Targeting bromodomains: epigenetic readers of lysine acetylation - PubMed (original) (raw)

Review

doi: 10.1038/nrd4286. Epub 2014 Apr 22.

Affiliations

Review

Targeting bromodomains: epigenetic readers of lysine acetylation

Panagis Filippakopoulos et al. Nat Rev Drug Discov. 2014 May.

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.

PubMed Disclaimer

Similar articles

Cited by

References

    1. ACS Med Chem Lett. 2013 Jul 16;4(9):835-40 - PubMed
    1. Oncogene. 2014 May 1;33(18):2395-404 - PubMed
    1. Nat Rev Cancer. 2012 Jun 22;12(7):465-77 - PubMed
    1. Cell. 2007 Feb 23;128(4):693-705 - PubMed
    1. Blood. 2014 Jan 30;123(5):697-705 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources