5CJ6

Crystal Structure of a Selective Androgen Receptor Modulator Bound to the Ligand Binding Domain of the Human Androgen Receptor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.07 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.189 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

2-Chloro-4-[[(1R,2R)-2-hydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile: A Transdermal Selective Androgen Receptor Modulator (SARM) for Muscle Atrophy.

Saeed, A.Vaught, G.M.Gavardinas, K.Matthews, D.Green, J.E.Losada, P.G.Bullock, H.A.Calvert, N.A.Patel, N.J.Sweetana, S.A.Krishnan, V.Henck, J.W.Luz, J.G.Wang, Y.Jadhav, P.

(2016) J Med Chem 59: 750-755

  • DOI: https://doi.org/10.1021/acs.jmedchem.5b01168
  • Primary Citation of Related Structures:  
    5CJ6

  • PubMed Abstract: 

    A transdermal SARM has a potential to have therapeutic benefit through anabolic activity in muscle while sparing undesired effects of benign prostate hyperplasia (BPH) and liver-mediated decrease in HDL-C. 2-Chloro-4-[(2-hydroxy-2-methyl-cyclopentyl)amino]-3-methyl-benzonitrile 6 showed the desired muscle and prostate effects in a preclinical ORX rat model. Compound 6 had minimal effect on HDL-C levels in cynomolgus monkeys and showed human cadaver skin permeability, thus making it an effective tool for proof-of-concept studies in a clinical setting.


  • Organizational Affiliation

    Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Androgen receptor283Homo 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
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
small peptide10synthetic constructMutation(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 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
51Y
Query on 51Y

Download Ideal Coordinates CCD File 
C [auth A]2-chloro-4-{[(1R,2R)-2-hydroxy-2-methylcyclopentyl]amino}-3-methylbenzonitrile
C14 H17 Cl N2 O
CXFSVKGROITHRY-TZMCWYRMSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
51Y BindingDB:  5CJ6 Ki: 2 (nM) from 1 assay(s)
EC50: 0.5 (nM) from 1 assay(s)
Binding MOAD:  5CJ6 Ki: 2.03 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.07 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.189 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.803α = 90
b = 65.997β = 90
c = 73.41γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
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: 2016-01-06
    Type: Initial release
  • Version 1.1: 2016-01-20
    Changes: Database references
  • Version 1.2: 2016-02-10
    Changes: Database references
  • Version 1.3: 2024-03-06
    Changes: Data collection, Database references, Derived calculations