表型药物筛选技术助力基于中药的创新药物发现

Phenotypic drug discovery promotes research and development of innovative drugs based on traditional Chinese medicine

我国中草药资源丰富,对复杂疾病具有良好的治疗作用,具有巨大的开发潜力。但其成分复杂,药效物质及其作用机制不明,且缺乏科学的临床安全性和有效性的评价方法,极大地限制了基于中药的创新药物研发。随着人工智能、仿生生物学等前沿学科的发展,特别是细胞画像、器官芯片等技术和产品的涌现,有望实现基于模型宏、微观性状或特征变化的中药及其组分功效的高通量鉴别,为中药的研发和应用提供更加精准的指导。因此,作为全新药物发现的主要手段之一,表型药物筛选在基于中药的创新药物研发过程中越来越受到关注。近年来,表型药物筛选技术不断发展更新,显著提升了新药早期发现率及后期研发成功率,逐渐成为全新药物研究的重要工具。该文通过探讨中药创新药物发现的潜力及挑战,结合表型药物筛选在新药发现中的优势,详细阐述了在细胞画像、深度学习和器官芯片等前沿技术的支持下,表型药物筛选技术的应用如何推动传统中医药进入新的发展阶段。

Traditional Chinese medicine with rich resources in China and definite therapeutic effects on complex diseases demonstrates great development potential.However,the complex composition,the unclear pharmacodynamic substances and mechanisms of action,and the lack of reasonable methods for evaluating clinical safety and efficacy have limited the research and development of innovative drugs based on traditional Chinese medicine.The progress in cutting-edge disciplines such as artificial intelligence and biomimetics,especially the emergence of cell painting and organ-on-a-chip,helps to identify and characterize the active ingredients in traditional Chinese medicine based on the changes in model characteristics,thus providing more accurate guidance for the development and application of traditional Chinese medicine.The application of phenotypic drug discovery in the research and development of innovative drugs based on traditional Chinese medicine is gaining increasing attention.In recent years,the technology for phenotypic drug discovery keeps advancing,which improves the early discovery rate of new drugs and the success rate of drug research and development.Accordingly,phenotypic drug discovery gradually becomes a key tool for the research on new drugs.This paper discusses the enormous potential of traditional Chinese medicine in the discovery and development of innovative drugs and illustrates how the application of phenotypic drug discovery,supported by cutting-edge technologies such as cell painting,deep learning,and organ-on-a-chip,propels traditional Chinese medicine into a new stage of development.