3LZ6

Guinea Pig 11beta hydroxysteroid dehydrogenase with PF-877423


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

The development and SAR of pyrrolidine carboxamide 11beta-HSD1 inhibitors.

Cheng, H.Hoffman, J.Le, P.Nair, S.K.Cripps, S.Matthews, J.Smith, C.Yang, M.Kupchinsky, S.Dress, K.Edwards, M.Cole, B.Walters, E.Loh, C.Ermolieff, J.Fanjul, A.Bhat, G.B.Herrera, J.Pauly, T.Hosea, N.Paderes, G.Rejto, P.

(2010) Bioorg Med Chem Lett 20: 2897-2902

  • DOI: https://doi.org/10.1016/j.bmcl.2010.03.032
  • Primary Citation of Related Structures:  
    3LZ6

  • PubMed Abstract: 

    The design and development of a series of highly selective pyrrolidine carboxamide 11beta-HSD1 inhibitors are described. These compounds including PF-877423 demonstrated potent in vitro activity against both human and mouse 11beta-HSD1 enzymes. In an in vivo assay, PF-877423 inhibited the conversion of cortisone to cortisol. Structure guided optimization effort yielded potent and stable 11beta-HSD1 selective inhibitor 42.


  • Organizational Affiliation

    Pfizer Global Research & Development, La Jolla Labs, 10770 Science Center Drive, San Diego, CA 92121, United States. henry.cheng@pfizer.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, C, D
263Cavia porcellusMutation(s): 0 
Gene Names: HSD11B1
EC: 1.1.1.146
UniProt
Find proteins for Q6QLL4 (Cavia porcellus)
Explore Q6QLL4 
Go to UniProtKB:  Q6QLL4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6QLL4
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 78.398α = 90
b = 83.899β = 90
c = 179.964γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2011-05-04 
  • Deposition Author(s): Pauly, T.A.

Revision History  (Full details and data files)

  • Version 1.0: 2011-05-04
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations, Structure summary