Approximately 16-30% of de novo molecules per experiment contain commercially novel molecules containing known target chemotypes which are therefore of immediate interest from a practical drug discovery perspective. This enrichment in high scoring, desirable compounds led to a hit rate of 88% (8/9) based on binding. This hit rate is higher than previously reported virtual screening efforts in the hunt for A 2A ligands which were between 3% and 64% . This is a considerable improvement especially given that identifying novel A 2A ligands is increasingly difficult due to exhaustive exploration of A 2A ligand chemical space in the scientific domain. This is highlighted by Lenselink et active molecules out of 71 selected when enforcing high degrees of novelty . Moreover, this workflow is practical to implement with each experiment taking 5.94 hours on average using a single consumer grade GPU (here an NVIDIA RTX 2080Ti) and parallelised over approximately 30 CPUs; therefore, possible to complete overnight.