The phenotype and gene expression in cell does not only depend on the underlying genetic code, but also on a wide range of epigenetic changes. During the last decade, it was realized that the processes responsible for epigenetic control are promising drug targets for the treatment of a wide range of diseases. Modulation of the epigenetic code, which can be thought of as equally important but complementary to the underlying genetic code, by small molecules allows novel approaches to the reprogramming of cells.
The most frequently changed epigenetic code is the acetylation/deacetylation of lysines on histones, which serve as a master regulator of gene expression. In this presentation, nanomolar inhibitors of protein-protein interactions of bromodomains, the “epigenetic readers”, are presented and their application to NUT-midline carcinoma is discussed The role of histone deacetylases, the “epigenetic erasers”, and the design principles for isoform selective inhibitors are discussed. Finally, the application of histone deacetylase inhibitors to the treatment of Niemann-Pick Type C, a fatal neurodegenerative disease, is presented.
Filippakopoulos et al. Nature 2010, 468, 1067; Pipalia et al. Proc. Natl. Acad. Sci. 2011, 108 Early View