4BQG

structure of HSP90 with an inhibitor bound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Discovery of Nms-E973 as Novel, Selective and Potent Inhibitor of Heat Shock Protein 90 (Hsp90).

Brasca, M.G.Mantegani, S.Amboldi, N.Bindi, S.Caronni, D.Casale, E.Ceccarelli, W.Colombo, N.De Ponti, A.Donati, D.Ermoli, A.Fachin, G.Felder, E.R.Ferguson, R.D.Fiorelli, C.Guanci, M.Isacchi, A.Pesenti, E.Polucci, P.Riceputi, L.Sola, F.Visco, C.Zuccotto, F.Fogliatto, G.

(2013) Bioorg Med Chem 21: 7047

  • DOI: https://doi.org/10.1016/j.bmc.2013.09.018
  • Primary Citation of Related Structures:  
    4BQG, 4BQJ

  • PubMed Abstract: 

    Novel small molecule inhibitors of heat shock protein 90 (Hsp90) were discovered with the help of a fragment based drug discovery approach (FBDD) and subsequent optimization with a combination of structure guided design, parallel synthesis and application of medicinal chemistry principles. These efforts led to the identification of compound 18 (NMS-E973), which displayed significant efficacy in a human ovarian A2780 xenograft tumor model, with a mechanism of action confirmed in vivo by typical modulation of known Hsp90 client proteins, and with a favorable pharmacokinetic and safety profile.


  • Organizational Affiliation

    Nerviano Medical Sciences S.r.l., Oncology, Viale Pasteur 10, 20014 Nerviano, MI, Italy. Electronic address: gabriella.brasca@nervianoms.com.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HSP90AA1 PROTEIN230Homo 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
50Q
Query on 50Q

Download Ideal Coordinates CCD File 
B [auth A]5-(3,4-dichloro-phenoxy)-benzene-1,3-diol
C12 H8 Cl2 O3
MACRIRNSUBEWEK-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
50Q PDBBind:  4BQG Kd: 600 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.807α = 90
b = 90.346β = 90
c = 98.471γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2013-10-23
    Type: Initial release
  • Version 1.1: 2013-10-30
    Changes: Database references
  • Version 1.2: 2017-06-28
    Changes: Data collection