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PDBsum entry 2fgi
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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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Crystal structure of the tyrosine kinase domain of fgf receptor 1 in complex with inhibitor pd173074
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Structure:
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Protein (fibroblast growth factor (fgf) receptor 1). Chain: a, b. Fragment: tyrosine kinase domain. Synonym: fgfr1k. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Cell_line: sf9. Cellular_location: cytoplasm. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
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Biol. unit:
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Dimer (from
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Resolution:
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2.50Å
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R-factor:
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0.204
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R-free:
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0.264
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Authors:
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M.Mohammadi,S.Froum,J.M.Hamby,M.Schroeder,R.L.Panek,G.H.Lu, A.V.Eliseenkova,D.Green,J.Schlessinger,S.R.Hubbard
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Key ref:
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M.Mohammadi
et al.
(1998).
Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain.
EMBO J,
17,
5896-5904.
PubMed id:
DOI:
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Date:
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15-Sep-98
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Release date:
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13-Sep-99
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PROCHECK
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Headers
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References
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P11362
(FGFR1_HUMAN) -
Fibroblast growth factor receptor 1 from Homo sapiens
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Seq:
Struc:
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822 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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DOI no:
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EMBO J
17:5896-5904
(1998)
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PubMed id:
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Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain.
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M.Mohammadi,
S.Froum,
J.M.Hamby,
M.C.Schroeder,
R.L.Panek,
G.H.Lu,
A.V.Eliseenkova,
D.Green,
J.Schlessinger,
S.R.Hubbard.
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ABSTRACT
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Angiogenesis, the sprouting of new blood vessels from pre-existing ones, is an
essential physiological process in development, yet also plays a major role in
the progression of human diseases such as diabetic retinopathy, atherosclerosis
and cancer. The effects of the most potent angiogenic factors, vascular
endothelial growth factor (VEGF), angiopoietin and fibroblast growth factor
(FGF) are mediated through cell surface receptors that possess intrinsic protein
tyrosine kinase activity. In this report, we describe a synthetic compound of
the pyrido[2,3-d]pyrimidine class, designated PD 173074, that selectively
inhibits the tyrosine kinase activities of the FGF and VEGF receptors. We show
that systemic administration of PD 173074 in mice can effectively block
angiogenesis induced by either FGF or VEGF with no apparent toxicity. To
elucidate the determinants of selectivity, we have determined the crystal
structure of PD 173074 in complex with the tyrosine kinase domain of FGF
receptor 1 at 2.5 A resolution. A high degree of surface complementarity between
PD 173074 and the hydrophobic, ATP-binding pocket of FGF receptor 1 underlies
the potency and selectivity of this inhibitor. PD 173074 is thus a promising
candidate for a therapeutic angiogenesis inhibitor to be used in the treatment
of cancer and other diseases whose progression is dependent upon new blood
vessel formation.
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Selected figure(s)
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Figure 4.
Figure 4 Mode of PD 173074 binding to FGFR1K. (A) Stereo view of
the PD 173074 binding pocket in FGFR1K. The side chains of
residues that interact with the inhibitor are shown as well as
main-chain atoms that participate in hydrogen bonding.
Split-bond coloring is used with carbon atoms orange (PD 173074)
or green (FGFR1K), oxygen atoms red, nitrogen atoms blue and
sulfur atoms yellow. The FGFR1K main-chain representation is
colored light blue for the nucleotide-binding loop, purple for
the segment connecting the two kinase lobes, yellow for the
catalytic loop and orange for the activation loop. Hydrogen
bonds are shown as dashed lines. (B) Superposition of PD 173074
and AMP-PCP (Mohammadi et al., 1996a) bound to FGFR1K. View is
approximately perpendicular to the
pyrido[2,3-d]pyrimidine/adenine rings. Bonds and carbon atoms
are colored orange (PD 173074), green (FGFR1K) or gray
(AMP-PCP). Other atoms colored as in (A) with phosphorus atoms
black. Hydrogen bonds are shown as black (AMP-PCP) or orange (PD
173074) dashed lines. Due to disorder, the  phosphate
of AMP-PCP is not modeled. Prepared with GRASP (Nicholls et al.,
1991).
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Figure 5.
