4BRX

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: 0.239 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.199 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history. 


Literature

Synthesis of Novel Diarylamino-1,3,5-Triazine Derivatives as Fak Inhibitors with Anti-Angiogenic Activity.

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

(2013) Bioorg Med Chem Lett 23: 4552

  • DOI: https://doi.org/10.1016/j.bmcl.2013.06.038
  • Primary Citation of Related Structures:  
    4BRX

  • PubMed Abstract: 

    We report herein the synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK (focal adhesion kinase) inhibitors and the evaluation of their anti-angiogenic activity on HUVEC cells. Generally, the effects of these compounds on endothelial cells could be correlated with their kinase inhibitory activity. The most efficient compounds displayed inhibition of viability against HUVEC cells in the micromolar range, as observed with TAE-226, which was designed by Novartis Pharma AG. X-ray crystallographic analysis of the co-crystal structure for compound 34 revealed that the mode of interaction with the FAK kinase domain is highly similar to that observed in the complex of TAE-226.

    • Organizational Affiliation: 

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


Macromolecules
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(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
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
KGW
Query on KGW
Download Ideal Coordinates CCD File 
B [auth A]2-(4-(2-methoxy-4-morpholinophenylamino)-1,3,5-triazin-2-ylamino)-N-methylbenzamide
C22 H25 N7 O3
MMFUMGAALISETK-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
KGW BindingDB:  4BRX IC50: 320 (nM) from 1 assay(s)
PDBBind:  4BRX IC50: 320 (nM) from 1 assay(s)
Binding MOAD:  4BRX IC50: 320 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.199 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.53α = 90
b = 45.4β = 95.24
c = 66.32γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-07-24
    Type: Initial release
  • Version 1.1: 2013-08-07
    Changes: Database references
  • Version 1.2: 2019-04-03
    Changes: Data collection, Other, Source and taxonomy
  • Version 1.3: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description