Recent Advances in DNA-Encoded Library: High-Throughput Identification of Chemical Inducers of Proximity from Degraders to Non-degraders

DNA编码文库的最新进展:从降解剂到非降解剂的邻近化学诱导剂的高通量鉴定

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Abstract

DNA-encoded library (DEL) technology has emerged as a transformative platform for discovering chemical inducers of proximity (CIPs), addressing challenges in both degrader and non-degrader CIP development. This Microperspective analyzes the results of recent DEL technology screens (2021-2025) to enable medicinal chemistry programs, focusing on CIP development including CIP-focused DELs, DEL-derived ligands for proteins of interest (POIs) and E3 ligase in rational CIP design, and directly functional CIP identification. Finally, we address current limitations of DEL technology in CIP research and outline future directions. This Microperspective underscores DEL's pivotal role in advancing CIP discovery, providing actionable insights for addressing "undruggable" targets and accelerating translational research in chemical biology and medicinal chemistry.

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