5G3J

Discovery of New Selective Glucocorticoid Receptor Agonist Leads


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.198 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of New Selective Glucocorticoid Receptor Agonist Leads.

Berger, M.Rehwinkel, H.Schmees, N.Schacke, H.Edman, K.Wissler, L.Reichel, A.Jaroch, S.

(2017) Bioorg Med Chem Lett 27: 437

  • DOI: https://doi.org/10.1016/j.bmcl.2016.12.047
  • Primary Citation of Related Structures:  
    5G3J

  • PubMed Abstract: 

    We report on the discovery of two new lead series for the development of glucocorticoid receptor agonists. Firstly, the discovery of tetrahydronaphthalenes led to metabolically stable and dissociated compounds. Their binding mode to the glucocorticoid receptor could be elucidated through an X-ray structure. Closer inspection into the reaction path and analyses of side products revealed a new amino alcohol series also addressing the glucocorticoid receptor and demonstrating strong anti-inflammatory activity in vitro.


  • Organizational Affiliation

    Medicinal Chemistry Berlin, Candidate Generation & External Innovation, Drug Discovery, Bayer Pharma AG, D-13353 Berlin, Germany. Electronic address: [email protected].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GLUCOCORTICOID RECEPTOR280Homo sapiensMutation(s): 4 
UniProt & NIH Common Fund Data Resources
Find proteins for P04150 (Homo sapiens)
Explore P04150 
Go to UniProtKB:  P04150
PHAROS:  P04150
GTEx:  ENSG00000113580 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04150
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
NUCLEAR RECEPTOR COACTIVATOR 214Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q15596 (Homo sapiens)
Explore Q15596 
Go to UniProtKB:  Q15596
PHAROS:  Q15596
GTEx:  ENSG00000140396 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15596
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CPS
Query on CPS

Download Ideal Coordinates CCD File 
C [auth A]3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE
C32 H58 N2 O7 S
UMCMPZBLKLEWAF-BCTGSCMUSA-N
E7T
Query on E7T

Download Ideal Coordinates CCD File 
E [auth A]5-[[(1S,2R,4R)-4-ethyl-6,7-bis(fluoranyl)-2,5-bis(oxidanyl)-2-(trifluoromethyl)-3,4-dihydro-1H-naphthalen-1-yl]amino]-1H-quinolin-2-one
C22 H19 F5 N2 O3
VZPLUSXTJULLCS-SYQZRHMFSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
D [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
E7T BindingDB:  5G3J IC50: min: 1.2, max: 63 (nM) from 4 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.198 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 84.263α = 90
b = 84.263β = 90
c = 106.678γ = 120
Software Package:
Software NamePurpose
BUSTERrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-02-15
    Type: Initial release
  • Version 1.1: 2017-08-23
    Changes: Data collection
  • Version 1.2: 2019-04-03
    Changes: Data collection, Source and taxonomy
  • Version 1.3: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description