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PDBsum entry 5lj0
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Transcription
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PDB id
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5lj0
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References listed in PDB file
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Key reference
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Title
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A chemical probe for the atad2 bromodomain.
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Authors
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P.Bamborough,
C.W.Chung,
E.H.Demont,
R.C.Furze,
A.J.Bannister,
K.H.Che,
H.Diallo,
C.Douault,
P.Grandi,
T.Kouzarides,
A.M.Michon,
D.J.Mitchell,
R.K.Prinjha,
C.Rau,
S.Robson,
R.J.Sheppard,
R.Upton,
R.J.Watson.
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Ref.
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Angew Chem Int Ed Engl, 2016,
55,
11382-11386.
[DOI no: ]
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PubMed id
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Abstract
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ATAD2 is a cancer-associated protein whose bromodomain has been described as
among the least druggable of that target class. Starting from a potent lead,
permeability and selectivity were improved through a dual approach: 1) using CF2
as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2)
using 1,3-interactions to control the conformation of a piperidine ring. This
resulted in the first reported low-nanomolar, selective and cell permeable
chemical probe for ATAD2.
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