PROTAC 可控性技术的研究进展。

Progress in the controllability technology of PROTAC.

机构信息

School of Chemical and Pharmaceutical Engineering, Changzhou Vocational Institute of Engineering, Changzhou, 213164, PR China.

出版信息

Eur J Med Chem. 2024 Feb 5;265:116096. doi: 10.1016/j.ejmech.2023.116096. Epub 2023 Dec 27.

DOI:10.1016/j.ejmech.2023.116096

PMID:38160619

Abstract

Proteolysis-targeting chimaera (PROTAC) technology functions by directly targeting proteins and catalysing their degradation through an event-driven mode of action, a novel mechanism with significant clinical application prospects for various diseases. Currently, the most advanced PROTAC drug is undergoing phase III clinical trials (NCT05654623). Although PROTACs exhibit significant advantages over traditional small-molecule inhibitors, their catalytic degradation of normal cellular proteins can potentially cause toxic side effects. Therefore, to achieve targeted release of PROTACs and minimize adverse reactions, researchers are actively exploring diverse controllable PROTACs. In this review, we comprehensively summarize the control strategies to provide a theoretical basis for the innovative application of PROTAC technology.

摘要

蛋白水解靶向嵌合体（PROTAC）技术通过直接靶向蛋白质并通过事件驱动的作用模式催化其降解，为各种疾病提供了一种具有重要临床应用前景的新型机制。目前，最先进的 PROTAC 药物正在进行 III 期临床试验（NCT05654623）。尽管 PROTAC 相对于传统的小分子抑制剂具有显著优势，但它们对正常细胞蛋白的催化降解可能会导致毒性副作用。因此，为了实现 PROTAC 的靶向释放并最小化不良反应，研究人员正在积极探索各种可控的 PROTAC。在这篇综述中，我们全面总结了控制策略，为 PROTAC 技术的创新应用提供了理论基础。