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.
Structure factors resolution 2.39 rfactor 0.1809 rfree 0.2163
DPI 0.39 theoretical min: 0.27
Related PDB Entries 4K8A 4K9Y 4KAB

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