Virtual screening 1 plays a crucial role in this process due to its ability to rapidly and costeffectively determine which compounds are worthy of further experimental synthesis and testing. Traditionally, virtual screening has been performed on in-stock libraries, which typically contain several million compounds with limited chemical diversity and novelty. However, advances in computer hardware and software have enabled the generation and use of ultra-large virtual chemical spaces, comprising billions of previously unexplored compounds. Importantly, these spaces are constructed from available building blocks based on robust chemical reactions, thus ensuring high synthetic success rates.