Abstract

Chemical Biology Tools for Target Identification and Validation

Kilian Huber, Principal Investigator and Chemical Biology Group Leader, University of Oxford

Histone acetylation represents a key mechanism to regulate gene expression in response to external stimuli. This posttranslational modification can be recognised by epigenetic readers such as bromodomain-containing proteins which in turn recruit additional factors to drive transcription. Several studies over the past years have demonstrated that disruption of the bromodomain-chromatin interaction by e.g. BET inhibitors leads to strong phenotypes in disease model systems highlighting these proteins as interesting and tractable target candidates for drug discovery. In order to facilitate their further evaluation as potential drug targets the Structural Genomics Consortium (SGC) and its academic and industrial partners have been working towards establishing a set of small molecule tool compounds, also referred to as chemical probes, to enable functional cellular studies complementary to genetic approaches to further study bromodomain-containing proteins and their relevance for human disease. This talk will provide an update on the recent efforts to develop selective chemical probes for this target class.