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PDBsum entry 2oo8
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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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Synthesis, structural analysis, and sar studies of triazine derivatives as potent, selective tie-2 inhibitors
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Structure:
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Angiopoietin-1 receptor. Chain: x. Fragment: kinase domain. Synonym: tyrosine-protein kinase receptor tie-2, htie2, tyrosine- protein kinase receptor tek, p140 tek, tunica interna endothelial cell kinase, cd202b antigen. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: tek, tie2. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.20Å
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R-factor:
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0.235
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R-free:
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0.279
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Authors:
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S.F.Bellon,J.Kim
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Key ref:
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B.L.Hodous
et al.
(2007).
Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors.
Bioorg Med Chem Lett,
17,
2886-2889.
PubMed id:
DOI:
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Date:
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25-Jan-07
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Release date:
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20-Mar-07
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PROCHECK
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Headers
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References
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Q02763
(TIE2_HUMAN) -
Angiopoietin-1 receptor from Homo sapiens
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Seq:
Struc:
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1124 a.a.
259 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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DOI no:
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Bioorg Med Chem Lett
17:2886-2889
(2007)
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PubMed id:
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Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors.
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B.L.Hodous,
S.D.Geuns-Meyer,
P.E.Hughes,
B.K.Albrecht,
S.Bellon,
S.Caenepeel,
V.J.Cee,
S.C.Chaffee,
M.Emery,
J.Fretland,
P.Gallant,
Y.Gu,
R.E.Johnson,
J.L.Kim,
A.M.Long,
M.Morrison,
P.R.Olivieri,
V.F.Patel,
A.Polverino,
P.Rose,
L.Wang,
H.Zhao.
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ABSTRACT
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A novel class of selective Tie-2 inhibitors was derived from a multi-kinase
inhibitor 1. By reversing the amide connectivity and incorporating aminotriazine
or aminopyridine hinge-binding moieties, excellent Tie-2 potency and KDR
selectivity could be achieved with 3-substituted terminal aryl rings. X-ray
co-crystal structure analysis aided inhibitor design. This series was evaluated
on the basis of potency, selectivity, and rat pharmacokinetic parameters.
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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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F.Nussenbaum,
and
I.M.Herman
(2010).
Tumor angiogenesis: insights and innovations.
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J Oncol,
2010,
132641.
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I.Kufareva,
and
R.Abagyan
(2008).
Type-II kinase inhibitor docking, screening, and profiling using modified structures of active kinase states.
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J Med Chem,
51,
7921-7932.
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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
