4KAO

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

Summary for 4KAO

• Entry DOI: 10.2210/pdb4kao/pdb
• Related: 4GU6 4GU9 4K8A 4K9Y 4KAB
• Descriptor: Focal adhesion kinase 1, 1-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-3-[4-(pyridin-3-yl)phenyl]urea, SULFATE ION, ... (4 entities in total)
• Functional Keywords: tyrosine protein kinase, transferase, atp binding, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cell junction, focal adhesion: Q05397
• Total number of polymer chains: 2
• Total formula weight: 65555.56

Authors

Musil, D.,Graedler, U.,Heinrich, T.,Lehmann, M.,Dresing, V. (deposition date: 2013-04-22, release date: 2013-09-11, Last modification date: 2024-11-27)

Primary citation

Gradler, U.,Bomke, J.,Musil, D.,Dresing, V.,Lehmann, M.,Holzemann, G.,Greiner, H.,Esdar, C.,Krier, M.,Heinrich, T.
Fragment-based discovery of focal adhesion kinase inhibitors.
Bioorg.Med.Chem.Lett., 23:5401-5409, 2013

PubMed Abstract: 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.

PubMed: 23973211
DOI: 10.1016/j.bmcl.2013.07.050

Experimental method

X-RAY DIFFRACTION (2.39 Å)