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PDBsum entry 3v5q
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Transferase/transferase inhibitor
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PDB id
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3v5q
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References listed in PDB file
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Key reference
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Title
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Discovery of gnf-5837, A selective trk inhibitor with efficacy in rodent cancer tumor models.
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Authors
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P.Albaugh,
Y.Fan,
Y.Mi,
F.Sun,
F.Adrian,
N.Li,
Y.Jia,
Y.Sarkisova,
A.Kreusch,
T.Hood,
M.Lu,
G.Liu,
S.Huang,
Z.Liu,
J.Loren,
T.Tuntland,
D.S.Karanewsky,
H.M.Seidel,
V.Molteni.
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Ref.
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ACS Med Chem Lett, 2012,
3,
140-145.
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PubMed id
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Abstract
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Neurotrophins and their receptors (TRKs) play key roles in the development of
the nervous system and the maintenance of the neural network. Accumulating
evidence points to their role in malignant transformations, chemotaxis,
metastasis, and survival signaling and may contribute to the pathogenesis of a
variety of tumors of both neural and non-neural origin. By screening the GNF
kinase collection, a series of novel oxindole inhibitors of TRKs were
identified. Optimization led to the identification of GNF-5837 (22), a potent,
selective, and orally bioavailable pan-TRK inhibitor that inhibited tumor growth
in a mouse xenograft model derived from RIE cells expressing both TRKA and NGF.
The properties of 22 make it a good tool for the elucidation of TRK biology in
cancer and other nononcology indications.
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