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Abstract <p>In recent years, targeted proteolysis systems have emerged as powerful tools for directed degradation of pathogenic proteins, offering novel therapeutic strategies for cancer, neurodegenerative disorders, and infectious diseases. This review systematizes key mechanisms and recent advances in inducible targeted proteolysis, including targeted proteasomal degradation (PROTACs, AbTACs, molecular glues), lysosome-mediated degradation (LYTACs, AUTACs, ATTECs) via endocytosis or autophagy, and targeted proteolysis in bacteria (BacPROTACs), which extends degradation technologies to prokaryotic systems. The structural features, advantages, and limitations of each platform are discussed in detail, along with key publications demonstrating their preclinical and clinical efficacy. Special attention is given to the prospects for translating these technologies into therapeutics, including overcoming challenges such as selectivity and <i>in&#xa0;vivo</i> delivery.</p>

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Targeted Protein Degradation: Methods and Prospects

  • 期刊论文

  • 发表日期：

    2026年2月1日

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  • Ilya V. Sklyar,
  • Aleksandra M. Rozhkova,
  • Elena G. Kondratyeva,
  • Arkadiy P. Sinitsyn

摘要

Abstract

In recent years, targeted proteolysis systems have emerged as powerful tools for directed degradation of pathogenic proteins, offering novel therapeutic strategies for cancer, neurodegenerative disorders, and infectious diseases. This review systematizes key mechanisms and recent advances in inducible targeted proteolysis, including targeted proteasomal degradation (PROTACs, AbTACs, molecular glues), lysosome-mediated degradation (LYTACs, AUTACs, ATTECs) via endocytosis or autophagy, and targeted proteolysis in bacteria (BacPROTACs), which extends degradation technologies to prokaryotic systems. The structural features, advantages, and limitations of each platform are discussed in detail, along with key publications demonstrating their preclinical and clinical efficacy. Special attention is given to the prospects for translating these technologies into therapeutics, including overcoming challenges such as selectivity and in vivo delivery.