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PDBsum entry 4brx
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PDB id:
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Transferase
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Title:
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Focal adhesion kinase catalytic domain in complex with a diarylamino- 1,3,5-triazine inhibitor
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Structure:
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Focal adhesion kinase 1. Chain: a. Fragment: kinase domain, residues 411-686. Synonym: fadk 1, focal adhesion kinase-related nonkinase, frnk, p41/p43frnk, protein-tyrosine kinase 2, p125fak, pp125fak. Engineered: yes
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Source:
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Gallus gallus. Chicken. Organism_taxid: 9031. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high five.
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Resolution:
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2.05Å
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R-factor:
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0.199
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R-free:
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0.239
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Authors:
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J.Le Coq,D.Lietha
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Key ref:
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P.Dao
et al.
(2013).
Synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity.
Bioorg Med Chem Lett,
23,
4552-4556.
PubMed id:
DOI:
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Date:
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05-Jun-13
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Release date:
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24-Jul-13
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PROCHECK
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Headers
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References
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Q00944
(FAK1_CHICK) -
Focal adhesion kinase 1 from Gallus gallus
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Seq:
Struc:
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1053 a.a.
260 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.7.10.2
- non-specific protein-tyrosine kinase.
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Reaction:
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
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L-tyrosyl-[protein]
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+
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ATP
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=
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O-phospho-L-tyrosyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Bioorg Med Chem Lett
23:4552-4556
(2013)
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PubMed id:
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Synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity.
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P.Dao,
R.Jarray,
J.Le Coq,
D.Lietha,
A.Loukaci,
Y.Lepelletier,
R.Hadj-Slimane,
C.Garbay,
F.Raynaud,
H.Chen.
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ABSTRACT
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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.
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Links
