4NY9

Crystal Structure Of the Human PXR-LBD In Complex With N-{(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl}-3-hydroxy-3-methylbutanamide

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.298 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.232 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history. 


Literature

Discovery of the CCR1 antagonist, BMS-817399, for the treatment of rheumatoid arthritis.

Santella, J.B., Gardner, D.S., Duncia, J.V., Wu, H., Dhar, M., Cavallaro, C., Tebben, A.J., Carter, P.H., Barrish, J.C., Yarde, M., Briceno, S.W., Cvijic, M.E., Grafstrom, R.R., Liu, R., Patel, S.R., Watson, A.J., Yang, G., Rose, A.V., Vickery, R.D., Caceres-Cortes, J., Caporuscio, C., Camac, D.M., Khan, J.A., An, Y., Foster, W.R., Davies, P., Hynes, J.

(2014) J Med Chem 57: 7550-7564

  • DOI: https://doi.org/10.1021/jm5003167
  • Primary Citation of Related Structures:  
    4NY9

  • PubMed Abstract: 

    High-affinity, functionally potent, urea-based antagonists of CCR1 have been discovered. Modulation of PXR transactivation has revealed the selective and orally bioavailable CCR1 antagonist BMS-817399 (29), which entered clinical trials for the treatment of rheumatoid arthritis.

    • Organizational Affiliation: 

    Bristol Myers Squibb Company , P.O. Box 4000, Princeton, New Jersey 08543-4000, United States.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Nuclear receptor subfamily 1 group I member 2290Homo sapiensMutation(s): 0 
Gene Names: NR1I2, PXR
UniProt & NIH Common Fund Data Resources
Find proteins for O75469 (Homo sapiens)
Explore O75469 
Go to UniProtKB:  O75469
PHAROS:  O75469
GTEx:  ENSG00000144852 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO75469
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
2Q4
Query on 2Q4
Download Ideal Coordinates CCD File 
B [auth A]N-{(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl}-3-hydroxy-3-methylbutanamide
C23 H35 Cl N2 O4
PTNKPLPRPJERNR-XXBNENTESA-N
GOL
Query on GOL
Download Ideal Coordinates CCD File 
C [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
2Q4 BindingDB:  4NY9 EC50: min: 1800, max: 2300 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.298 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.232 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.76α = 90
b = 91.76β = 90
c = 85.651γ = 90
Software Package:
Software NamePurpose
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-08-27
    Type: Initial release
  • Version 1.1: 2014-12-10
    Changes: Database references
  • Version 1.2: 2017-11-22
    Changes: Refinement description
  • Version 1.3: 2024-02-28
    Changes: Data collection, Database references, Derived calculations