精密工程PROTACs在癌症治疗中最大限度地减少了组织外效应。

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2024-11-22 eCollection Date: 2024-01-01 DOI:10.3389/fmolb.2024.1505255

Jianghua Shi, Luo Wang, Xuanwei Zeng, Chengzhi Xie, Zhaowei Meng, Anahit Campbell, Lulu Wang, Heli Fan, Huabing Sun

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引用次数: 0

摘要

靶向蛋白水解嵌合体（Proteolysis-targeting chimeras, PROTACs）利用泛素-蛋白酶体系统，为选择性降解疾病相关蛋白提供了一种突破性的方法。虽然这种策略在临床前和临床环境中显示出巨大的潜力，但组织外效应仍然是一个主要挑战，导致健康组织中的毒性。本文综述了旨在提高PROTAC特异性的最新进展，包括肿瘤特异性配体导向的PROTAC，在肿瘤环境中激活的pro-PROTACs以及E3连接酶过表达策略。聚乙二醇化和纳米技术等创新也在优化PROTAC功效方面发挥作用。这些发展为更安全、更有效的癌症治疗带来了希望，尽管临床转化仍存在挑战。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Precision-engineered PROTACs minimize off-tissue effects in cancer therapy.

Proteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to selectively degrade disease-related proteins by utilizing the ubiquitin-proteasome system. While this strategy shows great potential in preclinical and clinical settings, off-tissue effects remain a major challenge, leading to toxicity in healthy tissues. This review explores recent advancements aimed at improving PROTAC specificity, including tumor-specific ligand-directed PROTACs, pro-PROTACs activated in tumor environments, and E3 ligase overexpression strategies. Innovations such as PEGylation and nanotechnology also play a role in optimizing PROTAC efficacy. These developments hold promise for safer, more effective cancer therapies, though challenges remain for clinical translation.

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.