Recent advances in DNA-encoded dynamic libraries.

The DNA-encoded chemical library (DEL) has emerged as a powerful technology platform in drug discovery and is also gaining momentum in academic research. The rapid development of DNA-/DEL-compatible chemistries has greatly expanded the chemical space accessible to DELs. DEL technology has been widely adopted in the pharmaceutical industry and a number of clinical drug candidates have been identified from DEL selections. Recent innovations have combined DELs with other legacy and emerging techniques. Among them, the DNA-encoded dynamic library (DEDL) introduces DNA encoding into the classic dynamic combinatorial libraries (DCLs) and also integrates the principle of fragment-based drug discovery (FBDD), making DEDL a novel approach with distinct features from static DELs. In this Review, we provide a summary of the recently developed DEDL methods and their applications. Future developments in DEDLs are expected to extend the application scope of DELs to complex biological systems with unique ligand-discovery capabilities.