Archived and Virtual Libraries Searching. The de novo synthesis of novel scaffolds generated by generative chemistry algorithms remains challenging due to the inherent complexity of these virtual molecules. The complexity, coupled with limitations in scalability and cost-efficiency, poses practical hurdles for the experimental synthesis, even when considering only a subset of these molecules . To address this, we propose an intermediate approach of conducting archived and virtual libraries searching, which can be integrated with high throughput screening directly. This approach involves utilizing existing small molecule libraries, either commercial or those available within the research unit. In our case, we utilized a Novartis internal diverse library containing 3 to 4 million compounds, as well as an external Enamine REAL database with coverage of 4 to 10 billion compounds that can be synthesized on-demand . Another option is the use of a customized enumeration library, referred to as PFL (Project Focus Library), which can be designed based on reaction schemes and building blocks specific to the target of interest .