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PDBsum entry 3ccn
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Contents |
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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X-ray structure of c-met with triazolopyridazine inhibitor.
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Structure:
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Hepatocyte growth factor receptor. Chain: a. Fragment: protein kinase domain,c-met kinase domain. Synonym: hgf receptor, scatter factor receptor, sf receptor, hgf/sf receptor, met proto-oncogene tyrosine kinase, c-met. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: met. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108
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Resolution:
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1.90Å
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R-factor:
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0.238
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R-free:
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0.275
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Authors:
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B.K.Abrecht,J.-C.Harmange,D.Bauer,I.Dussault,A.Long,S.F.Bellon
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Key ref:
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B.K.Albrecht
et al.
(2008).
Discovery and optimization of triazolopyridazines as potent and selective inhibitors of the c-Met kinase.
J Med Chem,
51,
2879-2882.
PubMed id:
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Date:
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26-Feb-08
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Release date:
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29-Apr-08
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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.
275 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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J Med Chem
51:2879-2882
(2008)
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PubMed id:
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Discovery and optimization of triazolopyridazines as potent and selective inhibitors of the c-Met kinase.
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B.K.Albrecht,
J.C.Harmange,
D.Bauer,
L.Berry,
C.Bode,
A.A.Boezio,
A.Chen,
D.Choquette,
I.Dussault,
C.Fridrich,
S.Hirai,
D.Hoffman,
J.F.Larrow,
P.Kaplan-Lefko,
J.Lin,
J.Lohman,
A.M.Long,
J.Moriguchi,
A.O'Connor,
M.H.Potashman,
M.Reese,
K.Rex,
A.Siegmund,
K.Shah,
R.Shimanovich,
S.K.Springer,
Y.Teffera,
Y.Yang,
Y.Zhang,
S.F.Bellon.
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ABSTRACT
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Tumorigenesis is a multistep process in which oncogenes play a key role in tumor
formation, growth, and maintenance. MET was discovered as an oncogene that is
activated by its ligand, hepatocyte growth factor. Deregulated signaling in the
c-Met pathway has been observed in multiple tumor types. Herein we report the
discovery of potent and selective triazolopyridazine small molecules that
inhibit c-Met activity.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.Caballero,
M.Quiliano,
J.H.Alzate-Morales,
M.Zimic,
and
E.Deharo
(2011).
Docking and quantitative structure-activity relationship studies for 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)aniline, 3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline, and 4-(4-amino-2-fluorophenoxy)-2-pyridinylamine derivatives as c-Met kinase inhibitors.
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J Comput Aided Mol Des,
25,
349-369.
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Z.Liang,
D.Zhang,
J.Ai,
L.Chen,
H.Wang,
X.Kong,
M.Zheng,
H.Liu,
C.Luo,
M.Geng,
H.Jiang,
and
K.Chen
(2011).
Identification and synthesis of N'-(2-oxoindolin-3-ylidene)hydrazide derivatives against c-Met kinase.
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Bioorg Med Chem Lett,
21,
3749-3754.
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A.Torkamani,
G.Verkhivker,
and
N.J.Schork
(2009).
Cancer driver mutations in protein kinase genes.
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Cancer Lett,
281,
117-127.
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C.A.Larsen,
W.H.Bisson,
and
R.H.Dashwood
(2009).
Tea catechins inhibit hepatocyte growth factor receptor (MET kinase) activity in human colon cancer cells: kinetic and molecular docking studies.
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J Med Chem,
52,
6543-6545.
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M.L.Peach,
N.Tan,
S.J.Choyke,
A.Giubellino,
G.Athauda,
T.R.Burke,
M.C.Nicklaus,
and
D.P.Bottaro
(2009).
Directed discovery of agents targeting the Met tyrosine kinase domain by virtual screening.
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J Med Chem,
52,
943-951.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
