基于块化学的分子胶水降解剂的合理发现。

IF 7.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Discovery Today Pub Date : 2025-09-20 DOI:10.1016/j.drudis.2025.104480

Junjie Wei , Wenjing Feng , Qingsong Chen , Qianbin Li , Zhuo Chen

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引用次数: 0

摘要

分子胶降解剂（MGDs）作为一种有前景的治疗药物，在其药物开发方面具有巨大的临床潜力和日益增长的商业兴趣。然而，将MGDs转化为临床试验仍然有限。药物发现技术的最新进展正在促进MGD发展的范式转变，从偶然发现到理性设计。在此，我们系统地分析了合理的MGD发现策略，重点是E3连接酶和靶配体修饰。此外，我们还重点介绍了MGD发展的前沿技术和最新趋势。因此，本综述为研究人员提供了有价值的见解，并有助于加速MGDs的临床转化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Rational discovery of molecular glue degraders based on block chemistry

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Rational discovery of molecular glue degraders based on block chemistry

Molecular glue degraders (MGDs) have emerged as promising therapeutic agents with substantial clinical potential and growing commercial interest in terms of their pharmaceutical development. Nevertheless, the translation of MGDs into clinical trials remains limited. Recent advances in drug discovery technologies are facilitating a paradigm shift in MGD development, from serendipitous discovery to rational design. Here, we systematically analyze rational MGD discovery strategies, focusing on E3 ligase and target ligand modifications. Furthermore, we highlight cutting-edge technologies and the latest trends in MGD development. Thus, this review provide valuable insights for researchers and could help accelerate the clinical translation of MGDs.

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来源期刊

Drug Discovery Today 医学-药学

CiteScore

14.80

自引率

2.70%

发文量

293

审稿时长

6 months

期刊介绍： Drug Discovery Today delivers informed and highly current reviews for the discovery community. The magazine addresses not only the rapid scientific developments in drug discovery associated technologies but also the management, commercial and regulatory issues that increasingly play a part in how R&D is planned, structured and executed. Features include comment by international experts, news and analysis of important developments, reviews of key scientific and strategic issues, overviews of recent progress in specific therapeutic areas and conference reports.