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Bromodomains and Their Pharmacological Inhibitors
Author(s) -
Gallenkamp Daniel,
Gelato Kathy A.,
Haendler Bernard,
Weinmann Hilmar
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300434
Subject(s) - computational biology , bromodomain , pharmacology , medicine , chemistry , biology , biochemistry , epigenetics , gene
Over 60 bromodomains belonging to proteins with very different functions have been identified in humans. Several of them interact with acetylated lysine residues, leading to the recruitment and stabilization of protein complexes. The bromodomain and extra‐terminal domain (BET) proteins contain tandem bromodomains which bind to acetylated histones and are thereby implicated in a number of DNA‐centered processes, including the regulation of gene expression. The recent identification of inhibitors of BET and non‐BET bromodomains is one of the few examples in which effective blockade of a protein–protein interaction can be achieved with a small molecule. This has led to major strides in the understanding of the function of bromodomain‐containing proteins and their involvement in diseases such as cancer and inflammation. Indeed, BET bromodomain inhibitors are now being clinically evaluated for the treatment of hematological tumors and have also been tested in clinical trials for the relatively rare BRD‐NUT midline carcinoma. This review gives an overview of the newest developments in the field, with a focus on the biology of selected bromodomain proteins on the one hand, and on reported pharmacological inhibitors on the other, including recent examples from the patent literature.