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PDBsum entry 4wun
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Transferase/transferase inhibitor
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PDB id
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4wun
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References listed in PDB file
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Key reference
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Title
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The 1.65 å resolution structure of the complex of azd4547 with the kinase domain of fgfr1 displays exquisite molecular recognition.
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Authors
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Y.Yosaatmadja,
A.V.Patterson,
J.B.Smaill,
C.J.Squire.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2015,
71,
525-533.
[DOI no: ]
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PubMed id
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Abstract
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The fibroblast growth factor receptor (FGFR) family are expressed widely in
normal tissues and play a role in tissue repair, inflammation, angiogenesis and
development. However, aberrant signalling through this family can lead to
cellular proliferation, evasion of apoptosis and induction of angiogenesis,
which is implicated in the development of many cancers and also in drug
resistance. The high frequency of FGFR amplification or mutation in multiple
cancer types is such that this family has been targeted for the discovery of
novel, selective drug compounds, with one of the most recently discovered being
AZD4547, a subnanomolar (IC50) FGFR1 inhibitor developed by AstraZeneca and
currently in clinical trials. The 1.65 Å resolution crystal structure of
AZD4547 bound to the kinase domain of FGFR1 has been determined and reveals
extensive drug-protein interactions, an integral network of water molecules and
the tight closure of the FGFR1 P-loop to form a long, narrow crevice in which
the AZD4547 molecule binds.
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