Figure 5 Schematic diagram of interactions between FGFR1K and PD
173074. Shown are contacts for which the interatomic distance is
 3.8
Å. Thin solid lines denote contacts involving FGFR1K side-chain
atoms, and thin dotted lines denote contacts involving FGFR1K
main-chain atoms. Hydrogen bonds are shown as thick gray lines.
No contacts are shown for the butyl and diethylamino groups due
to the relative disorder of these atoms. Et = ethyl and t-Bu =
tert-butyl.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(1998,
17,
5896-5904)
copyright 1998.
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Figures were
selected
by an automated process.
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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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A.A.Sharov,
A.Nishiyama,
Y.Piao,
L.S.Correa-Cerro,
T.Amano,
M.Thomas,
S.Mehta,
and
M.S.h.Ko
(2011).
Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity.
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BMC Genomics,
12,
102.
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A.R.Ekkati,
V.Madiyan,
K.P.Ravindranathan,
J.H Bae,
J.Schlessinger,
and
W.L.Jorgensen
(2011).
Aryl Extensions of Thienopyrimidinones as Fibroblast Growth Factor Receptor 1 Kinase Inhibitors.
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Tetrahedron Lett,
52,
2228-2231.
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F.R.Lamont,
D.C.Tomlinson,
P.A.Cooper,
S.D.Shnyder,
J.D.Chester,
and
M.A.Knowles
(2011).
Small molecule FGF receptor inhibitors block FGFR-dependent urothelial carcinoma growth in vitro and in vivo.
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Br J Cancer,
104,
75-82.
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J.C.Welti,
M.Gourlaouen,
T.Powles,
S.C.Kudahetti,
P.Wilson,
D.M.Berney,
and
A.R.Reynolds
(2011).
Fibroblast growth factor 2 regulates endothelial cell sensitivity to sunitinib.
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Oncogene,
30,
1183-1193.
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A.J.Firestone,
and
J.K.Chen
(2010).
Controlling destiny through chemistry: small-molecule regulators of cell fate.
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ACS Chem Biol,
5,
15-34.
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C.Pollard,
S.C.Smith,
and
D.Theodorescu
(2010).
Molecular genesis of non-muscle-invasive urothelial carcinoma (NMIUC).
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Expert Rev Mol Med,
12,
e10.
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D.Ellenberg,
D.T.Azar,
J.A.Hallak,
F.Tobaigy,
K.Y.Han,
S.Jain,
Z.Zhou,
and
J.H.Chang
(2010).
Novel aspects of corneal angiogenic and lymphangiogenic privilege.
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Prog Retin Eye Res,
29,
208-248.
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J.Weiss,
M.L.Sos,
D.Seidel,
M.Peifer,
T.Zander,
J.M.Heuckmann,
R.T.Ullrich,
R.Menon,
S.Maier,
A.Soltermann,
H.Moch,
P.Wagener,
F.Fischer,
S.Heynck,
M.Koker,
J.Schöttle,
F.Leenders,
F.Gabler,
I.Dabow,
S.Querings,
L.C.Heukamp,
H.Balke-Want,
S.Ansén,
D.Rauh,
I.Baessmann,
J.Altmüller,
Z.Wainer,
M.Conron,
G.Wright,
P.Russell,
B.Solomon,
E.Brambilla,
C.Brambilla,
P.Lorimier,
S.Sollberg,
O.T.Brustugun,
W.Engel-Riedel,
C.Ludwig,
I.Petersen,
J.Sänger,
J.Clement,
H.Groen,
W.Timens,
H.Sietsma,
E.Thunnissen,
E.Smit,
D.Heideman,
F.Cappuzzo,
C.Ligorio,
S.Damiani,
M.Hallek,
R.Beroukhim,
W.Pao,
B.Klebl,
M.Baumann,
R.Buettner,
K.Ernestus,
E.Stoelben,
J.Wolf,
P.Nürnberg,
S.Perner,
and
R.K.Thomas
(2010).
Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer.
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Sci Transl Med,
2,
62ra93.
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K.P.Ravindranathan,
V.Mandiyan,
A.R.Ekkati,
J.H.Bae,
J.Schlessinger,
and
W.L.Jorgensen
(2010).
Discovery of novel fibroblast growth factor receptor 1 kinase inhibitors by structure-based virtual screening.
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J Med Chem,
53,
1662-1672.
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PDB code:
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L.Le Corre,
A.L.Girard,
J.Aubertin,
F.Radvanyi,
C.Benoist-Lasselin,
A.Jonquoy,
E.Mugniery,
L.Legeai-Mallet,
P.Busca,
and
Y.Le Merrer
(2010).
