3V49

Structure of ar lbd with activator peptide and sarm inhibitor 1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Observed: 0.185 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Discovery of diarylhydantoins as new selective androgen receptor modulators.

Nique, F.Hebbe, S.Peixoto, C.Annoot, D.Lefrancois, J.-M.Duval, E.Michoux, L.Triballeau, N.Lemoullec, J.M.Mollat, P.Thauvin, M.Prange, T.Minet, D.Clement-Lacroix, P.Robin-Jagerschmidt, C.Fleury, D.Guedin, D.Deprez, P.

(2012) J Med Chem 55: 8225-8235

  • DOI: https://doi.org/10.1021/jm300249m
  • Primary Citation of Related Structures:  
    3V49, 3V4A

  • PubMed Abstract: 

    A novel selective androgen receptor modulator scaffold has been discovered through structural modifications of hydantoin antiandrogens. Several 4-(4-hydroxyphenyl)-N-arylhydantoins displayed partial agonism with nanomolar in vitro potency in transactivation experiments using androgen receptor (AR) transfected cells. In a standard castrated male rat model, several compounds showed good anabolic activity on levator ani muscle, dissociated from the androgenic activity on ventral prostate, after oral dosing at 30 mg/kg. (+)-4-[3,4-Dimethyl-2,5-dioxo-4-(4-hydroxyphenyl)imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile ((+)-11b) displayed anabolic potency with a strong dissociation between levator ani muscle and ventral prostate (A(50) = 0.5 mg/kg vs 70 mg/kg). The binding modes of two compounds, including (+)-11b, within the AR ligand-binding domain have been studied by cocrystallization experiments using a coactivator-like peptide. Both compounds bound to the same site, and the overall structures of the AR were very similar.


  • Organizational Affiliation

    GALAPAGOS, Parc Biocitech, 102 Avenue Gaston Roussel, 93230 Romainville, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Androgen receptor266Homo sapiensMutation(s): 0 
Gene Names: ARDHTRNR3C4
UniProt & NIH Common Fund Data Resources
Find proteins for P10275 (Homo sapiens)
Explore P10275 
Go to UniProtKB:  P10275
PHAROS:  P10275
GTEx:  ENSG00000169083 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP10275
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Androgen receptor, activator peptide11Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P10275 (Homo sapiens)
Explore P10275 
Go to UniProtKB:  P10275
PHAROS:  P10275
GTEx:  ENSG00000169083 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP10275
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PK0
Query on PK0

Download Ideal Coordinates CCD File 
C [auth A]4-[(4R)-4-(4-hydroxyphenyl)-3,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
C19 H14 F3 N3 O3
IHPVXUVRRPAUIQ-GOSISDBHSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
D [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
PK0 PDBBind:  3V49 IC50: 9.6 (nM) from 1 assay(s)
Binding MOAD:  3V49 IC50: 9.6 (nM) from 1 assay(s)
BindingDB:  3V49 IC50: 9.6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Observed: 0.185 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 54.629α = 90
b = 67.331β = 90
c = 69.809γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
SHELXmodel building
SHELXL-97refinement
MOSFLMdata reduction
SCALAdata scaling
SHELXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2012-09-05
    Type: Initial release
  • Version 1.1: 2012-12-19
    Changes: Database references
  • Version 1.2: 2014-10-08
    Changes: Structure summary
  • Version 1.3: 2016-08-31
    Changes: Other
  • Version 1.4: 2018-01-24
    Changes: Structure summary
  • Version 1.5: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description