen receptor antagonists. A prototype compound (7R,7aS)-10b from this series is a potent and highly tissue-selective agonist of the androgen receptor. After oral dosing in a rat atrophied levator ani muscle model, (7R,7aS)-10b demonstrated efficacy at restoring levator ani muscle mass to that of intact controls and exhibited >50-fold selectivity for muscle over prostate.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20853390 B.Liu, L.Su, J.Geng, J.Liu, and G.Zhao (2010).
Developments in nonsteroidal antiandrogens targeting the androgen receptor.
  ChemMedChem, 5, 1651-1661.  
20708648 W.Gao (2010).
Androgen receptor as a therapeutic target.
  Adv Drug Deliv Rev, 62, 1277-1284.  
18395206 J.Raber (2008).
AR, apoE, and cognitive function.
  Horm Behav, 53, 706-715.  
18270691 M.Thevis, M.Kohler, A.Thomas, J.Maurer, N.Schlörer, M.Kamber, and W.Schänzer (2008).
Determination of benzimidazole- and bicyclic hydantoin-derived selective androgen receptor antagonists and agonists in human urine using LC-MS/MS.
  Anal Bioanal Chem, 391, 251-261.  
18095383 M.Thevis, M.Kohler, N.Schlörer, M.Kamber, A.Kühn, M.W.Linscheid, and W.Schänzer (2008).
Mass spectrometry of hydantoin-derived selective androgen receptor modulators.
  J Mass Spectrom, 43, 639-650.  
18521833 M.Thevis, and W.Schänzer (2008).
Mass spectrometry of selective androgen receptor modulators.
  J Mass Spectrom, 43, 865-876.  
  19079612 R.Narayanan, M.L.Mohler, C.E.Bohl, D.D.Miller, and J.T.Dalton (2008).
Selective androgen receptor modulators in preclinical and clinical development.
  Nucl Recept Signal, 6, e010.  
18662801 T.Chen (2008).
Nuclear receptor drug discovery.
  Curr Opin Chem Biol, 12, 418-426.  
17992601 G.F.Allan, P.Tannenbaum, T.Sbriscia, O.Linton, M.T.Lai, D.Haynes-Johnson, S.Bhattacharjee, X.Zhang, Z.Sui, and S.G.Lundeen (2007).
A selective androgen receptor modulator with minimal prostate hypertrophic activity enhances lean body mass in male rats and stimulates sexual behavior in female rats.
  Endocrine, 32, 41-51.  
17703938 R.I.Higuchi, A.W.Thompson, J.H.Chen, T.R.Caferro, M.L.Cummings, C.P.Deckhut, M.E.Adams, C.M.Tegley, J.P.Edwards, F.J.López, E.A.Kallel, D.S.Karanewsky, W.T.Schrader, K.B.Marschke, and L.Zhi (2007).
Potent, nonsteroidal selective androgen receptor modulators (SARMs) based on 8H-[1,4]oxazino[2,3-f]quinolin-8-ones.
  Bioorg Med Chem Lett, 17, 5442-5446.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.