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PDBsum entry 1nde

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Transcription PDB id
1nde
Jmol
Contents
Protein chain
231 a.a. *
Ligands
MON
Waters ×43
* Residue conservation analysis
PDB id:
1nde
Name: Transcription
Title: Estrogen receptor beta with selective triazine modulator
Structure: Estrogen receptor beta. Chain: a. Fragment: residues 256-501. Synonym: er-beta. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: estrb. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
3.00Å     R-factor:   0.240     R-free:   0.273
Authors: B.R.Henke,T.G.Consler,N.Go,R.L.Hale,D.R.Hohman,S.A.Jones,A.T L.B.Moore,J.T.Moore,L.A.Orband-Miller,R.G.Robinett,J.Sheari P.K.Spearing,E.L.Stewart,P.S.Turnbull,S.L.Weaver,S.P.Willia G.B.Wisely,M.H.Lambert
Key ref: B.R.Henke et al. (2002). A new series of estrogen receptor modulators that display selectivity for estrogen receptor beta. J Med Chem, 45, 5492-5505. PubMed id: 12459017 DOI: 10.1021/jm020291h
Date:
09-Dec-02     Release date:   18-Dec-02    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q92731  (ESR2_HUMAN) -  Estrogen receptor beta
Seq:
Struc:
 
Seq:
Struc:
530 a.a.
231 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     4 terms  

 

 
DOI no: 10.1021/jm020291h J Med Chem 45:5492-5505 (2002)
PubMed id: 12459017  
 
 
A new series of estrogen receptor modulators that display selectivity for estrogen receptor beta.
B.R.Henke, T.G.Consler, N.Go, R.L.Hale, D.R.Hohman, S.A.Jones, A.T.Lu, L.B.Moore, J.T.Moore, L.A.Orband-Miller, R.G.Robinett, J.Shearin, P.K.Spearing, E.L.Stewart, P.S.Turnbull, S.L.Weaver, S.P.Williams, G.B.Wisely, M.H.Lambert.
 
  ABSTRACT  
 
A series of 1,3,5-triazine-based estrogen receptor (ER) modulators that are modestly selective for the ERbeta subtype are reported. Compound 1, which displayed modest potency and selectivity for ERbeta vs ERalpha, was identified via high-throughput screening utilizing an ERbeta SPA-based binding assay. Subsequent analogue preparation resulted in the identification of compounds such as 21 and 43 that display 25- to 30-fold selectivity for ERbeta with potencies in the 10-30 nM range. These compounds profile as full antagonists at ERbeta and weak partial agonists at ERalpha in a cell-based reporter gene assay. In addition, the X-ray crystal structure of compound 15 complexed with the ligand binding domain of ERbeta has been solved and was utilized in the design of more conformationally restrained analogues such as 31 in an attempt to increase selectivity for the ERbeta subtype.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19967775 F.Minutolo, M.Macchia, B.S.Katzenellenbogen, and J.A.Katzenellenbogen (2011).
Estrogen receptor β ligands: Recent advances and biomedical applications.
  Med Res Rev, 31, 364-442.  
20958921 H.Ojha, P.Gahlot, A.K.Tiwari, M.Pathak, and R.Kakkar (2011).
Quantitative structure activity relationship study of 2,4,6-trisubstituted-s-triazine derivatives as antimalarial inhibitors of Plasmodium falciparum dihydrofolate reductase.
  Chem Biol Drug Des, 77, 57-62.  
20148675 P.Huang, V.Chandra, and F.Rastinejad (2010).
Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics.
  Annu Rev Physiol, 72, 247-272.  
18027887 E.Bourguet, I.Correia, B.Dorgeret, G.Chassaing, S.Sicsic, and S.Ongeri (2008).
Synthesis and conformational studies of pseudopeptides containing an unsymmetrical triazine scaffold.
  J Pept Sci, 14, 596-609.  
18317942 M.Spreafico, E.Boriani, E.Benfenati, and M.Novic (2007).
Structural features of diverse ligands influencing binding affinities to estrogen alpha and estrogen beta receptors. Part II. Molecular descriptors calculated from conformation of the ligands in the complex resulting from previous docking study.
  Mol Divers, 11, 171-181.  
16402138 A.Vessières, S.Top, W.Beck, E.Hillard, and G.Jaouen (2006).
Metal complex SERMs (selective oestrogen receptor modulators). The influence of different metal units on breast cancer cell antiproliferative effects.
  Dalton Trans, (), 529-541.  
16892386 J.T.Moore, J.L.Collins, and K.H.Pearce (2006).
The nuclear receptor superfamily and drug discovery.
  ChemMedChem, 1, 504-523.  
16914190 P.Ascenzi, A.Bocedi, and M.Marino (2006).
Structure-function relationship of estrogen receptor alpha and beta: impact on human health.
  Mol Aspects Med, 27, 299-402.  
16648639 R.W.Hsieh, S.S.Rajan, S.K.Sharma, Y.Guo, E.R.DeSombre, M.Mrksich, and G.L.Greene (2006).
Identification of ligands with bicyclic scaffolds provides insights into mechanisms of estrogen receptor subtype selectivity.
  J Biol Chem, 281, 17909-17919.
PDB codes: 1zky 2b1v 2fai
15715931 B.Wu, J.Gao, and M.W.Wang (2005).
Development of a complex scintillation proximity assay for high-throughput screening of PPARgamma modulators.
  Acta Pharmacol Sin, 26, 339-344.  
15709961 K.W.Nettles, and G.L.Greene (2005).
Ligand control of coregulator recruitment to nuclear receptors.
  Annu Rev Physiol, 67, 309-333.  
15254553 A.T.Deyrup, M.Tretiakova, A.Khramtsov, and A.G.Montag (2004).
Estrogen receptor beta expression in vascular neoplasia: an analysis of 53 benign and malignant cases.
  Mod Pathol, 17, 1372-1377.  
14696075 M.Cecchini, P.Kolb, N.Majeux, and A.Caflisch (2004).
Automated docking of highly flexible ligands by genetic algorithms: a critical assessment.
  J Comput Chem, 25, 412-422.  
15090225 N.T.Peekhaus, M.Ferrer, T.Chang, O.Kornienko, J.E.Schneeweis, T.S.Smith, I.Hoffman, L.J.Mitnaul, J.Chin, P.A.Fischer, T.A.Blizzard, E.T.Birzin, W.Chan, J.Inglese, B.Strulovici, S.P.Rohrer, and J.M.Schaeffer (2003).
A beta-lactamase-dependent Gal4-estrogen receptor beta transactivation assay for the ultra-high throughput screening of estrogen receptor beta agonists in a 3456-well format.
  Assay Drug Dev Technol, 1, 789-800.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.