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Nat Rev Drug Discov. 2014 May;13(5):337-56. doi: 10.1038/nrd4286. Epub 2014 Apr 22.

Targeting bromodomains: epigenetic readers of lysine acetylation.

Author information

1
1] Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. [2] Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7DQ, UK.
2
1] Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. [2] Target Discovery Institute, Nuffield Department of Clinical Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.

Abstract

Lysine acetylation is a key mechanism that regulates chromatin structure; aberrant acetylation levels have been linked to the development of several diseases. Acetyl-lysine modifications create docking sites for bromodomains, which are small interaction modules found on diverse proteins, some of which have a key role in the acetylation-dependent assembly of transcriptional regulator complexes. These complexes can then initiate transcriptional programmes that result in phenotypic changes. The recent discovery of potent and highly specific inhibitors for the BET (bromodomain and extra-terminal) family of bromodomains has stimulated intensive research activity in diverse therapeutic areas, particularly in oncology, where BET proteins regulate the expression of key oncogenes and anti-apoptotic proteins. In addition, targeting BET bromodomains could hold potential for the treatment of inflammation and viral infection. Here, we highlight recent progress in the development of bromodomain inhibitors, and their potential applications in drug discovery.

PMID:
24751816
DOI:
10.1038/nrd4286
[Indexed for MEDLINE]

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