Using the concept SmART (structure multiple-activity relationships), herein we analyze 50 compounds synthesized as dual inhibitors of the enzyme lysine metiltransferase (G9a) and DNA metiltransferase 1 (DNMT1). Both enzymes are epigenetic targets with therapeutic interest for the treatment of hematological neoplastic diseases. The SmART analysis was performed with Structure-Activity Similarity Maps and Dual-Activity Difference maps implemented in the server Activity Landscape Plotter (freely available at www.difacquim.com/d-tools/). Results led to the identification of single target and multi-target activity cliffs. The results where further analyzed at the molecular level using docking and molecular dynamic simulations leading to the identification of structural features that are associated with the dual epigenetic target activity.

Activity landscape modeling and molecular dynamics of dual inhibitors of DNMT1 and G9a

2019 Spring National Meeting

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