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PDBsum entry 3ekn
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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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Insulin receptor kinase complexed with an inhibitor
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Structure:
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Insulin receptor. Chain: a. Fragment: kinase domain. Synonym: ir, insulin receptor subunit alpha, insulin receptor subunit beta. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: insr. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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2.20Å
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R-factor:
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0.214
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R-free:
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0.274
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Authors:
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S.Chamberlain,C.Atkins,F.Deanda,M.Dumble,R.Gerding,A.Groy, S.Korenchuk,R.Kumar,H.Lei,R.Mook,G.Moorthy,A.Redman,J.Rowland, L.Shewchuk
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Key ref:
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S.D.Chamberlain
et al.
(2009).
Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.
Bioorg Med Chem Lett,
19,
360-364.
PubMed id:
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Date:
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19-Sep-08
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Release date:
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30-Dec-08
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PROCHECK
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Headers
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References
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P06213
(INSR_HUMAN) -
Insulin receptor from Homo sapiens
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Seq:
Struc:
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1382 a.a.
297 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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*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
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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
19:360-364
(2009)
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PubMed id:
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Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.
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S.D.Chamberlain,
A.M.Redman,
J.W.Wilson,
F.Deanda,
J.B.Shotwell,
R.Gerding,
H.Lei,
B.Yang,
K.L.Stevens,
A.M.Hassell,
L.M.Shewchuk,
M.A.Leesnitzer,
J.L.Smith,
P.Sabbatini,
C.Atkins,
A.Groy,
J.L.Rowand,
R.Kumar,
R.A.Mook,
G.Moorthy,
S.Patnaik.
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ABSTRACT
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The SAR of C5' functional groups with terminal basic amines at the C6 aniline of
4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines is reported. Examples demonstrate
potent inhibition of IGF-1R with 1000-fold selectivity over JNK1 and 3 in
enzymatic assays.
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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.Du,
L.Xi,
B.Lei,
H.Liu,
and
X.Yao
(2011).
Structural Requirements of Isoquinolones as Novel Selective c-Jun N-terminal Kinase 1 Inhibitors: 2D and 3D QSAR Analyses.
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Chem Biol Drug Des,
77,
248-254.
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F.Chen,
K.Beezhold,
and
V.Castranova
(2009).
JNK1, a potential therapeutic target for hepatocellular carcinoma.
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Biochim Biophys Acta,
1796,
242-251.
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R.Li,
A.Pourpak,
and
S.W.Morris
(2009).
Inhibition of the insulin-like growth factor-1 receptor (IGF1R) tyrosine kinase as a novel cancer therapy approach.
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J Med Chem,
52,
4981-5004.
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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
