Synthetic and Medicinal Chemistry Perspectives on Cereblon‐Binding Molecular Glue Degraders: Recent Advances and Emerging Trends

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Authors: Hyuck‐Jae Won, Seung Mok Baek, Min Hoo Lee, Jae Hyeon Park, Jeong‐Won Shin, Yo‐Sep Yang, Y P Jang, Kyung‐Soo Inn, Nam‐Jung Kim
Cited by: 1
References: 75

Abstract

For the past decade, targeted protein degradation (TPD) has emerged as a transformative paradigm in medicinal chemistry and chemical biology. Among the various TPD approaches, cereblon (CRBN)‐recruiting molecular glue degraders (MGDs) have attracted considerable attention due to their favorable drug‐like properties and demonstrated clinical potential. This review provides an overview of recent advances since 2023 in the development of CRBN‐targeting MGDs from synthetic and medicinal chemistry perspectives. We highlight the evolution of novel chemotypes, synthetic strategies, structure–activity relationships (SARs), pharmacological activities, and the mechanistic understanding of ternary complex formation. Finally, we discuss emerging trends and future directions for the discovery and optimization of next‐generation molecular glues.

Fields of Study & Subjects

Protein Degradation and Inhibitors Click Chemistry and Applications Histone Deacetylase Inhibitors Research

Publication details

Journal / source
European Journal of Organic Chemistry
Publisher
Wiley
Volume
29
Issue
17
Publication date
30 March 2026
Language
EN