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PDBsum entry 7b3v
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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 targeting the folded p-Loop conformation of c-Met.
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Authors
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G.W.Collie,
I.N.Michaelides,
K.Embrey,
C.J.Stubbs,
U.Börjesson,
I.L.Dale,
A.Snijder,
L.Barlind,
K.Song,
P.Khurana,
C.Phillips,
R.I.Storer.
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Ref.
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ACS Med Chem Lett, 2021,
12,
162-167.
[DOI no: ]
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PubMed id
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Abstract
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We report here a fragment screen directed toward the c-MET kinase from which we
discovered a series of inhibitors able to bind to a rare conformation of the
protein in which the P-loop adopts a collapsed, or folded, arrangement.
Preliminary SAR exploration led to an inhibitor (7) with nanomolar
biochemical activity against c-MET and promising cell activity and kinase
selectivity. These findings increase our structural understanding of the folded
P-loop conformation of c-MET and provide a sound structural and chemical basis
for further investigation of this underexplored yet potentially therapeutically
exploitable conformational state.
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