Development of novel cellular histone-binding and chromatin-displacement assays for bromodomain drug discovery.

ABSTRACT:

Background

Proteins that 'read' the histone code are central elements in epigenetic control and bromodomains, which bind acetyl-lysine motifs, are increasingly recognized as potential mediators of disease states. Notably, the first BET bromodomain-based therapies have entered clinical trials and there is a broad interest in dissecting the therapeutic relevance of other bromodomain-containing proteins in human disease. Typically, drug development is facilitated and expedited by high-throughput screening, where assays need to be sensitive, robust, cost-effective and scalable. However, for bromodomains, which lack catalytic activity that otherwise can be monitored (using classical enzymology), the development of cell-based, drug-target engagement assays has been challenging. Consequen

SUBMITTER: Zhan Y 

PROVIDER: S-EPMC4578755 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature