DNA-Encoded Libraries for Drug Discovery:

Division/Committee: [MEDI: Division of Medicinal Chemistry]

DNA-encoded libraries (DELs) have emerged as a powerful screening tool for hit identification and offer distinct advantages over traditional high-throughput screening libraries. DEL libraries are typically synthesized on an enormous scale via split-and-pool combinatorial synthesis from a growing number of commercial building blocks and can contain hundreds of millions up to billions of molecules. Additionally, DELs can be screened against the protein of interest in a single experiment. This enables a rapid assessment of druggability as it is possible to explore multiple selections in parallel, such as against multiple targets to prioritize selectivity, or with different protein constructs and/or selection conditions to screen for different modes of action. With the steady advances in DEL design and screening technologies, along with the large data sets generated and the increasing power of data and AI/ML, DEL approaches have become increasingly impactful as a lead-finding strategy. This symposium will present recent success stories with details on how novel ligands were isolated (selecting the most viable drug candidate) from encoded library screenings and further optimized by medicinal chemistry. Encoded libraries for a wider range of targets (including reversible and irreversible DEL selection approaches) and DNA-tagged small molecule building blocks that represent diverse scaffolds are also key focus areas of advancements in the field. The most recent developments will be presented by state-of-the-art speakers in the field, while also elaborating on future challenges aimed at enhancing the technology as a platform for therapeutic discovery.