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PDBsum entry 3l9l
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Transferase/transferase inhibitor
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PDB id
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3l9l
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References listed in PDB file
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Key reference
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Title
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Azole-Based inhibitors of akt/pkb for the treatment of cancer.
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Authors
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Q.Zeng,
J.G.Allen,
M.P.Bourbeau,
X.Wang,
G.Yao,
S.Tadesse,
J.T.Rider,
C.C.Yuan,
F.T.Hong,
M.R.Lee,
S.Zhang,
J.A.Lofgren,
D.J.Freeman,
S.Yang,
C.Li,
E.Tominey,
X.Huang,
D.Hoffman,
H.K.Yamane,
C.Fotsch,
C.Dominguez,
R.Hungate,
X.Zhang.
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Ref.
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Bioorg Med Chem Lett, 2010,
20,
1559-1564.
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PubMed id
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Abstract
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Through a combination of screening and structure-based rational design, we have
discovered a series of
N(1)-(5-(heterocyclyl)-thiazol-2-yl)-3-(4-trifluoromethylphenyl)-1,2-propanediamines
that were developed into potent ATP competitive inhibitors of AKT. Studies of
linker strand-binding adenine isosteres identified SAR trends in potency and
selectivity that were consistent with binding interactions observed in
structures of the inhibitors bound to AKT1 and to the counter-screening target
PKA. One compound was shown to have acceptable pharmacokinetic properties and to
be a potent inhibitor of AKT signaling and of in vivo xenograft tumor growth in
a preclinical model of glioblastoma.
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