3EKR

Dihydroxylphenyl amides as inhibitors of the Hsp90 molecular chaperone

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.189 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

Dihydroxylphenyl amides as inhibitors of the Hsp90 molecular chaperone.

Kung, P.P., Funk, L., Meng, J., Collins, M., Zhou, J.Z., Johnson, M.C., Ekker, A., Wang, J., Mehta, P., Yin, M.J., Rodgers, C., Davies, J.F., Bayman, E., Smeal, T., Maegley, K.A., Gehring, M.R.

(2008) Bioorg Med Chem Lett 18: 6273-6278

  • DOI: https://doi.org/10.1016/j.bmcl.2008.09.081
  • Primary Citation of Related Structures:  
    3EKO, 3EKR

  • PubMed Abstract: 

    Information from X-ray crystal structures were used to optimize the potency of a HTS hit in a Hsp90 competitive binding assay. A class of novel and potent small molecule Hsp90 inhibitors were thereby identified. Enantio-pure compounds 31 and 33 were potent in PGA-based competitive binding assay and inhibited proliferation of various human cancer cell lines in vitro, with IC(50) values averaging 20 nM.

    • Organizational Affiliation: 

    Pfizer Global Research and Development, La Jolla Laboratories, 10770, Science Center Dr., San Diego, CA 92121, USA. [email protected]


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Heat shock protein HSP 90-alpha
A, B
226Homo sapiensMutation(s): 0 
Gene Names: HSP90AA1, HSP90A, HSPC1, HSPCA
EC: 3.6.4.10
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
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
PY9 PDBBind:  3EKR Ki: 30 (nM) from 1 assay(s)
BindingDB:  3EKR IC50: min: 4000, max: 9300 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.189 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 45.735α = 90
b = 79.511β = 90
c = 118.013γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
CNXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CNXphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-11-25
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description