The potential of exploration of the nearby space was also evaluated in terms of the predicted bioactivity and selectivity of the novel compounds generated this way (Figure ). Novel compound 2 has similar predicted bioactivities compared to starting compound 1 (Figure ). Interestingly, novel compound 3 has a lower predicted affinity for AURKB but a slightly higher predicted selectivity. Docking of both compounds in AURKB (PDB 4AF3) shows that they occupy the same region as the cocrystalized ligand (VX-680) with additional stabilizing interactions (Figure and). SMILES exploration resulted in compounds with similar bioactivities to already known compounds, but with a higher density for bioactivities around 6.0 log units, whilst the target-directed RNN was able to produce more compounds with higher predicted activities (Figure ). However, previous studies on derivatization design have suggested that there are also merits to staying closer to known actives, as in the case of this does lead to a higher hit rate compared to a target-directed VAE .