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PDBsum entry 4ps3
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Transferase/transferase inhibitor
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PDB id
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4ps3
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References listed in PDB file
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Key reference
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Title
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Structural basis for isoform selectivity in a class of benzothiazole inhibitors of phosphoinositide 3-Kinase γ.
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Authors
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P.N.Collier,
G.Martinez-Botella,
M.Cornebise,
K.M.Cottrell,
J.D.Doran,
J.P.Griffith,
S.Mahajan,
F.Maltais,
C.S.Moody,
E.P.Huck,
T.Wang,
A.M.Aronov.
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Ref.
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J Med Chem, 2015,
58,
517-521.
[DOI no: ]
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PubMed id
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Abstract
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Phosphoinositide 3-kinase γ (PI3Kγ) is an attractive target to potentially
treat a range of disease states. Herein, we describe the evolution of a reported
phenylthiazole pan-PI3K inhibitor into a family of potent and selective
benzothiazole inhibitors. Using X-ray crystallography, we discovered that
compound 22 occupies a previously unreported hydrophobic binding cleft adjacent
to the ATP binding site of PI3Kγ, and achieves its selectivity by exploiting
natural sequence differences among PI3K isoforms in this region.
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