Generating automatically and consistently the main scaffold or core structure of large data sets can be done in several ways as recently reviewed. In general, it is desirable to generate the scaffolds rapidly, consistently, and interpretable, in particular for an organic or medicinal chemist working on chemical synthesis. As detailed in the Methods section, in this work we implemented two methodologies generating the Bemis-Murcko scaffolds and analog series based on core scaffolds (Figure ). Concerning the core scaffolds and analog series, the most frequent are shown in Figure . The obtained cores overlap very little with the 201 substructures that have been annotated as epigenetic bioactive rings in a recent publication: of the 4016 cores matching at least three molecules from any epigenetic data set, only 19 contained at least one of the epigenetic rings. This highlights the structural novelty of the studied libraries and it's potential to expand the epigenetic relevant chemical space.