3CP9

Crystal structure of the VEGFR2 kinase domain in complex with a pyridone inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.211 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Discovery of Aryl Aminoquinazoline Pyridones as Potent, Selective, and Orally Efficacious Inhibitors of Receptor Tyrosine Kinase c-Kit.

Hu, E.Tasker, A.White, R.D.Kunz, R.K.Human, J.Chen, N.Burli, R.Hungate, R.Novak, P.Itano, A.Zhang, X.Yu, V.Nguyen, Y.Tudor, Y.Plant, M.Flynn, S.Xu, Y.Meagher, K.L.Whittington, D.A.Ng, G.Y.

(2008) J Med Chem 51: 3065-3068

  • DOI: https://doi.org/10.1021/jm800188g
  • Primary Citation of Related Structures:  
    3CP9, 3CPB, 3CPC

  • PubMed Abstract: 

    Inhibition of c-Kit has the potential to treat mast cell associated fibrotic diseases. We report the discovery of several aminoquinazoline pyridones that are potent inhibitors of c-Kit with greater than 200-fold selectivity against KDR, p38, Lck, and Src. In vivo efficacy of pyridone 16 by dose-dependent inhibition of histamine release was demonstrated in a rodent pharmacodynamic model of mast cell activation.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Amgen Inc, Thousand Oaks, CA 91320-1799, USA. ehu@amgen.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Vascular endothelial growth factor receptor 2
A, B
314Homo sapiensMutation(s): 3 
Gene Names: KDRFLK1
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P35968 (Homo sapiens)
Explore P35968 
Go to UniProtKB:  P35968
PHAROS:  P35968
GTEx:  ENSG00000128052 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35968
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
C19
Query on C19

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
3-(2-aminoquinazolin-6-yl)-1-(3,3-dimethylindolin-6-yl)-4-methylpyridin-2(1H)-one
C24 H23 N5 O
LHLGUOHREUTYTO-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A, B
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Binding Affinity Annotations 
IDSourceBinding Affinity
C19 PDBBind:  3CP9 IC50: 48 (nM) from 1 assay(s)
BindingDB:  3CP9 IC50: 48 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.211 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.57α = 90
b = 67.17β = 93.076
c = 89.102γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
DENZOdata reduction
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-06-17
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-07-26
    Changes: Source and taxonomy
  • Version 1.3: 2018-06-13
    Changes: Data collection, Database references, Source and taxonomy
  • Version 1.4: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.5: 2024-02-21
    Changes: Data collection