Summary
PDB 4KAO deposited: 2013-04-22 modified: 2013-10-09
Title FOCAL ADHESION KINASE CATALYTIC DOMAIN IN COMPLEX WITH 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-(4-pyridin-3- yl-phenyl)-urea
Authors Bomke, J., Dresing, V., Esdar, C., Gradler, U., Greiner, H., Heinrich, T., Holzemann, G., Krier, M., Lehmann, M., Musil, D.
Method X-RAY DIFFRACTION
Structure factors resolution 2.39 rfactor 0.1809 rfree 0.2163
DPI 0.39 theoretical min: 0.27
Related PDB Entries 4K8A 4K9Y 4KAB
Citations

Chemically diverse fragment hits of focal adhesion kinase (FAK) were discovered by surface plasmon resonance (SPR) screening of our in-house fragment library. Site specific binding of the primary hits was confirmed in a competition setup using a high-affinity ATP-site inhibitor of FAK. Protein crystallography revealed the binding mode of 41 out of 48 selected fragment hits within the ATP-site. Structural comparison of the fragment binding modes with a DFG-out inhibitor of FAK initiated first synthetic follow-up optimization leading to improved binding affinity.

Bioorg.Med.Chem.Lett. 2013 Oct; 23(19):5401-5409 doi:10.1016/j.bmcl.2013.07.050

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL2424535
PubMed 23973211 BMCLE8
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
4KAO/1 4KAO 1 monomer 0 1 2 1874
4KAO/2 4KAO 2 monomer 0 1 1 1833