2C6E

Aurora A kinase activated mutant (T287D) in complex with a 5- aminopyrimidinyl quinazoline inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.200 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Sar and Inhibitor Complex Structure Determination of a Novel Class of Potent and Specific Aurora Kinase Inhibitors.

Heron, N.M.Anderson, M.Blowers, D.P.Breed, J.Eden, J.M.Green, S.Hill, G.B.Johnson, T.Jung, F.H.Mcmiken, H.H.J.Mortlock, A.A.Pannifer, A.D.Pauptit, R.A.Pink, J.Roberts, N.J.Rowsell, S.

(2006) Bioorg Med Chem Lett 16: 1320

  • DOI: https://doi.org/10.1016/j.bmcl.2005.11.053
  • Primary Citation of Related Structures:  
    2C6D, 2C6E

  • PubMed Abstract: 

    A novel series of 5-aminopyrimidinyl quinazolines has been developed from anilino-quinazoline 1, which was identified in a high throughput screen for Aurora A. Introduction of the pyrimidine ring and optimisation of the substituents both on this ring and at the C7 position of the quinazoline led to the discovery of compounds that are highly specific Aurora kinase inhibitors. Co-crystallisation of one of these inhibitors with a fragment of Aurora A shows the importance of the benzamido group in achieving selectivity.


  • Organizational Affiliation

    AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG,UK. Nicola.Heron@astrazeneca.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SERINE/THREONINE-PROTEIN KINASE 6
A, B
283Homo sapiensMutation(s): 0 
EC: 2.7.1.37
UniProt & NIH Common Fund Data Resources
Find proteins for O14965 (Homo sapiens)
Explore O14965 
Go to UniProtKB:  O14965
PHAROS:  O14965
GTEx:  ENSG00000087586 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO14965
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HPM
Query on HPM

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
N-{5-[(7-{[(2S)-2-HYDROXY-3-PIPERIDIN-1-YLPROPYL]OXY}-6-METHOXYQUINAZOLIN-4-YL)AMINO]PYRIMIDIN-2-YL}BENZAMIDE
C28 H31 N7 O4
WHHFZOIADLFZRX-NRFANRHFSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
HPM PDBBind:  2C6E IC50: 0.8 (nM) from 1 assay(s)
BindingDB:  2C6E IC50: 0.8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.200 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.603α = 90
b = 88.421β = 90.01
c = 67.832γ = 90
Software Package:
Software NamePurpose
CNXrefinement
MOSFLMdata reduction
CCP4data scaling
EPMRphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-01-11
    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: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description