3OW6

Crystal Structure of HSP90 with N-Aryl-benzimidazolone I


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.193 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

N-aryl-benzimidazolones as novel small molecule HSP90 inhibitors.

Bruncko, M.Tahir, S.K.Song, X.Chen, J.Ding, H.Huth, J.R.Jin, S.Judge, R.A.Madar, D.J.Park, C.H.Park, C.M.Petros, A.M.Tse, C.Rosenberg, S.H.Elmore, S.W.

(2010) Bioorg Med Chem Lett 20: 7503-7506

  • DOI: https://doi.org/10.1016/j.bmcl.2010.10.010
  • Primary Citation of Related Structures:  
    3OW6, 3OWB, 3OWD

  • PubMed Abstract: 

    We describe the development of a novel series of N-aryl-benzimidazolone HSP90 inhibitors (9) targeting the N-terminal ATP-ase site. SAR development was influenced by structure-based design based around X-ray structures of ligand bound HSP90 complexes. Lead compounds exhibited high binding affinities, ATP-ase inhibition and cellular client protein degradation.


  • Organizational Affiliation

    Cancer Research, Global Pharmaceutical R&D, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. milan.bruncko@abbott.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Heat shock protein HSP 90-alpha207Homo 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
MEX
Query on MEX

Download Ideal Coordinates CCD File 
B [auth A]1-(2,4-dihydroxyphenyl)-1,3-dihydro-2H-benzimidazol-2-one
C13 H10 N2 O3
VCZFDVVMKKLXAN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
MEX BindingDB:  3OW6 IC50: min: 220, max: 8.50e+4 (nM) from 3 assay(s)
PDBBind:  3OW6 IC50: 220 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.193 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.495α = 90
b = 89.482β = 90
c = 88.107γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
ADSCdata collection

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2011-09-21 
  • Deposition Author(s): Park, C.H.

Revision History  (Full details and data files)

  • Version 1.0: 2011-09-21
    Type: Initial release
  • Version 1.1: 2024-02-21
    Changes: Data collection, Database references, Derived calculations