文献类型：期刊文献

中文题名：药物潜在靶标识别与药物设计方法研究

英文题名：Method development for potential drug target identification and drug discovery

作者：龚道鸿[1];唐建新[1];王保利[2];相苏桐[1];冯紫燕[2];李诗良[1];李洪林[1,2]

机构：[1]华东师范大学药学院,人工智能新药创智中心,上海200062;[2]华东理工大学药学院,上海200036

年份：2025

卷号：55

期号：8

起止页码：2223

中文期刊名：中国科学:化学

外文期刊名：SCIENTIA SINICA Chimica

收录：;北大核心:【北大核心2023】；

基金：国家重点研发计划(编号:2022YFC3400501);国家自然科学基金(编号:82425104)资助项目。

语种：中文

中文关键词：靶标识别;药物设计;人工智能;计算方法与平台;新药研发

外文关键词：target identification;drug design;artificial intelligence;computational methods and platforms;new drug development

摘要：药物靶标识别与验证是新药研发的首要环节,其关键挑战在于筛选出同时满足疾病机制关联性、结构可靶向性及成药潜力的生物分子靶标.通过早期且全面的靶标验证,可明确建立靶点调控与疾病治疗效应的因果关系.基于对靶标三维结构及功能特征的深度解析,结合理性药物设计策略,能够高效发现和优化与靶标特异性结合的活性化合物,显著缩短药物发现周期并降低研发成本.在复杂疾病治疗领域,靶标发现技术与药物设计方法的协同应用,不仅提升了药物的靶向性和治疗效力,更推动了医药研发范式从“广谱治疗”向“精准干预”的转型.本文系统总结本课题组近二十年在靶标识别、药物设计以及人工智能药学等方法和平台上的发展及原创新药研究进展,并基于当前研究态势,深入探讨药物设计领域亟待解决的关键科学问题,进而对未来发展趋势与挑战提出展望.
Drug target identification and validation constitute the fundamental stage in novel drug development.The principal challenge lies in identifying biomolecular targets that concurrently fulfill three critical requirements:relevance to disease mechanisms,structural targetability,and therapeutic potential.Through systematic and comprehensive target validation,researchers can establish definitive causal relationships between target modulation and therapeutic outcomes.By conducting thorough analyses of target three-dimensional structures and functional characteristics,integrated with rational drug design approaches,scientists can effectively discover and optimize target-specific bioactive compounds.This strategy substantially reduces both the drug discovery timeline and associated research and development expenditures.In complex disease therapeutics,the combined implementation of target discovery technologies and drug design methodologies has yielded dual benefits:enhanced drug targeting capability and treatment efficacy,while simultaneously driving the evolution of pharmaceutical research and development from conventional broad-spectrum therapies toward precision medicine interventions.This review comprehensively outlines our research group’s methodological and technological advancements over two decades in multiple areas,including target identification,drug design,and AI-assisted pharmacology,along with corresponding progress in pioneering drug development.Furthermore,based on contemporary research landscapes,we examine pressing scientific challenges in drug design and provide insightful projections regarding future developments and potential obstacles in the field.