Synthesis and biological evaluation of a triazole-based library of pyrido[2,3-d]pyrimidines as FGFR3 tyrosine kinase inhibitors.
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Org Biomol Chem,
8,
2164-2173.
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M.A.Canham,
A.A.Sharov,
M.S.Ko,
and
J.M.Brickman
(2010).
Functional heterogeneity of embryonic stem cells revealed through translational amplification of an early endodermal transcript.
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PLoS Biol,
8,
e1000379.
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M.Katoh
(2010).
Genetic alterations of FGF receptors: an emerging field in clinical cancer diagnostics and therapeutics.
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Expert Rev Anticancer Ther,
10,
1375-1379.
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M.P.Stavridis,
B.J.Collins,
and
K.G.Storey
(2010).
Retinoic acid orchestrates fibroblast growth factor signalling to drive embryonic stem cell differentiation.
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Development,
137,
881-890.
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M.Peljto,
J.S.Dasen,
E.O.Mazzoni,
T.M.Jessell,
and
H.Wichterle
(2010).
Functional diversity of ESC-derived motor neuron subtypes revealed through intraspinal transplantation.
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Cell Stem Cell,
7,
355-366.
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N.N.Mott,
W.C.Chung,
P.S.Tsai,
and
T.R.Pak
(2010).
Differential fibroblast growth factor 8 (FGF8)-mediated autoregulation of its cognate receptors, Fgfr1 and Fgfr3, in neuronal cell lines.
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PLoS One,
5,
e10143.
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N.Turner,
M.B.Lambros,
H.M.Horlings,
A.Pearson,
R.Sharpe,
R.Natrajan,
F.C.Geyer,
M.van Kouwenhove,
B.Kreike,
A.Mackay,
A.Ashworth,
M.J.van de Vijver,
and
J.S.Reis-Filho
(2010).
Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets.
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Oncogene,
29,
2013-2023.
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N.Turner,
and
R.Grose
(2010).
Fibroblast growth factor signalling: from development to cancer.
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Nat Rev Cancer,
10,
116-129.
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P.Shi,
S.Nedelec,
H.Wichterle,
and
L.C.Kam
(2010).
Combined microfluidics/protein patterning platform for pharmacological interrogation of axon pathfinding.
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Lab Chip,
10,
1005-1010.
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S.Oki,
K.Kitajima,
and
C.Meno
(2010).
Dissecting the role of Fgf signaling during gastrulation and left-right axis formation in mouse embryos using chemical inhibitors.
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Dev Dyn,
239,
1768-1778.
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S.R.Vora,
A.H.Palamakumbura,
M.Mitsi,
Y.Guo,
N.Pischon,
M.A.Nugent,
and
P.C.Trackman
(2010).
Lysyl oxidase propeptide inhibits FGF-2-induced signaling and proliferation of osteoblasts.
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J Biol Chem,
285,
7384-7393.
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T.Erickson,
C.R.French,
and
A.J.Waskiewicz
(2010).
Meis1 specifies positional information in the retina and tectum to organize the zebrafish visual system.
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Neural Dev,
5,
22.
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W.Zhou,
W.Hur,
U.McDermott,
A.Dutt,
W.Xian,
S.B.Ficarro,
J.Zhang,
S.V.Sharma,
J.Brugge,
M.Meyerson,
J.Settleman,
and
N.S.Gray
(2010).
A structure-guided approach to creating covalent FGFR inhibitors.
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Chem Biol,
17,
285-295.
|
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|
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Z.Sheng,
L.Li,
L.J.Zhu,
T.W.Smith,
A.Demers,
A.H.Ross,
R.P.Moser,
and
M.R.Green
(2010).
A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications.
|
| |
Nat Med,
16,
671-677.
|
|
|
|
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|
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Z.Zheng,
R.U.de Iongh,
P.D.Rathjen,
and
J.Rathjen
(2010).
A requirement for FGF signalling in the formation of primitive streak-like intermediates from primitive ectoderm in culture.
|
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PLoS One,
5,
e12555.
|
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|
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A.Mehanna,
B.Mishra,
N.Kurschat,
C.Schulze,
S.Bian,
G.Loers,
A.Irintchev,
and
M.Schachner
(2009).
