2CCT

HUMAN HSP90 WITH 5-(5-CHLORO-2,4-DIHYDROXY-PHENYL)-4-PIPERAZIN-1-YL- 2H-PYRAZOLE-3-CARBOXYLIC ACID ETHYLAMIDE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.299 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.213 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

4-Amino derivatives of the Hsp90 inhibitor CCT018159.

Barril, X.Beswick, M.C.Collier, A.Drysdale, M.J.Dymock, B.W.Fink, A.Grant, K.Howes, R.Jordan, A.M.Massey, A.Surgenor, A.Wayne, J.Workman, P.Wright, L.

(2006) Bioorg Med Chem Lett 16: 2543-2548

  • DOI: https://doi.org/10.1016/j.bmcl.2006.01.099
  • Primary Citation of Related Structures:  
    2CCS, 2CCT, 2CCU

  • PubMed Abstract: 

    Novel piperazinyl, morpholino and piperidyl derivatives of the pyrazole-based Hsp90 inhibitor CCT018159 are described. Structure-activity relationships have been elucidated by X-ray co-crystal analysis of the new compounds bound to the N-terminal domain of human Hsp90. Key features of the binding mode are essentially identical to the recently reported potent analogue VER-49009. The most potent of the new compounds has a methylsulfonylbenzyl substituent appended to the piperazine nitrogen, possesses an IC50 of less than 600 nM binding against the enzyme and demonstrates low micromolar inhibition of tumour cell proliferation.


  • Organizational Affiliation

    Vernalis Ltd, Granta Park, Cambridge CB1 6GB, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HEAT SHOCK PROTEIN HSP-90 ALPHA236Homo 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
2E1
Query on 2E1

Download Ideal Coordinates CCD File 
B [auth A]5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-PIPERAZIN-1-YL-1H-PYRAZOLE-3-CARBOXAMIDE
C16 H20 Cl N5 O3
SORAKBHHTGVZCS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
2E1 Binding MOAD:  2CCT IC50: 6300 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.299 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.213 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.646α = 90
b = 88.409β = 90
c = 99.574γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
d*TREKdata reduction
d*TREKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2006-02-22
    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: 2017-07-05
    Changes: Data collection
  • Version 1.4: 2018-03-28
    Changes: Database references, Source and taxonomy