从化学诱导的蛋白质相互作用中产生惊人的强大药理学。

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2025-07-24 DOI:10.1021/acs.accounts.5c00225

Stephen M Hinshaw,Steven M Banik,Nathanael S Gray

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引用次数: 0

摘要

诱导蛋白质之间接近的小分子改变了我们操纵和研究细胞过程的能力。除此之外，邻近诱导小分子和生物制剂现在已经成为临床现实，越来越多地涉及不同的目标和疾病适应症，受益于我们快速扩展的利用各种生化机制的能力，并受到新兴设计原则的推动。靶向蛋白降解已成为主要的邻近依赖性治疗机制。我们认为，化学诱导的蛋白质相互作用可以触发许多尚未探索的药理学有用机制。我们讨论了接近药理学的一般原则，并强调了两个我们认为成熟的创新领域。

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Generating Surprisingly Powerful Pharmacology from Chemically Induced Protein Interactions.

ConspectusSmall molecules that induce proximity between proteins have transformed our ability to manipulate and study cellular processes. Beyond this, proximity-inducing small molecules and biologics are now a clinical reality with increasing reach over different targets and disease indications, benefiting from our rapidly expanding abilities to exploit diverse biochemical mechanisms and being powered by emerging design principles. Targeted protein degradation has become a predominant proximity-dependent therapeutic mechanism. We contend that there are many yet-unexplored pharmacologically useful mechanisms that can be triggered by chemically induced protein interactions. We discuss the general principles of proximity pharmacology and highlight two areas we believe are ripe for innovation.

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.