Insights from pharmacological similarity of epigenetic targets in epipolypharmacology.

As the number of compounds tested against epigenetic targets grows, exploration of the possible associations in chemical space among these targets could lead to the identification of new drugs or new designs of epipolypharmacological molecules. Thus, here we review compound-epitarget associations of public databases. Specifically, we explore the structure-multitarget activity relationships and diversity of over 7000 compounds tested against 52 epigenetic-related targets. We found that, whereas inhibitors of histone deacetylases and other epigenetic targets are clustered in the chemical space, the chemical space of inhibitors of different DNA methyltransferases (DNMTs) did not overlap, indicating DNMT selectivity. These and other compound-epitarget relationships discussed here could be useful for both drug repurposing and the rational design of epipolypharmacological compounds.