1YIM

Human estrogen receptor alpha ligand-binding domain in complex with compound 4


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.258 
  • R-Value Observed: 0.190 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Estrogen receptor ligands. Part 10: Chromanes: old scaffolds for new SERAMs.

Tan, Q.Blizzard, T.A.Morgan, J.D.Birzin, E.T.Chan, W.Yang, Y.T.Pai, L.Y.Hayes, E.C.DaSilva, C.A.Warrier, S.Yudkovitz, J.Wilkinson, H.A.Sharma, N.Fitzgerald, P.M.Li, S.Colwell, L.Fisher, J.E.Adamski, S.Reszka, A.A.Kimmel, D.DiNinno, F.Rohrer, S.P.Freedman, L.P.Schaeffer, J.M.Hammond, M.L.

(2005) Bioorg Med Chem Lett 15: 1675-1681

  • DOI: https://doi.org/10.1016/j.bmcl.2005.01.046
  • Primary Citation of Related Structures:  
    1YIM, 1YIN

  • PubMed Abstract: 

    The discovery, synthesis, and SAR of chromanes as ER alpha subtype selective ligands are described. X-ray studies revealed that the origin of the ER alpha-selectivity resulted from a C-4 trans methyl substitution to the cis-2,3-diphenyl-chromane platform. Selected compounds from this class demonstrated very potent in vivo antagonism of estradiol in an immature rat uterine weight assay, effectively inhibited ovariectomy-induced bone resorption in a 42 days treatment paradigm, and lowered serum cholesterol levels in ovx'd adult rat models. The best antagonists 8F and 12F also exhibited potent inhibition of MCF-7 cell growth and were shown to be estrogen receptor down-regulators (SERDs).


  • Organizational Affiliation

    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, RY800-B107, Rahway, NJ 07065, USA. qiang_tan@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Estrogen receptor248Homo sapiensMutation(s): 0 
Gene Names: ESR1ESRNR3A1
UniProt & NIH Common Fund Data Resources
Find proteins for P03372 (Homo sapiens)
Explore P03372 
Go to UniProtKB:  P03372
PHAROS:  P03372
GTEx:  ENSG00000091831 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03372
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CM4
Query on CM4

Download Ideal Coordinates CCD File 
B [auth A](2R,3R,4S)-3-(4-HYDROXYPHENYL)-4-METHYL-2-[4-(2-PYRROLIDIN-1-YLETHOXY)PHENYL]CHROMAN-6-OL
C28 H31 N O4
XPVKGTWRXBSJKO-LHXLBICKSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
CM4 BindingDB:  1YIM IC50: 1.5 (nM) from 1 assay(s)
Binding MOAD:  1YIM IC50: 1.5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.258 
  • R-Value Observed: 0.190 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.55α = 90
b = 58.55β = 90
c = 276.6γ = 120
Software Package:
Software NamePurpose
X-GENdata scaling
X-GENdata reduction
SHELXLrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-07-26
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2024-02-14
    Changes: Data collection, Database references, Derived calculations