on ChEMBL. This conclusion can be derived from both visualizations generated with PCA and t-SNE. This observation could be related to the scoring function used in alvaBuilder (section 2.2), based on almost the same molecular properties selected for the chemical space visualizations. Five of six properties were also included in the scoring function, only excluding nRotB. The scoring included ESOL and SAscore results and a penalty for substructures commonly found in analog nucleosides. The latter consideration was utterly relevant since the goal is expanding the chemical space of DNMT1 non-nucleoside inhibitors. The properties of the scoring function for alvaBuilder are secondary constraints for the design and could be causing the visualization of all the design libraries to be more compact in the PCA graphs (Figure ). In contrast, the visualizations based on molecular fingerprints, MACCS Keys, and ECFP4 (Figure )