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PDBsum entry 5ml0
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Transcription
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PDB id
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5ml0
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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 a potent, Cell penetrant, And selective p300/cbp-Associated factor (pcaf)/general control nonderepressible 5 (gcn5) bromodomain chemical probe.
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Authors
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P.G.Humphreys,
P.Bamborough,
C.W.Chung,
P.D.Craggs,
L.Gordon,
P.Grandi,
T.G.Hayhow,
J.Hussain,
K.L.Jones,
M.Lindon,
A.M.Michon,
J.F.Renaux,
C.J.Suckling,
D.F.Tough,
R.K.Prinjha.
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Ref.
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J Med Chem, 2017,
60,
695-709.
[DOI no: ]
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PubMed id
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Abstract
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p300/CREB binding protein associated factor (PCAF/KAT2B) and general control
nonderepressible 5 (GCN5/KAT2A) are multidomain proteins that have been
implicated in retroviral infection, inflammation pathways, and cancer
development. However, outside of viral replication, little is known about the
dependence of these effects on the C-terminal bromodomain. Herein, we report
GSK4027 as a chemical probe for the PCAF/GCN5 bromodomain, together with GSK4028
as an enantiomeric negative control. The probe was optimized from a weakly
potent, nonselective pyridazinone hit to deliver high potency for the PCAF/GCN5
bromodomain, high solubility, cellular target engagement, and ≥18000-fold
selectivity over the BET family, together with ≥70-fold selectivity over the
wider bromodomain families.
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