4C7T

Focal Adhesion Kinase catalytic domain in complex with a diarylamino- 1,3,5-triazine inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.220 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Inhibition of Both Focal Adhesion Kinase and Fibroblast Growth Factor Receptor 2 Pathways Induces Anti-Tumor and Anti-Angiogenic Activities.

Dao, P.Jarray, R.Smith, N.Lepelletier, Y.Le Coq, J.Lietha, D.Hadj-Slimane, R.Herbeuval, J.P.Garbay, C.Raynaud, F.Chen, H.

(2014) Cancer Lett 348: 88

  • DOI: https://doi.org/10.1016/j.canlet.2014.03.007
  • Primary Citation of Related Structures:  
    4C7T

  • PubMed Abstract: 

    FAK and FGFR2 signaling pathways play important roles in cancer development, progression and tumor angiogenesis. PHM16 is a novel ATP competitive inhibitor of FAK and FGFR2. To evaluate the therapeutic efficacy of this agent, we examined its anti-angiogenic effect in HUVEC and its anti-tumor effect in different cancer cell lines. We showed PHM16 inhibited endothelial cell viability, adherence and tube formation along with the added ability to induce endothelial cell apoptosis. This compound significantly delayed tumor cell growth. Together, these data showed that inhibition of both FAK and FGFR2 signaling pathways can enhance anti-tumor and anti-angiogenic activities.


  • Organizational Affiliation

    CNRS, UMR8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CBNIT, Université Paris Descartes, PRES Sorbonne Paris Cité, UFR Biomédicale, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
FOCAL ADHESION KINASE 1276Gallus gallusMutation(s): 0 
EC: 2.7.10.2
UniProt
Find proteins for Q00944 (Gallus gallus)
Explore Q00944 
Go to UniProtKB:  Q00944
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ00944
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5RI
Query on 5RI

Download Ideal Coordinates CCD File 
B [auth A]N-methyl-2-[[4-[(3,4,5-trimethoxyphenyl)amino]-1,3,5-triazin-2-yl]amino]benzamide
C20 H22 N6 O4
UQGQBHYGCQYHMP-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
5RI Binding MOAD:  4C7T IC50: 400 (nM) from 1 assay(s)
BindingDB:  4C7T IC50: 400 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.220 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.37α = 90
b = 45.28β = 95.11
c = 66.66γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-04-02
    Type: Initial release
  • Version 1.1: 2014-04-09
    Changes: Database references
  • Version 1.2: 2014-05-28
    Changes: Database references
  • Version 1.3: 2019-04-03
    Changes: Data collection, Other, Source and taxonomy
  • Version 1.4: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description