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Identification of a chemical probe for family VIII bromodomains through optimization of a fragment hit

Abstract:

The acetyl post-translational modification of chromatin at selected histone lysine residues is interpreted by an acetyl-lysine specific interaction with bromodomain reader modules. Here we report the discovery of the potent, acetyl-lysine-competitive, and cell active inhibitor PFI-3 that binds to certain family VIII bromodomains while displaying significant, broader bromodomain family selectivity. The high specificity of PFI-3 for family VIII was achieved through a novel bromodomain binding m...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1021/acs.jmedchem.6b00012

Authors


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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Target Discovery Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Structural Genomics Consortium
Role:
Author
ORCID:
0000-0002-1515-1317
Structural Genomics Consortium More from this funder
National Cancer Institute More from this funder
Publisher:
American Chemical Society Publisher's website
Journal:
Journal of Medicinal Chemistry Journal website
Volume:
59
Issue:
10
Pages:
4800-4811
Publication date:
2016-04-26
Acceptance date:
2016-03-01
DOI:
EISSN:
1520-4804
ISSN:
0022-2623
Pmid:
27115555
Language:
English
Keywords:
Pubs id:
pubs:619363
UUID:
uuid:0871e410-0fe5-4c79-9579-69030fb2409c
Local pid:
pubs:619363
Source identifiers:
619363
Deposit date:
2018-05-22

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