3CJG

Crystal structure of VEGFR2 in complex with a 3,4,5-trimethoxy aniline containing pyrimidine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor.

Harris, P.A.Boloor, A.Cheung, M.Kumar, R.Crosby, R.M.Davis-Ward, R.G.Epperly, A.H.Hinkle, K.W.Hunter, R.N.Johnson, J.H.Knick, V.B.Laudeman, C.P.Luttrell, D.K.Mook, R.A.Nolte, R.T.Rudolph, S.K.Szewczyk, J.R.Truesdale, A.T.Veal, J.M.Wang, L.Stafford, J.A.

(2008) J Med Chem 51: 4632-4640

  • DOI: https://doi.org/10.1021/jm800566m
  • Primary Citation of Related Structures:  
    3CJF, 3CJG

  • PubMed Abstract: 

    Inhibition of the vascular endothelial growth factor (VEGF) signaling pathway has emerged as one of the most promising new approaches for cancer therapy. We describe herein the key steps starting from an initial screening hit leading to the discovery of pazopanib, N(4)-(2,3-dimethyl-2H-indazol-6-yl)-N(4)-methyl-N(2)-(4-methyl-3-sulfonamidophenyl)-2,4-pyrimidinediamine, a potent pan-VEGF receptor (VEGFR) inhibitor under clinical development for renal-cell cancer and other solid tumors.


  • Organizational Affiliation

    GlaxoSmithKline, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA. philip.a.harris@gsk.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Vascular endothelial growth factor receptor 2309Homo sapiensMutation(s): 0 
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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
KIM
Query on KIM

Download Ideal Coordinates CCD File 
D [auth A]N~4~-methyl-N~4~-(3-methyl-1H-indazol-6-yl)-N~2~-(3,4,5-trimethoxyphenyl)pyrimidine-2,4-diamine
C22 H24 N6 O3
FLXGQDHYCWXTAI-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CSO
Query on CSO
A
L-PEPTIDE LINKINGC3 H7 N O3 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.7α = 90
b = 95.54β = 90
c = 97.01γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MAR345data collection
HKL-2000data reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2008-10-07 
  • Deposition Author(s): Nolte, R.T.

Revision History  (Full details and data files)

  • Version 1.0: 2008-10-07
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Refinement description, Version format compliance
  • Version 1.2: 2017-08-23
    Changes: Source and taxonomy
  • Version 1.3: 2017-10-25
    Changes: Refinement description
  • Version 1.4: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.5: 2023-11-15
    Changes: Data collection