Georgetown University, Washington, DC, USA; Arkuda Therapeutics, Watertown, MA, USA.
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Drug Discov Today. 2023 Oct;28(10):103751. doi: 10.1016/j.drudis.2023.103751. Epub 2023 Aug 26.
Metabolomics and lipidomics have an increasingly pivotal role in drug discovery and development. In the context of drug discovery, monitoring changes in the levels or composition of metabolites and lipids relative to genetic variations yields functional insights, bolstering human genetics and (meta)genomic methodologies. This approach also sheds light on potential novel targets for therapeutic intervention. In the context of drug development, metabolite and lipid biomarkers contribute to enhanced success rates, promising a transformative impact on precision medicine. In this review, we deviate from analytical chemist-focused perspectives, offering an overview tailored to drug discovery. We provide introductory insight into state-of-the-art mass spectrometry (MS)-based metabolomics and lipidomics techniques utilized in drug discovery and development, drawing from the collective expertise of our research teams. We comprehensively outline the application of metabolomics and lipidomics in advancing drug discovery and development, spanning fundamental research, target identification, mechanisms of action, and the exploration of biomarkers.
代谢组学和脂质组学在药物发现和开发中发挥着越来越关键的作用。在药物发现方面，监测与遗传变异相关的代谢物和脂质水平或组成的变化，可以提供功能见解，增强人类遗传学和（宏）基因组学方法。这种方法还揭示了治疗干预的潜在新靶点。在药物开发方面，代谢物和脂质生物标志物有助于提高成功率，有望对精准医学产生变革性影响。在这篇综述中，我们偏离了以分析化学家为重点的观点，提供了一个针对药物发现的概述。我们从我们的研究团队的集体专业知识中汲取了最新的基于质谱 (MS) 的代谢组学和脂质组学技术，为您提供入门级的见解。我们全面概述了代谢组学和脂质组学在推进药物发现和开发中的应用，涵盖了基础研究、靶点鉴定、作用机制以及生物标志物的探索。
