3BM9

Discovery of Benzisoxazoles as Potent Inhibitors of Chaperone Hsp90


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.186 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.165 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Discovery of benzisoxazoles as potent inhibitors of chaperone heat shock protein 90.

Gopalsamy, A.Shi, M.Golas, J.Vogan, E.Jacob, J.Johnson, M.Lee, F.Nilakantan, R.Petersen, R.Svenson, K.Chopra, R.Tam, M.S.Wen, Y.Ellingboe, J.Arndt, K.Boschelli, F.

(2008) J Med Chem 51: 373-375

  • DOI: https://doi.org/10.1021/jm701385c
  • Primary Citation of Related Structures:  
    3BM9, 3BMY

  • PubMed Abstract: 

    Heat shock protein 90 (Hsp90) is a molecular chaperone that is responsible for activating many signaling proteins and is a promising target in tumor biology. We have identified small-molecule benzisoxazole derivatives as Hsp90 inhibitors. Crystallographic studies show that these compounds bind in the ATP binding pocket interacting with the Asp93. Structure based optimization led to the identification of potent analogues, such as 13, with good biochemical profiles.


  • Organizational Affiliation

    Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA. gopalsa@wyeth.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Heat shock protein HSP 90-alpha226Homo sapiensMutation(s): 0 
Gene Names: HSP90AA1HSP90AHSPC1HSPCA
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
BXZ
Query on BXZ

Download Ideal Coordinates CCD File 
B [auth A]4-bromo-6-(6-hydroxy-1,2-benzisoxazol-3-yl)benzene-1,3-diol
C13 H8 Br N O4
LZACPHWPRDKUPK-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
BXZ BindingDB:  3BM9 IC50: 190 (nM) from 1 assay(s)
PDBBind:  3BM9 IC50: 190 (nM) from 1 assay(s)
Binding MOAD:  3BM9 IC50: 190 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.186 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.165 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 66.089α = 90
b = 89.033β = 90
c = 100.172γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
StructureStudiodata collection
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2008-07-08
    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