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PDBsum entry 5eyc
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Transferase/transferase inhibitor
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PDB id
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5eyc
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References listed in PDB file
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Key reference
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Title
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Discovery of (r)-6-(1-(8-Fluoro-6-(1-Methyl-1h-Pyrazol-4-Yl)-[1,2,4]triazolo[4,3-A]pyridin-3-Yl)ethyl)-3-(2-Methoxyethoxy)-1,6-Naphthyridin-5(6h)-One (amg 337), A potent and selective inhibitor of met with high unbound target coverage and robust in vivo antitumor activity.
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Authors
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A.A.Boezio,
K.W.Copeland,
K.Rex,
B.K albrecht,
D.Bauer,
S.F.Bellon,
C.Boezio,
M.A.Broome,
D.Choquette,
A.Coxon,
I.Dussault,
S.Hirai,
R.Lewis,
M.H.Lin,
J.Lohman,
J.Liu,
E.A.Peterson,
M.Potashman,
R.Shimanovich,
Y.Teffera,
D.A.Whittington,
K.R.Vaida,
J.C.Harmange.
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Ref.
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J Med Chem, 2016,
59,
2328-2342.
[DOI no: ]
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PubMed id
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Abstract
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Deregulation of the receptor tyrosine kinase mesenchymal epithelial transition
factor (MET) has been implicated in several human cancers and is an attractive
target for small molecule drug discovery. Herein, we report the discovery of
compound 23 (AMG 337), which demonstrates nanomolar inhibition of MET kinase
activity, desirable preclinical pharmacokinetics, significant inhibition of MET
phosphorylation in mice, and robust tumor growth inhibition in a MET-dependent
mouse efficacy model.
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