小分子的疏水标记:文献综述与未来展望。

IF 6 2区 医学 Q1 PHARMACOLOGY & PHARMACY Expert Opinion on Drug Discovery Pub Date : 2024-07-01 Epub Date: 2024-06-02 DOI:10.1080/17460441.2024.2360416
Yang Zhou, Fan Zhou, Shujing Xu, Dazhou Shi, Dang Ding, Shuo Wang, Vasanthanathan Poongavanam, Kai Tang, Xinyong Liu, Peng Zhan
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引用次数: 0

摘要

导言:疏水标记(HyT)技术是一种有别于传统小分子药物的独特治疗策略,为药物设计提供了一种创新方法。本综述旨在概述 HyT 文献和未来展望,为药物设计提供指导:在这篇综述中,作者介绍了 HyT 技术的组成、机制和优势,并总结了 HyT 技术在抗癌、神经退行性疾病(NDs)、自身免疫性疾病、心血管疾病(CVDs)等领域的详细应用。此外,本综述还讨论了 HyT 分子未来发展的关键方面:继成功开发蛋白水解靶向嵌合体(PROTAC)和分子胶之后,HyT成为一种极具前景的靶向蛋白质降解(TPD)策略。在探索新途径的基础上,对 HyT 分子本身进行修饰可能会增强这项技术。改进合成途径并重视药代动力学(PK)特性将促进 HyT 的开发。此外,阐明化合物的疏水分子招募蛋白平衡网络的生化基础,将有助于开发更精确的检测方法,从而指导连接体和疏水分子的优化。
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Hydrophobic tagging of small molecules: an overview of the literature and future outlook.

Introduction: Hydrophobic tagging (HyT) technology presents a distinct therapeutic strategy diverging from conventional small molecule drugs, providing an innovative approach to drug design. This review aims to provide an overview of the HyT literature and future outlook to offer guidance for drug design.

Areas covered: In this review, the authors introduce the composition, mechanisms and advantages of HyT technology, as well as summarize the detailed applications of HyT technology in anti-cancer, neurodegenerative diseases (NDs), autoimmune disorders, cardiovascular diseases (CVDs), and other fields. Furthermore, this review discusses key aspects of the future development of HyT molecules.

Expert opinion: HyT emerges as a highly promising targeted protein degradation (TPD) strategy, following the successful development of proteolysis targeting chimeras (PROTAC) and molecular glue. Based on exploring new avenues, modification of the HyT molecule itself potentially enhances the technology. Improved synthetic pathways and emphasis on pharmacokinetic (PK) properties will facilitate the development of HyT. Furthermore, elucidating the biochemical basis by which the compound's hydrophobic moiety recruits the protein homeostasis network will enable the development of more precise assays that can guide the optimization of the linker and hydrophobic moiety.

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来源期刊
CiteScore
10.20
自引率
1.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.
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