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PDBsum entry 5f95
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Transferase/transferase inhibitor
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PDB id
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5f95
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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 isonicotinamides as highly selective, Brain penetrable, And orally active glycogen synthase kinase-3 inhibitors.
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Authors
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G.Luo,
L.Chen,
C.R.Burton,
H.Xiao,
P.Sivaprakasam,
C.M.Krause,
Y.Cao,
N.Liu,
J.Lippy,
W.J.Clarke,
K.Snow,
J.Raybon,
V.Arora,
M.Pokross,
K.Kish,
H.A.Lewis,
D.R.Langley,
J.E.Macor,
G.M.Dubowchik.
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Ref.
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J Med Chem, 2016,
59,
1041-1051.
[DOI no: ]
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PubMed id
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Abstract
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GSK-3 is a serine/threonine kinase that has numerous substrates. Many of these
proteins are involved in the regulation of diverse cellular functions, including
metabolism, differentiation, proliferation, and apoptosis. Inhibition of GSK-3
may be useful in treating a number of diseases including Alzheimer's disease
(AD), type II diabetes, mood disorders, and some cancers, but the approach poses
significant challenges. Here, we present a class of isonicotinamides that are
potent, highly kinase-selective GSK-3 inhibitors, the members of which
demonstrated oral activity in a triple-transgenic mouse model of AD. The
remarkably high kinase selectivity and straightforward synthesis of these
compounds bode well for their further exploration as tool compounds and
therapeutics.
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