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PDBsum entry 3cqu
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References listed in PDB file
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Key reference
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Title
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Synthesis and structure based optimization of novel akt inhibitors.
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Authors
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B.Lippa,
G.Pan,
M.Corbett,
C.Li,
G.S.Kauffman,
J.Pandit,
S.Robinson,
L.Wei,
E.Kozina,
E.S.Marr,
G.Borzillo,
E.Knauth,
E.G.Barbacci-Tobin,
P.Vincent,
M.Troutman,
D.Baker,
F.Rajamohan,
S.Kakar,
T.Clark,
J.Morris.
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Ref.
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Bioorg Med Chem Lett, 2008,
18,
3359-3363.
[DOI no: ]
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PubMed id
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Abstract
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Based on a high throughput screening hit, pyrrolopyrimidine inhibitors of the
Akt kinase are explored. X-ray co-crystal structures of two lead series results
in the understanding of key binding interactions, the design of new lead series,
and enhanced potency. The syntheses of these series and their biological
activities are described. Spiroindoline 13j is found to have an Akt1 kinase
IC(50) of 2.4+/-0.6 nM, Akt cell potency of 50+/-19 nM, and provides 68%
inhibition of tumor growth in a mouse xenograft model (50 mg/kg, qd, po).
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