1YWN

Vegfr2 in complex with a novel 4-amino-furo[2,3-d]pyrimidine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.71 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.206 

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Ligand Structure Quality Assessment 


This is version 1.6 of the entry. See complete history


Literature

Novel 4-amino-furo[2,3-d]pyrimidines as Tie-2 and VEGFR2 dual inhibitors

Miyazaki, Y.Matsunaga, S.Tang, J.Maeda, Y.Nakano, M.Philippe, R.J.Shibahara, M.Liu, W.Sato, H.Wang, L.Nolte, R.T.

(2005) Bioorg Med Chem Lett 15: 2203-2207

  • DOI: https://doi.org/10.1016/j.bmcl.2005.03.034
  • Primary Citation of Related Structures:  
    1YWN

  • PubMed Abstract: 

    A novel class of furo[2,3-d]pyrimidines has been discovered as potent dual inhibitors of Tie-2 and VEGFR2 receptor tyrosine kinases (TK) and a diarylurea moiety at 5-position shows remarkably enhanced activity against both enzymes. One of the most active compounds, 4-amino-3-(4-((2-fluoro-5-(trifluoromethyl)phenyl)amino-carbonylamino)phenyl)-2-(4-methoxyphenyl)furo[2,3-d]pyrimidine (7k) is <3 nM on both TK receptors and the activity is rationalized based on the X-ray crystal structure.


  • Organizational Affiliation

    GlaxoSmithKline K.K., Tsukuba Research Laboratories, 43, Wadai, Tsukuba 300-4247, Ibaraki, Japan. yasushi.miyazaki@gsk.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Vascular endothelial growth factor receptor 2316Homo sapiensMutation(s): 3 
Gene Names: KDRFLK1
EC: 2.7.1.112
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
LIF
Query on LIF

Download Ideal Coordinates CCD File 
B [auth A]N-{4-[4-AMINO-6-(4-METHOXYPHENYL)FURO[2,3-D]PYRIMIDIN-5-YL]PHENYL}-N'-[2-FLUORO-5-(TRIFLUOROMETHYL)PHENYL]UREA
C27 H19 F4 N5 O3
FGZIONRFHVNRJB-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Binding Affinity Annotations 
IDSourceBinding Affinity
LIF BindingDB:  1YWN IC50: min: 3, max: 15.49 (nM) from 3 assay(s)
Binding MOAD:  1YWN IC50: 3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.71 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.206 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.953α = 90
b = 95.595β = 90
c = 95.803γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MAR345data collection
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-08-23
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.5: 2023-08-23
    Changes: Data collection, Refinement description
  • Version 1.6: 2023-11-15
    Changes: Data collection