Abstract

Assays and Inhibitors for Targeting the Histone Methylome

Manfred Jung, Chemical Epigenetics Group Leader, Universität Freiburg

Reversible histone methylation is one of the important factors of epigenetic regulation. First inhibitors of histone methyltransferases and demethylases are in clinical trials. For proteins that bind methylated lysines, so called histone code readers, much less is known as compared also to acetyl lysine binding proteins. We present work from our lab on assay development, screening and bioguided inhibitor optimization concerning histone demethylases and methyl lysine readers. Examples are the optimization of chromone based inhibitors of LSD1 (lysine specific demethylase 1) and the identification of novel heterocyclic inhibitors of the demethylase JMJD2A which induce histone hypermethylation and block proliferation of oesophagal cancer cells in culture.