Wang Yixin, Wang Fan, Liu Wenxiu, Geng Yifei, Shi Yahong, Tian Yu, Zhang Bin, Luo Yun, Sun Xiaobo
Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China.
Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China.
Pharmacol Ther. 2024 Dec;264:108752. doi: 10.1016/j.pharmthera.2024.108752. Epub 2024 Nov 16.
Natural products (NPs) have a long history as sources for drug discovery, more than half of approved drugs are related to NPs, which also exhibit multifaceted advantages in the clinical treatment of complex diseases. However, bioactivity screening of NPs, target identification, and design optimization require continuously improved strategies, the complexity of drug mechanism of action and the limitations of technological strategies pose numerous challenges to the development of new drugs. This review begins with an overview of bioactivity- and target-based drug development patterns for NPs, advances in NP screening and derivatization, and the advantages and problems of major targets such as genes and proteins. Then, target-based drugs as well as identification and validation methods are further discussed to elucidate their mechanism of action. Subsequently, the current status and development trend of the application of traditional and emerging technologies in drug discovery and development of NPs are systematically described. Finally, the collaborative strategy of multi-technology integration and multi-disciplinary intersection is emphasized for the challenges faced in the identification, optimization, activity evaluation, and clinical application of NPs. It is hoped to provide a systematic overview and inspiration for exploring new drugs from natural resources in the future.
天然产物一直以来都是药物发现的重要来源，超过半数的获批药物都与天然产物有关，它们在复杂疾病的临床治疗中也展现出多方面的优势。然而，天然产物的生物活性筛选、靶点鉴定以及设计优化需要不断改进策略，药物作用机制的复杂性和技术策略的局限性给新药开发带来了诸多挑战。本文综述首先概述了基于生物活性和靶点的天然产物药物开发模式、天然产物筛选与衍生化的进展以及基因和蛋白质等主要靶点的优势与问题。接着，进一步讨论了基于靶点的药物以及鉴定和验证方法，以阐明其作用机制。随后，系统描述了传统技术和新兴技术在天然产物药物发现与开发中的应用现状及发展趋势。最后，针对天然产物的鉴定、优化、活性评估及临床应用中面临的挑战，强调了多技术整合与多学科交叉的协同策略。希望能为未来从自然资源中探索新药提供系统的概述和启发。
