Targeted Protein Degradation (TPD) for Immunotherapy: Understanding Proteolysis Targeting Chimera-Driven Ubiquitin-Proteasome Interactions

被引：3

作者：

Kamaraj, Rajamanikkam ^{[1
]}

Ghosh, Subhrojyoti ^{[2
]}

Das, Souvadra ^{[3
]}

Sen, Shinjini ^{[3
]}

Kumar, Priyanka ^{[3
]}

Majumdar, Madhurima ^{[3
]}

Dasgupta, Renesa ^{[3
]}

Mukherjee, Sampurna ^{[3
]}

Das, Shrimanti ^{[3
]}

Ghose, Indrilla ^{[3
]}

Pavek, Petr ^{[1
]}

Karuppiah, Muruga Poopathi Raja ^{[4
]}

Chuturgoon, Anil A. ^{[5
]}

Anand, Krishnan ^{[6
]}

机构：

[1] Charles Univ Prague, Fac Pharm, Dept Pharmacol & Toxicol, Hradec Kralove 50005, Czech Republic

[2] Indian Inst Technol Madras, Dept Biotechnol, Chennai 600036, India

[3] Heritage Inst Technol, Dept Biotechnol, Kolkata 700107, India

[4] Cent Univ Kerala, Sch Phys Sci, Dept Chem, Periye 671320, Kerala, India

[5] Univ KwaZulu Natal, Coll Hlth Sci, Discipline Med Biochem, Sch Lab Med & Med Sci, Howard Coll Campus, ZA-4041 Durban, South Africa

[6] Univ Free State, Fac Hlth Sci, Sch Pathol, Dept Chem Pathol, ZA-9300 Bloemfontein, Free State, South Africa

来源：

BIOCONJUGATE CHEMISTRY | 2024年 / 35卷 / 08期

基金：

新加坡国家研究基金会;

关键词：

CANCER-IMMUNOTHERAPY; TYROSINE KINASE; PROTAC DEGRADER; CELL-ACTIVATION; ACHIEVES SAFE; POTENT; SYSTEM; STAT3; IDENTIFICATION; BROMODOMAIN;

D O I：

10.1021/acs.bioconjchem.4c00253

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Targeted protein degradation or TPD, is rapidly emerging as a treatment that utilizes small molecules to degrade proteins that cause diseases. TPD allows for the selective removal of disease-causing proteins, including proteasome-mediated degradation, lysosome-mediated degradation, and autophagy-mediated degradation. This approach has shown great promise in preclinical studies and is now being translated to treat numerous diseases, including neurodegenerative diseases, infectious diseases, and cancer. This review discusses the latest advances in TPD and its potential as a new chemical modality for immunotherapy, with a special focus on the innovative applications and cutting-edge research of PROTACs (Proteolysis TArgeting Chimeras) and their efficient translation from scientific discovery to technological achievements. Our review also addresses the significant obstacles and potential prospects in this domain, while also offering insights into the future of TPD for immunotherapeutic applications.

引用

页码：1089 / 1115

页数：27

共 5 条

[1] Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy
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[2] Chemically induced degradation of CK2 by proteolysis targeting chimeras based on a ubiquitin-proteasome pathway
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[4] Intracellular protein degradation: From a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting
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[5] Self-Assembled Peptide-Derived Proteolysis-Targeting Chimera (PROTAC) Nanoparticles for Tumor-Targeted and Durable PD-L1 Degradation in Cancer Immunotherapy
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ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2025, 64 (05)

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