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PDBsum entry 4zly
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Transferase/transferase inhibitor
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PDB id
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4zly
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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 a small molecule inhibitor of bruton'S tyrosine kinase.
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Authors
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C.R.Smith,
D.R.Dougan,
M.Komandla,
T.Kanouni,
B.Knight,
J.D.Lawson,
M.Sabat,
E.R.Taylor,
P.Vu,
C.Wyrick.
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Ref.
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J Med Chem, 2015,
58,
5437-5444.
[DOI no: ]
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PubMed id
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Abstract
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The discovery and optimization of a series of 4-aminocinnoline-3-carboxamide
inhibitors of Bruton's tyrosine kinase are reported. A fragment-based screening
approach incorporating X-ray co-crystallography was used to identify a cinnoline
fragment and characterize its binding mode in the ATP binding site of Btk.
Optimization of the fragment hit resulted in the identification of a lead
compound which reduced paw swelling in a dose- and exposure-dependent fashion in
a rat model of collagen-induced arthritis.
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