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PDBsum entry 4kab
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Transferase/transferase inhibitor
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PDB id
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4kab
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References listed in PDB file
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Key reference
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Title
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Fragment-Based discovery of focal adhesion kinase inhibitors.
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Authors
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U.Grädler,
J.Bomke,
D.Musil,
V.Dresing,
M.Lehmann,
G.Hölzemann,
H.Greiner,
C.Esdar,
M.Krier,
T.Heinrich.
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Ref.
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Bioorg Med Chem Lett, 2013,
23,
5401-5409.
[DOI no: ]
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PubMed id
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Abstract
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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.
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