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PDBsum entry 4gg5
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Transferase/transferase inhibitor
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PDB id
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4gg5
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PDB id:
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| Name: |
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Transferase/transferase inhibitor
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Title:
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Crystal structure of cmet in complex with novel inhibitor
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Structure:
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Hepatocyte growth factor receptor. Chain: a. Synonym: hgf receptor, hgf/sf receptor, proto-oncogenE C-met, scatter factor receptor, sf receptor, tyrosine-protein kinase met. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: c-met, met. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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2.42Å
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R-factor:
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0.216
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R-free:
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0.268
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Authors:
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Q.F.Liu,T.T.Chen,Y.C.Xu
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Key ref:
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K.Wu
et al.
(2012).
Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: synthesis and SAR study as tyrosine kinase c-Met inhibitors.
Bioorg Med Chem Lett,
22,
6368-6372.
PubMed id:
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Date:
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05-Aug-12
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Release date:
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03-Oct-12
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PROCHECK
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Headers
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References
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P08581
(MET_HUMAN) -
Hepatocyte growth factor receptor from Homo sapiens
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Seq:
Struc:
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1390 a.a.
274 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.7.10.1
- receptor protein-tyrosine kinase.
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Reaction:
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
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L-tyrosyl-[protein]
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+
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ATP
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=
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O-phospho-L-tyrosyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Bioorg Med Chem Lett
22:6368-6372
(2012)
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PubMed id:
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Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: synthesis and SAR study as tyrosine kinase c-Met inhibitors.
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K.Wu,
J.Ai,
Q.Liu,
T.Chen,
A.Zhao,
X.Peng,
Y.Wang,
Y.Ji,
Q.Yao,
Y.Xu,
M.Geng,
A.Zhang.
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ABSTRACT
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Two series of new analogues were designed by replacing the quinoline scaffold of
our earlier lead 2 (zgwatinib) with quinoxaline and pyrido[2,3-d]pyrimidine
frameworks. Moderate c-Met inhibitory activity was observed in the quinoxaline
series. Among the pyrido[2,3-d]pyrimidine series, compounds 13a-c possessing an
O-linkage were inactive, whilst the N-linked analogues 15a-c retained c-Met
inhibitory potency. Highest activity was observed in the 3-nitrobenzyl analog
15b that showed an IC(50) value of 6.5nM. Further structural modifications based
on this compound were undergoing.
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