2I0G

Benzopyrans are Selective Estrogen Receptor beta Agonists (SERBAs) with Novel Activity in Models of Benign Prostatic Hyperplasia


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.235 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Benzopyrans are selective estrogen receptor Beta agonists with novel activity in models of benign prostatic hyperplasia.

Norman, B.H.Dodge, J.A.Richardson, T.I.Borromeo, P.S.Lugar, C.W.Jones, S.A.Chen, K.Wang, Y.Durst, G.L.Barr, R.J.Montrose-Rafizadeh, C.Osborne, H.E.Amos, R.M.Guo, S.Boodhoo, A.Krishnan, V.

(2006) J Med Chem 49: 6155-6157

  • DOI: https://doi.org/10.1021/jm060491j
  • Primary Citation of Related Structures:  
    2I0G, 2I0J

  • PubMed Abstract: 

    Benzopyran selective estrogen receptor beta agonist-1 (SERBA-1) shows potent, selective binding and agonist function in estrogen receptor beta (ERbeta) in vitro assays. X-ray crystal structures of SERBA-1 in ERalpha and beta help explain observed beta-selectivity of this ligand. SERBA-1 in vivo demonstrates involution of the ventral prostate in CD-1 mice (ERbeta effect), while having no effect on gonadal hormone levels (ERalpha effect) at 10x the efficacious dose, consistent with in vitro properties of this molecule.


  • Organizational Affiliation

    Discovery Chemistry Research, Bone and Inflammation Research, Lead Optimization Biology, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. norman@lilly.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Estrogen receptor beta
A, B
257Homo sapiensMutation(s): 0 
Gene Names: ESR2ESTRBNR3A2
UniProt & NIH Common Fund Data Resources
Find proteins for Q92731 (Homo sapiens)
Explore Q92731 
Go to UniProtKB:  Q92731
PHAROS:  Q92731
GTEx:  ENSG00000140009 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ92731
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
I0G
Query on I0G

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-1,2,3,3A,4,9B-HEXAHYDROCYCLOPENTA[C]CHROMEN-8-OL
C18 H18 O3
XIESSJVMWNJCGZ-VKJFTORMSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
I0G BindingDB:  2I0G Ki: min: 0.17, max: 0.47 (nM) from 3 assay(s)
EC50: 0.66 (nM) from 1 assay(s)
Binding MOAD:  2I0G Ki: 0.19 (nM) from 1 assay(s)
PDBBind:  2I0G Ki: 0.19 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.235 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.196α = 90
b = 63.196β = 90
c = 249.255γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
HKL-2000data reduction
AMoREphasing
CNXrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2006-10-24 
  • Deposition Author(s): Wang, Y.

Revision History  (Full details and data files)

  • Version 1.0: 2006-10-24
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-18
    Changes: Refinement description
  • Version 1.4: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description