a Uniqueness is calculated for the fixed and generated set Applicability on Aurora kinases To compare SMILES-based exploration to an established method for target-directed de novo generation, its applicability for creating new selective AURKB ligands was tested (Table ). Compared to the target-directed RNN, the molecules resulting from SMILES-based exploration were on average more similar to the original compounds. This similarity is comparable to the similarity of the SMILESbased analog generator created by Creanza et al. . The distribution of scaffolds generated by SMILES-based exploration was also more similar to the known ligands. The same trend was reflected by the KL divergence score, indicating that SMILES exploration more closely followed the property distributions of the target dataset. A few of the novel compounds generated based on an original molecule are illustrated in Figure . These findings suggest that SMILES exploration can contribute to de novo generation efforts in which the goal is to design compounds that are more similar to existing ones.