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寻找正确药物靶点的艺术:新兴方法和策略。

The Art of Finding the Right Drug Target: Emerging Methods and Strategies.

机构信息

State Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang, China (Z.-C.J., X.Y., Y.-K.W., M.-X.C., J.W.); The Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee (D.D.); and State Key Laboratory of Crop Biology, College of Life Science, Shandong Agricultural University, Taian, Shandong, China (M.L.).

State Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang, China (Z.-C.J., X.Y., Y.-K.W., M.-X.C., J.W.); The Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee (D.D.); and State Key Laboratory of Crop Biology, College of Life Science, Shandong Agricultural University, Taian, Shandong, China (M.L.)

出版信息

Pharmacol Rev. 2024 Aug 15;76(5):896-914. doi: 10.1124/pharmrev.123.001028.

Abstract

Drug targets are specific molecules in biological tissues and body fluids that interact with drugs. Drug target discovery is a key component of drug discovery and is essential for the development of new drugs in areas such as cancer therapy and precision medicine. Traditional in vitro or in vivo target discovery methods are time-consuming and labor-intensive, limiting the pace of drug discovery. With the development of modern discovery methods, the discovery and application of various emerging technologies have greatly improved the efficiency of drug discovery, shortened the cycle time, and reduced the cost. This review provides a comprehensive overview of various emerging drug target discovery strategies, including computer-assisted approaches, drug affinity response target stability, multiomics analysis, gene editing, and nonsense-mediated mRNA degradation, and discusses the effectiveness and limitations of the various approaches, as well as their application in real cases. Through the review of the aforementioned contents, a general overview of the development of novel drug targets and disease treatment strategies will be provided, and a theoretical basis will be provided for those who are engaged in pharmaceutical science research. SIGNIFICANCE STATEMENT: Target-based drug discovery has been the main approach to drug discovery in the pharmaceutical industry for the past three decades. Traditional drug target discovery methods based on in vivo or in vitro validation are time-consuming and costly, greatly limiting the development of new drugs. Therefore, the development and selection of new methods in the drug target discovery process is crucial.

摘要

药物靶点是生物组织和体液中与药物相互作用的特定分子。药物靶点发现是药物发现的关键组成部分,对于癌症治疗和精准医学等领域的新药开发至关重要。传统的体外或体内靶点发现方法既耗时又费力,限制了药物发现的速度。随着现代发现方法的发展,各种新兴技术的发现和应用极大地提高了药物发现的效率,缩短了周期时间,降低了成本。本综述全面概述了各种新兴的药物靶点发现策略,包括计算机辅助方法、药物亲和力反应靶标稳定性、多组学分析、基因编辑和无义介导的 mRNA 降解,并讨论了各种方法的有效性和局限性,以及它们在实际案例中的应用。通过对上述内容的综述,将提供对新型药物靶点和疾病治疗策略发展的全面概述,并为从事药物科学研究的人员提供理论依据。

意义陈述:基于靶点的药物发现一直是过去三十年来制药行业药物发现的主要方法。基于体内或体外验证的传统药物靶点发现方法既耗时又昂贵,极大地限制了新药的开发。因此,在药物靶点发现过程中开发和选择新方法至关重要。

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