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  3. Molecular glue meets antibody: next-generation antibody-drug conjugates

Molecular glue meets antibody: next-generation antibody-drug conjugates

  • Trends Pharmacol Sci. 2025 Jun;46(6):520-534. doi: 10.1016/j.tips.2025.04.002.
Yiran Tao 1,  Ying Lu 1,  Bin Yu 2,  Yuxi Wang 3
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 2 Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, College of Chemistry, Zhengzhou University, Zhengzhou 450001, China. Electronic address: yubin@zzu.edu.cn.
  • 3 Department of Pulmonary and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China; Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, 610093, Sichuan, China. Electronic address: yuxiwang@scu.edu.cn.
PMID: 40345868 DOI: 10.1016/j.tips.2025.04.002
Abstract

Antibody-drug conjugates (ADCs) have revolutionized oncology by enabling the delivery of cytotoxic agents. However, persistent limitations in payload diversity and emerging drug-resistance mechanisms have spurred investigations into innovative payload modalities. Molecular glue-antibody conjugates (MACs), which utilize Molecular Glues as payloads, represent a groundbreaking advance in this field. By leveraging the catalytic, event-driven nature of Molecular Glues, MACs offer enhanced efficacy, reduced off-target effects, and an improved therapeutic index. Two MACs are now in clinical trials. This review explores MAC mechanisms, advances, and potential to surpass traditional ADCs and Molecular Glues, while addressing development challenges and future directions.

Keywords

antibody–drug conjugate; artificial intelligence; molecular glue; molecular glue–antibody conjugate; targeted protein degradation.

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