Polysialic acid glycomimetics promote myelination and functional recovery after peripheral nerve injury in mice.
|
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Brain,
132,
1449-1462.
|
|
|
|
|
|
|
H.Ning,
G.Liu,
G.Lin,
R.Yang,
T.F.Lue,
and
C.S.Lin
(2009).
Fibroblast growth factor 2 promotes endothelial differentiation of adipose tissue-derived stem cells.
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J Sex Med,
6,
967-979.
|
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J.G.Taylor,
A.T.Cheuk,
P.S.Tsang,
J.Y.Chung,
Y.K.Song,
K.Desai,
Y.Yu,
Q.R.Chen,
K.Shah,
V.Youngblood,
J.Fang,
S.Y.Kim,
C.Yeung,
L.J.Helman,
A.Mendoza,
V.Ngo,
L.M.Staudt,
J.S.Wei,
C.Khanna,
D.Catchpoole,
S.J.Qualman,
S.M.Hewitt,
G.Merlino,
S.J.Chanock,
and
J.Khan
(2009).
Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models.
|
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J Clin Invest,
119,
3395-3407.
|
|
|
|
|
|
|
J.R.Miller,
S.Dunham,
I.Mochalkin,
C.Banotai,
M.Bowman,
S.Buist,
B.Dunkle,
D.Hanna,
H.J.Harwood,
M.D.Huband,
A.Karnovsky,
M.Kuhn,
C.Limberakis,
J.Y.Liu,
S.Mehrens,
W.T.Mueller,
L.Narasimhan,
A.Ogden,
J.Ohren,
J.V.Prasad,
J.A.Shelly,
L.Skerlos,
M.Sulavik,
V.H.Thomas,
S.VanderRoest,
L.Wang,
Z.Wang,
A.Whitton,
T.Zhu,
and
C.K.Stover
(2009).
A class of selective antibacterials derived from a protein kinase inhibitor pharmacophore.
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Proc Natl Acad Sci U S A,
106,
1737-1742.
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PDB codes:
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J.R.St-Germain,
P.Taylor,
J.Tong,
L.L.Jin,
A.Nikolic,
I.I.Stewart,
R.M.Ewing,
M.Dharsee,
Z.Li,
S.Trudel,
and
M.F.Moran
(2009).
Multiple myeloma phosphotyrosine proteomic profile associated with FGFR3 expression, ligand activation, and drug inhibition.
|
| |
Proc Natl Acad Sci U S A,
106,
20127-20132.
|
|
|
|
|
|
|
J.Zhang,
P.L.Yang,
and
N.S.Gray
(2009).
Targeting cancer with small molecule kinase inhibitors.
|
| |
Nat Rev Cancer,
9,
28-39.
|
|
|
|
|
|
|
M.Katoh
(2009).
FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies.
|
| |
J Invest Dermatol,
129,
1861-1867.
|
|
|
|
|
|
|
S.A.Kono,
M.E.Marshall,
K.E.Ware,
and
L.E.Heasley
(2009).
The fibroblast growth factor receptor signaling pathway as a mediator of intrinsic resistance to EGFR-specific tyrosine kinase inhibitors in non-small cell lung cancer.
|
| |
Drug Resist Updat,
12,
95.
|
|
|
|
|
|
|
S.Ota,
Z.Q.Zhou,
J.M.Link,
and
P.J.Hurlin
(2009).
The role of senescence and prosurvival signaling in controlling the oncogenic activity of FGFR2 mutants associated with cancer and birth defects.
|
| |
Hum Mol Genet,
18,
2609-2621.
|
|
|
|
|
|
|
S.Varum,
O.Momcilović,
C.Castro,
A.Ben-Yehudah,
J.Ramalho-Santos,
and
C.S.Navara
(2009).
Enhancement of human embryonic stem cell pluripotency through inhibition of the mitochondrial respiratory chain.
|
| |
Stem Cell Res,
3,
142-156.
|
|
|
|
|
|
|
T.Araki,
G.Chan,
S.Newbigging,
L.Morikawa,
R.T.Bronson,
and
B.G.Neel
(2009).
Noonan syndrome cardiac defects are caused by PTPN11 acting in endocardium to enhance endocardial-mesenchymal transformation.
|
| |
Proc Natl Acad Sci U S A,
106,
4736-4741.
|
|
|
|
|
|
|
W.Loilome,
A.D.Joshi,
C.M.ap Rhys,
S.Piccirillo,
V.L.Angelo,
G.L.Gallia,
and
G.J.Riggins
(2009).
