As an initial investigation into the quality of generated compounds, REINVENT-DockStream using Glide with LigPrep against COX2 was performed in triplicate and used as the model experiment to assess the similarity of agent generated compounds to known actives and decoys. The top 150 compounds (based on total score) from each replicate were pooled and duplicates removed, resulting in 298/450 unique compounds, which amounts to about 33% overlap between the individual replicates. The Tanimoto similarities were calculated for each top generated compound compared to each known active (40 total) or decoy (1200 total), as provided in the DEKOIS 2.0 dataset, respectively. The highest Tanimoto similarities were kept, resulting in distributions describing the maximum resemblance of a top generated compound (based on total score) to a known active or known decoy (Fig. ). The prior was trained on the ChEMBL dataset and contains 33/40 and 1/1200 of the known actives and known decoys, respectively. While no actives were recovered, it is evident that the agent generated compounds with notable structural similarity to known actives as measured by a Tanimoto similarity > 0.7 (Fig. ). It follows from Fig. that many of the top compounds contain the sulfonamide moiety which is present in the approved drugs, Celecoxib and Valdecoxib. The maximally similar generated compound displays a Tanimoto similarity of 0.937 and shares both the sulfonamide moiety and the cis-stilbene scaffold with its corresponding known active (Fig. ). In contrast, the highest Tanimoto similarity observed for the most similar decoy to a top generated compound is 0.631 (Fig. ). While the scaffold is shared, the vital sulfonamide moiety is not present. Moreover, the decoy ligands set (1200 total) is 30x larger than the active ligands set (40 total). If the agent policy was not meaningfully updated during the generative process, the likelihood of observing a high Tanimoto similarity (> 0.7) in the decoys set should be increased. Thus, the integration of DockStream with REINVENT facilitates agent convergence to relevant chemical space and the absence of actives recovered does not preclude the generated compounds from being true actives and potentially even more potent. Overall, the absence of Tanimoto similarities above 0.631 amongst the decoys and the presence of Tanimoto similarities > 0.7 amongst the actives suggests the agent is biased towards generating compounds that are more likely to be true