REVIEW: Targeted Protein Degradation: Methods and Prospects

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Ilya V. Sklyar^1,a*, Aleksandra M. Rozhkova^1,2, Elena G. Kondratyeva^1,2, and Arkadiy P. Sinitsyn^1,2

¹Fundamentals of Biotechnology Federal Research Centre, Russian Academy of Sciences, 119071 Moscow, Russia

²Faculty of Chemistry, Lomonosov Moscow State University, 119992 Moscow, Russia

^* To whom correspondence should be addressed.

Received: August 19, 2025; Revised: September 23, 2025; Accepted: October 9, 2025

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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.

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KEY WORDS: PROTAC, LYTAC, AUTAC, ATTEC, BacPROTAC, AbTAC, Homo-BacPROTAC, AUTOTAC, GlueTAC

DOI: 10.1134/S0006297925604034

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