2BYI

3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as Inhibitors of the Hsp90 Molecular Chaperone


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.197 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

3-(5-Chloro-2,4-Dihydroxyphenyl)-Pyrazole-4-Carboxamides as Inhibitors of the Hsp90 Molecular Chaperone.

Brough, P.A.Barril, X.Beswick, M.Dymock, B.W.Drysdale, M.J.Wright, L.Grant, K.Massey, A.Surgenor, A.Workman, P.

(2005) Bioorg Med Chem Lett 15: 5197

  • DOI: https://doi.org/10.1016/j.bmcl.2005.08.091
  • Primary Citation of Related Structures:  
    2BYH, 2BYI

  • PubMed Abstract: 

    Information from X-ray crystal structures of Hsp90 inhibitors bound to the human Hsp90 molecular chaperone was used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as novel inhibitors of Hsp90. Accessing an extra interaction with the protein via Phe138 gave a significant increase in binding potency compared to similar analogues that do not make this interaction.


  • Organizational Affiliation

    Vernalis Ltd, Granta Park, Great Abington, Cambridge CB1 6GB, UK. p.brough@vernalis.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HEAT SHOCK PROTEIN HSP90-ALPHA235Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P07900 (Homo sapiens)
Explore P07900 
Go to UniProtKB:  P07900
PHAROS:  P07900
GTEx:  ENSG00000080824 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07900
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
2DD
Query on 2DD

Download Ideal Coordinates CCD File 
B [auth A]3-(5-CHLORO-2,4-DIHYDROXY-PHENYL)-1H-PYRAZOLE-4-CARBOXYLIC ACID 4-SULFAMOYL-BENZYLAMIDE
C17 H15 Cl N4 O5 S
OOHYJGNSESWEFT-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
2DD Binding MOAD:  2BYI IC50: 461 (nM) from 1 assay(s)
PDBBind:  2BYI IC50: 461 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.197 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.296α = 90
b = 44.049β = 115.28
c = 54.176γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
d*TREKdata reduction
d*TREKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-10-12
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description