Epigenetic Drug Discovery

The molecular aetiology of disease relies on a complex interplay between our underlying genetic predispositions and the more dynamic epigenetic signatures that govern how our DNA is transcribed. Whilst there is no opportunity to alter the genome with which we are born, there may be potential to understand, modulate and reset aberrant epigenetic motifs that lie at the root of dysfunction and thereby restore health. Small molecule inhibitors of epigenetic proteins such as the ‘writers’, ‘erasers’ and ‘readers’ of histone post-translational modifications provide chemical tools to assist our biological understanding and offer the prospect of epigenetic drugs that may give distinct and profound pharmacology in a number of complex diseases. This article introduces the proteins involved in histone epigenetic gene regulation and highlights the potential of diverse drug discovery approaches to deliver chemical tools and clinical candidates for Jumonji demethylase enzymes and bromodomain reader proteins.