Glioblastoma cell growth is suppressed by disruption of Fibroblast Growth Factor pathway signaling.
|
| |
J Neurooncol,
94,
359-366.
|
|
|
|
|
|
|
A.Dutt,
H.B.Salvesen,
T.H.Chen,
A.H.Ramos,
R.C.Onofrio,
C.Hatton,
R.Nicoletti,
W.Winckler,
R.Grewal,
M.Hanna,
N.Wyhs,
L.Ziaugra,
D.J.Richter,
J.Trovik,
I.B.Engelsen,
I.M.Stefansson,
T.Fennell,
K.Cibulskis,
M.C.Zody,
L.A.Akslen,
S.Gabriel,
K.K.Wong,
W.R.Sellers,
M.Meyerson,
and
H.Greulich
(2008).
Drug-sensitive FGFR2 mutations in endometrial carcinoma.
|
| |
Proc Natl Acad Sci U S A,
105,
8713-8717.
|
|
|
|
|
|
|
B.A.Boswell,
P.A.Overbeek,
and
L.S.Musil
(2008).
Essential role of BMPs in FGF-induced secondary lens fiber differentiation.
|
| |
Dev Biol,
324,
202-212.
|
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|
|
|
|
|
B.A.Boswell,
P.J.Lein,
and
L.S.Musil
(2008).
Cross-talk between fibroblast growth factor and bone morphogenetic proteins regulates gap junction-mediated intercellular communication in lens cells.
|
| |
Mol Biol Cell,
19,
2631-2641.
|
|
|
|
|
|
|
G.M.Morrison,
I.Oikonomopoulou,
R.P.Migueles,
S.Soneji,
A.Livigni,
T.Enver,
and
J.M.Brickman
(2008).
Anterior definitive endoderm from ESCs reveals a role for FGF signaling.
|
| |
Cell Stem Cell,
3,
402-415.
|
|
|
|
|
|
|
M.Tsuchioka,
M.Takebayashi,
K.Hisaoka,
N.Maeda,
and
Y.Nakata
(2008).
Serotonin (5-HT) induces glial cell line-derived neurotrophic factor (GDNF) mRNA expression via the transactivation of fibroblast growth factor receptor 2 (FGFR2) in rat C6 glioma cells.
|
| |
J Neurochem,
106,
244-257.
|
|
|
|
|
|
|
P.M.Jordan,
L.D.Cain,
and
P.Wu
(2008).
Astrocytes enhance long-term survival of cholinergic neurons differentiated from human fetal neural stem cells.
|
| |
J Neurosci Res,
86,
35-47.
|
|
|
|
|
|
|
Q.L.Ying,
J.Wray,
J.Nichols,
L.Batlle-Morera,
B.Doble,
J.Woodgett,
P.Cohen,
and
A.Smith
(2008).
The ground state of embryonic stem cell self-renewal.
|
| |
Nature,
453,
519-523.
|
|
|
|
|
|
|
S.Giulianelli,
J.P.Cerliani,
C.A.Lamb,
V.T.Fabris,
M.C.Bottino,
M.A.Gorostiaga,
V.Novaro,
A.Góngora,
A.Baldi,
A.Molinolo,
and
C.Lanari
(2008).
Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: A role for the FGF-2/FGFR-2 axis.
|
| |
Int J Cancer,
123,
2518-2531.
|
|
|
|
|
|
|
W.Zhang,
Y.Chen,
M.R.Swift,
E.Tassi,
D.C.Stylianou,
K.A.Gibby,
A.T.Riegel,
and
A.Wellstein
(2008).
Effect of FGF-binding Protein 3 on Vascular Permeability.
|
| |
J Biol Chem,
283,
28329-28337.
|
|
|
|
|
|
|
P.Büchler,
H.A.Reber,
M.M.Roth,
M.Shiroishi,
H.Friess,
and
O.J.Hines
(2007).
Target therapy using a small molecule inhibitor against angiogenic receptors in pancreatic cancer.
|
| |
Neoplasia,
9,
119-127.
|
|
|
|
|
|
|
S.F.Winter,
V.D.Acevedo,
R.D.Gangula,
K.W.Freeman,
D.M.Spencer,
and
N.M.Greenberg
(2007).
