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

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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Publication Details

Journal
ACS Medicinal Chemistry Letters
Published
2026-02-15
DOI
https://doi.org/10.1021/acsmedchemlett.5c00738
Primary Topic
Chemical Synthesis and Analysis
Type
article
Field-Weighted Citation Impact
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article

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

Xiaodong Li, Run Zhou, Yulong An
ACS Medicinal Chemistry Letters
Chemical Synthesis and Analysis
article

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

Xiaodong Li, Run Zhou, Yulong An
article en

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.

ACS Medicinal Chemistry LettersVol. 17(3)
Pharmaceutical Biotechnology (Czechia) (CZ), Zhejiang University (CN), Taizhou University (CN)
Industry, innovation and infrastructure
Openalex Percentile: Top 55%
Chemical Synthesis and Analysis
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