Recent advances in DNA-encoded libraries

The DNA-encoded library (DEL), a novel high-throughput screening platform that synergistically combines the strengths of combinatorial chemistry and genetic barcoding, has transitioned from a theoretical framework to a valuable technology within the pharmaceutical research landscape. As an emerging platform for drug discovery, DEL technology has undergone rapid evolution over the past thirty years. This review aims to highlight remarkable advancements in DELs over the past five years across multiple dimensions, including encoding methods, DEL-compatible chemistry, selection methods, library design, and hit picking. It also delves into the issues that have been successfully addressed and the breakthroughs achieved. Finally, this review proposes practical strategies and outlines future research directions that have the potential to further propel the development of DELs in the upcoming five years, aiming to provide valuable insights for drug discovery endeavors.