Conditional activation of FGFR1 in the prostate epithelium induces angiogenesis with concomitant differential regulation of Ang-1 and Ang-2.
|
| |
Oncogene,
26,
4897-4907.
|
|
|
|
|
|
|
C.A.Perlyn,
G.Morriss-Kay,
T.Darvann,
M.Tenenbaum,
and
D.M.Ornitz
(2006).
A model for the pharmacological treatment of crouzon syndrome.
|
| |
Neurosurgery,
59,
210.
|
|
|
|
|
|
|
D.T.Azar
(2006).
Corneal angiogenic privilege: angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an American Ophthalmological Society thesis).
|
| |
Trans Am Ophthalmol Soc,
104,
264-302.
|
|
|
|
|
|
|
L.A.van Grunsven,
V.Taelman,
C.Michiels,
K.Opdecamp,
D.Huylebroeck,
and
E.J.Bellefroid
(2006).
deltaEF1 and SIP1 are differentially expressed and have overlapping activities during Xenopus embryogenesis.
|
| |
Dev Dyn,
235,
1491-1500.
|
|
|
|
|
|
|
L.Derycke,
L.Morbidelli,
M.Ziche,
O.De Wever,
M.Bracke,
and
E.Van Aken
(2006).
Soluble N-cadherin fragment promotes angiogenesis.
|
| |
Clin Exp Metastasis,
23,
187-201.
|
|
|
|
|
|
|
V.P.Eswarakumar,
F.Ozcan,
E.D.Lew,
J.H.Bae,
F.Tomé,
C.J.Booth,
D.J.Adams,
I.Lax,
and
J.Schlessinger
(2006).
Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis.
|
| |
Proc Natl Acad Sci U S A,
103,
18603-18608.
|
|
|
|
|
|
|
D.Moffat,
C.J.Nichols,
D.A.Riley,
and
N.S.Simpkins
(2005).
The synthesis of bioactive indolocarbazoles related to K-252a.
|
| |
Org Biomol Chem,
3,
2953-2975.
|
|
|
|
|
|
|
G.Loers,
S.Chen,
M.Grumet,
and
M.Schachner
(2005).
Signal transduction pathways implicated in neural recognition molecule L1 triggered neuroprotection and neuritogenesis.
|
| |
J Neurochem,
92,
1463-1476.
|
|
|
|
|
|
|
V.P.Eswarakumar,
I.Lax,
and
J.Schlessinger
(2005).
Cellular signaling by fibroblast growth factor receptors.
|
| |
Cytokine Growth Factor Rev,
16,
139-149.
|
|
|
|
|
|
|
X.R.Wu
(2005).
Urothelial tumorigenesis: a tale of divergent pathways.
|
| |
Nat Rev Cancer,
5,
713-725.
|
|
|
|
|
|
|
J.C.Lougheed,
R.H.Chen,
P.Mak,
and
T.J.Stout
(2004).
Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1.
|
| |
J Biol Chem,
279,
44039-44045.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
J.Griffith,
J.Black,
C.Faerman,
L.Swenson,
M.Wynn,
F.Lu,
J.Lippke,
and
K.Saxena
(2004).
The structural basis for autoinhibition of FLT3 by the juxtamembrane domain.
|
| |
Mol Cell,
13,
169-178.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
K.Nakaya
(2004).
[Basic studies for the development of anticancer, antidementia, and taste modifier drugs]
|
| |
Yakugaku Zasshi,
124,
371-396.
|
|
|
|
|
|
|
M.K.Paul,
and
A.K.Mukhopadhyay
(2004).
Tyrosine kinase - Role and significance in Cancer.
|
| |
Int J Med Sci,
1,
101-115.
|
|
|
|
|
|
|
M.Koziczak,
and
N.E.Hynes
(2004).
Cooperation between fibroblast growth factor receptor-4 and ErbB2 in regulation of cyclin D1 translation.
|
| |
J Biol Chem,
279,
50004-50011.
|
|
|
|
|
|
|
Y.Masuda,
G.Shima,
T.Aiuchi,
M.Horie,
K.Hori,
S.Nakajo,
S.Kajimoto,
T.Shibayama-Imazu,
and
K.Nakaya
(2004).
