3PDJ | pdb_00003pdj

Crystal Structure of Human 11-beta-Hydroxysteroid Dehydrogenase 1 (11b-HSD1) in Complex with 4,4-Disubstituted Cyclohexylbenzamide Inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 
    0.241 (Depositor), 0.230 (DCC) 
  • R-Value Work: 
    0.211 (Depositor), 0.200 (DCC) 
  • R-Value Observed: 
    0.212 (Depositor) 

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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted NAPClick on this verticalbar to view detailsBest fitted 3PJClick on this verticalbar to view details

This is version 1.1 of the entry. See complete history. 


Literature

Synthesis and Optimization of Novel 4,4-Disubstituted Cyclohexylbenzamide Derivatives as Potent 11beta-HSD1 Inhibitors

Sun, D., Wang, Z., Caille, S., DeGraffenreid, M., Gonzalez-Lopez de Turiso, F., Hungate, R., Jaen, J.C., Jiang, B., Julian, L.D., Kelly, R., McMinn, D.L., Kaizerman, J., Rew, Y., Sudom, A., Tu, H., Ursu, S., Walker, N., Willcockson, M., Yan, X., Ye, Q., Powers, J.P.

(2011) Bioorg Med Chem Lett 21: 405-410

  • DOI: https://doi.org/10.1016/j.bmcl.2010.10.129
  • Primary Citation of Related Structures:  
    3PDJ

  • PubMed Abstract: 

    The synthesis and SAR of a series of 4,4-disubstituted cyclohexylbenzamide inhibitors of 11β-HSD1 are described. Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-human primate ex vivo pharmacodynamic models.

    • Organizational Affiliation: 

    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. daqings@amgen.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Corticosteroid 11-beta-dehydrogenase isozyme 1
A, B
273Homo sapiensMutation(s): 1 
Gene Names: HSD11, HSD11B1, HSD11L
EC: 1.1.1.146 (PDB Primary Data), 1.1.1.201 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P28845 (Homo sapiens)
Explore P28845 
Go to UniProtKB:  P28845
PHAROS:  P28845
GTEx:  ENSG00000117594 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28845
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
3PJ BindingDB:  3PDJ IC50: min: 0.8, max: 37 (nM) from 4 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free:  0.241 (Depositor), 0.230 (DCC) 
  • R-Value Work:  0.211 (Depositor), 0.200 (DCC) 
  • R-Value Observed: 0.212 (Depositor) 
Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 107.044α = 90
b = 107.044β = 90
c = 132.918γ = 120
Software Package:
Software NamePurpose
SCALAdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
MOSFLMdata reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted NAPClick on this verticalbar to view detailsBest fitted 3PJClick on this verticalbar to view details

View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-10-05
    Type: Initial release
  • Version 1.1: 2024-02-21
    Changes: Data collection, Database references, Derived calculations