In order to filter for unwanted substructures, we extracted known toxic substructures from a published collection by SureChEMBL . Moreover, to filter for possible unstable structures we created a list with extended-connectivity fingerprints (ECFP4) of substructures that occur in more than 5 individual compounds in ChEMBL. During the optimization, generated structures are penalized if they contain such known toxic substructures or have uncommon ECFP4 bits.