Involvement of tumor necrosis factor receptor-associated protein 1 (TRAP1) in apoptosis induced by beta-hydroxyisovalerylshikonin.
|
| |
J Biol Chem,
279,
42503-42515.
|
|
|
|
|
|
|
A.Facchiano,
K.Russo,
A.M.Facchiano,
F.De Marchis,
F.Facchiano,
D.Ribatti,
M.S.Aguzzi,
and
M.C.Capogrossi
(2003).
Identification of a novel domain of fibroblast growth factor 2 controlling its angiogenic properties.
|
| |
J Biol Chem,
278,
8751-8760.
|
|
|
|
|
|
|
F.D.Böhmer,
L.Karagyozov,
A.Uecker,
H.Serve,
A.Botzki,
S.Mahboobi,
and
S.Dove
(2003).
A single amino acid exchange inverts susceptibility of related receptor tyrosine kinases for the ATP site inhibitor STI-571.
|
| |
J Biol Chem,
278,
5148-5155.
|
|
|
|
|
|
|
G.Bilder,
D.Amin,
L.Morgan,
M.McVey,
S.Needle,
H.Galczenski,
R.Leadley,
W.He,
M.Myers,
A.Spada,
Y.Luo,
C.Natajaran,
and
M.Perrone
(2003).
Stent-induced restenosis in the swine coronary artery is inhibited by a platelet-derived growth factor receptor tyrosine kinase inhibitor, TKI963.
|
| |
J Cardiovasc Pharmacol,
41,
817-829.
|
|
|
|
|
|
|
R.Bansal,
S.Magge,
and
S.Winkler
(2003).
Specific inhibitor of FGF receptor signaling: FGF-2-mediated effects on proliferation, differentiation, and MAPK activation are inhibited by PD173074 in oligodendrocyte-lineage cells.
|
| |
J Neurosci Res,
74,
486-493.
|
|
|
|
|
|
|
G.Williams,
E.J.Williams,
and
P.Doherty
(2002).
Dimeric versions of two short N-cadherin binding motifs (HAVDI and INPISG) function as N-cadherin agonists.
|
| |
J Biol Chem,
277,
4361-4367.
|
|
|
|
|
|
|
J.Adams,
P.Huang,
and
D.Patrick
(2002).
A strategy for the design of multiplex inhibitors for kinase-mediated signalling in angiogenesis.
|
| |
Curr Opin Chem Biol,
6,
486-492.
|
|
|
|
|
|
|
P.De Meyts,
and
J.Whittaker
(2002).
Structural biology of insulin and IGF1 receptors: implications for drug design.
|
| |
Nat Rev Drug Discov,
1,
769-783.
|
|
|
|
|
|
|
P.Stahl,
L.Kissau,
R.Mazitschek,
A.Giannis,
and
H.Waldmann
(2002).
Natural product derived receptor tyrosine kinase inhibitors: identification of IGF1R, Tie-2, and VEGFR-3 inhibitors.
|
| |
Angew Chem Int Ed Engl,
41,
1174-1178.
|
|
|
|
|
|
|
R.A.Engh,
and
D.Bossemeyer
(2002).
Structural aspects of protein kinase control-role of conformational flexibility.
|
| |
Pharmacol Ther,
93,
99.
|
|
|
|
|
|
|
A.Matter
(2001).
Tumor angiogenesis as a therapeutic target.
|
| |
Drug Discov Today,
6,
1005-1024.
|
|
|
|
|
|
|
E.Buchdunger,
A.Matter,
and
B.J.Druker
(2001).
Bcr-Abl inhibition as a modality of CML therapeutics.
|
| |
Biochim Biophys Acta,
1551,
M11-M18.
|
|
|
|
|
|
|
E.J.Williams,
G.Williams,
F.V.Howell,
S.D.Skaper,
F.S.Walsh,
and
P.Doherty
(2001).
Identification of an N-cadherin motif that can interact with the fibroblast growth factor receptor and is required for axonal growth.
|
| |
J Biol Chem,
276,
43879-43886.
|
|
|
|
|
|
|
J.Luo,
P.Guo,
K.Matsuda,
N.Truong,
A.Lee,
C.Chun,
S.Y.Cheng,
and
M.Korc
(2001).
Pancreatic cancer cell-derived vascular endothelial growth factor is biologically active in vitro and enhances tumorigenicity in vivo.
|
| |
Int J Cancer,
92,
361-369.
|
|
|
|
|
|
|
M.Miller,
K.Ginalski,
B.Lesyng,
N.Nakaigawa,
L.Schmidt,
and
B.Zbar
(2001).
