3DTW

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.215 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Discovery of amido-benzisoxazoles as potent c-Kit inhibitors.

Kunz, R.K.Rumfelt, S.Chen, N.Zhang, D.Tasker, A.S.Burli, R.Hungate, R.Yu, V.Nguyen, Y.Whittington, D.A.Meagher, K.L.Plant, M.Tudor, Y.Schrag, M.Xu, Y.Ng, G.Y.Hu, E.

(2008) Bioorg Med Chem Lett 18: 5115-5117

  • DOI: https://doi.org/10.1016/j.bmcl.2008.07.111
  • Primary Citation of Related Structures:  
    3DTW

  • PubMed Abstract: 

    Deregulation of the receptor tyrosine kinase c-Kit is associated with an increasing number of human diseases, including certain cancers and mast cell diseases. Interference of c-Kit signaling with multi-kinase inhibitors has been shown clinically to successfully treat gastrointestinal stromal tumors and mastocytosis. Targeted therapy of c-Kit activity may provide therapeutic advantages against off-target effects for non-oncology applications. A new structural class of c-Kit inhibitors is described, including in vitro c-Kit potency, kinase selectivity, and the observed binding mode.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. kunz@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
A96
Query on A96

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
6-chloro-N-pyrimidin-5-yl-3-{[3-(trifluoromethyl)phenyl]amino}-1,2-benzisoxazole-7-carboxamide
C19 H11 Cl F3 N5 O2
FEGRQUWSKADGSP-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
A96 BindingDB:  3DTW IC50: 353 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.215 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.244α = 90
b = 68.355β = 92.16
c = 88.485γ = 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: 2008-09-09
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-08-23
    Changes: Source and taxonomy
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2024-02-21
    Changes: Data collection