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PDBsum entry 5cgp
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Transcription/inhibitor
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PDB id
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5cgp
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References listed in PDB file
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Key reference
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Title
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Transcriptional profiling of a selective creb binding protein bromodomain inhibitor highlights therapeutic opportunities.
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Authors
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E.L.Chekler,
J.A.Pellegrino,
T.A.Lanz,
R.A.Denny,
A.C.Flick,
J.Coe,
J.Langille,
A.Basak,
S.Liu,
I.A.Stock,
P.Sahasrabudhe,
P.D.Bonin,
K.Lee,
M.T.Pletcher,
L.H.Jones.
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Ref.
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Chem Biol, 2015,
22,
1588-1596.
[DOI no: ]
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PubMed id
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Abstract
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Bromodomains are involved in transcriptional regulation through the recognition
of acetyl lysine modifications on diverse proteins. Selective pharmacological
modulators of bromodomains are lacking, although the largely hydrophobic nature
of the pocket makes these modules attractive targets for small-molecule
inhibitors. This work describes the structure-based design of a highly selective
inhibitor of the CREB binding protein (CBP) bromodomain and its use in
cell-based transcriptional profiling experiments. The inhibitor downregulated a
number of inflammatory genes in macrophages that were not affected by a
selective BET bromodomain inhibitor. In addition, the CBP bromodomain inhibitor
modulated the mRNA level of the regulator of G-protein signaling 4 (RGS4) gene
in neurons, suggesting a potential therapeutic opportunity for CBP inhibitors in
the treatment of neurological disorders.
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