Structural basis of oncogenic activation caused by point mutations in the kinase domain of the MET proto-oncogene: modeling studies.
|
| |
Proteins,
44,
32-43.
|
|
|
|
|
|
|
S.Favelyukis,
J.H.Till,
S.R.Hubbard,
and
W.T.Miller
(2001).
Structure and autoregulation of the insulin-like growth factor 1 receptor kinase.
|
| |
Nat Struct Biol,
8,
1058-1063.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
C.García-Echeverría,
P.Traxler,
and
D.B.Evans
(2000).
ATP site-directed competitive and irreversible inhibitors of protein kinases.
|
| |
Med Res Rev,
20,
28-57.
|
|
|
|
|
|
|
J.J.O'Shea,
R.Visconti,
T.P.Cheng,
and
M.Gadina
(2000).
Jaks and stats as therapeutic targets.
|
| |
Ann Rheum Dis,
59,
i115-i118.
|
|
|
|
|
|
|
L.Sun,
and
G.McMahon
(2000).
Inhibition of tumor angiogenesis by synthetic receptor tyrosine kinase inhibitors.
|
| |
Drug Discov Today,
5,
344-353.
|
|
|
|
|
|
|
M.Hagedorn,
and
A.Bikfalvi
(2000).
Target molecules for anti-angiogenic therapy: from basic research to clinical trials.
|
| |
Crit Rev Oncol Hematol,
34,
89.
|
|
|
|
|
|
|
P.Gerwins,
E.Sköldenberg,
and
L.Claesson-Welsh
(2000).
Function of fibroblast growth factors and vascular endothelial growth factors and their receptors in angiogenesis.
|
| |
Crit Rev Oncol Hematol,
34,
185-194.
|
|
|
|
|
|
|
S.D.Skaper,
W.J.Kee,
L.Facci,
G.Macdonald,
P.Doherty,
and
F.S.Walsh
(2000).
The FGFR1 inhibitor PD 173074 selectively and potently antagonizes FGF-2 neurotrophic and neurotropic effects.
|
| |
J Neurochem,
75,
1520-1527.
|
|
|
|
|
|
|
S.R.Hubbard,
and
J.H.Till
(2000).
Protein tyrosine kinase structure and function.
|
| |
Annu Rev Biochem,
69,
373-398.
|
|
|
|
|
|
|
T.Hunter
(2000).
Signaling--2000 and beyond.
|
| |
Cell,
100,
113-127.
|
|
|
|
|
|
|
C.Wiesmann,
and
A.M.de Vos
(1999).
Putting two and two together: crystal structure of the FGF-receptor complex.
|
| |
Structure,
7,
R251-R255.
|
|
|
|
|
|
|
I.Burtscher,
and
G.Christofori
(1999).
The IGF/IGF-1 receptor signaling pathway as a potential target for cancer therapy.
|
| |
Drug Resist Updat,
2,
3-8.
|
|
|
|
|
|
|
J.M.Hamby,
and
H.D.Showalter
(1999).
Small molecule inhibitors of tumor-promoted angiogenesis, including protein tyrosine kinase inhibitors.
|
| |
Pharmacol Ther,
82,
169-193.
|
|
|
|
|
|
|
P.Cohen
(1999).
The development and therapeutic potential of protein kinase inhibitors.
|
| |
Curr Opin Chem Biol,
3,
459-465.
|
|
|
|
|
|
|
T.Schindler,
F.Sicheri,
A.Pico,
A.Gazit,
A.Levitzki,
and
J.Kuriyan
(1999).
Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor.
|
| |
Mol Cell,
3,
639-648.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
W.D.Klohs,
and
J.M.Hamby
(1999).
Antiangiogenic agents.
|
| |
Curr Opin Biotechnol,
10,
544-549.
|
|
|
|
|
|
|
X.Zhu,
J.L.Kim,
J.R.Newcomb,
P.E.Rose,
D.R.Stover,
L.M.Toledo,
H.Zhao,
and
K.A.Morgenstern
(1999).
Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase inhibitors.
|
| |
Structure,
7,
651-661.
|
|
|
PDB codes:
|
|
|
|
|
|
|
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Citation data come partly from CiteXplore and partly
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only a partial list as not all journals are covered by
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so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
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|
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