2. Academic Validation
  3. Recent Advances in Pro-PROTAC Development to Address On-Target Off-Tumor Toxicity

Recent Advances in Pro-PROTAC Development to Address On-Target Off-Tumor Toxicity

  • J Med Chem. 2023 Jul 13;66(13):8428-8440. doi: 10.1021/acs.jmedchem.3c00302.
Chuanjie Chen 1 2,  Yiwen Yang 3,  Zhe Wang 3,  Huiwen Li 1 2,  Chanjuan Dong 1,  Xuan Zhang 1 2 3
Affiliations

Affiliations

  • 1 Drug Discovery & Development Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 2 University of Chinese Academy of Sciences, Beijing 100049, China.
  • 3 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
PMID: 37317568 DOI: 10.1021/acs.jmedchem.3c00302
Abstract

Proteolysis-targeting chimera (PROTAC) technology represents a novel and promising modality for targeted protein degradation with transformative implications for the clinical management of various diseases. Despite notable advantages, the possibility of on-target off-tumor toxicity in healthy cells represents a critical challenge to clinical applications in Cancer treatment. Researchers are currently exploring strategies to enhance targeted degradation activity in a cell-selective manner to minimize undesirable side effects. In this Perspective, we highlight innovative approaches for prodrug-based PROTACs (pro-PROTACs) that facilitate tumor-targeted release. The development of such approaches may further expand the range of potential applications of PROTAC technology within drug development.

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