Discovery of Histone Demethylase Inhibitors

The main biochemical epigenetic mechanisms are DNA methylation and posttranslational modifications of histone proteins. Among the histone modifications, in recent years the reversible methylation of lysine residues has emerged as one of the most important mechanisms of epigenetic regulation, especially with regard to drug discovery. This chapter gives an overview of the different types of histone demethylating enzymes and highlights key findings as to their role in the development of certain diseases. We will explain the strategies that led to the discovery and characterization of available histone demethylase inhibitors and present structural aspects of inhibitor binding.