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

Journal: Trends in pharmacological sciences
Published Date: May 8, 2025

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.

Authors

  • Yiran Tao
    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.
  • Ying Lu
    Department of Endocrinology, Institute of Translational Medicine, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.
  • Bin Yu
    Department of Anesthesiology, Peking University First Hospital, Ningxia Women's and Children's Hospital, Yinchuan, China.
  • Yuxi Wang
    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.

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