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

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.