“精准医疗”背景下的分子靶向药物研究——精准药物设计策略浅析  

Contemporary Molecular Targeted Drug in the Context of “Precision Medicine”:An Attempting Discussion of “Precision Drug Design”

作　　者：展鹏[1] 王学顺[1] 刘新泳[1] 

机构地区：[1]山东大学药学院药物化学研究所化学生物学教育部重点实验室,济南250012

出　　处：《化学进展》2016年第9期1363-1386,共24页Progress in Chemistry

基　　金：国家自然科学基金重点国际合作研究项目(No.81420108027);国家自然科学基金面上项目(No.81573347;81273354);山东大学青年学者未来计划(No.2016WLJH32);山东省重点研发计划(重大关键技术)(No.2015ZDJS04001);山东省科技发展计划项目(No.2014GSF118012)资助~~

摘　　要：如何实现对肿瘤、病毒感染等严重危害人类健康的疾病的精准治疗是当前医学界的难题和研究热点。随着"精准医疗"计划的启动,当代药物设计也随之进入"精准"靶向药物分子设计时代。基于靶标结构的合理药物设计及特异性的药物递送系统是当代精准药物设计的重要方面。靶标-配体精准相互作用为基于靶标的合理药物设计奠定了理论基础;精准"制导"化学合成方法学的研究为药物合成提供了强有力的工具;灵敏、准确分子探针的研究为当代化学生物学及发现特异性的药物递送系统提供有效的辅助手段。本文从以上几方面,从药物化学的视角综述了"精准医疗"背景下的分子靶向诊疗药物研究。How to cure serious diseases w hich do harm to the health of human being such as tumor and virus infection by ＂precision medicine＂is alw ays a difficult problem and a research hotspot in the medical field. With the launch of ＂precision medicine ＂ project,contemporary drug design has reached the new era,namely,＂precise＂targeted drug molecular design should be one of the key pillars of precision medicine. The structurebased rational drug design and the targeted drug delivery system are important aspects of the contemporary＂precision drug design＂. Precise noncovalent interactions between ligands and proteins lay the theoretical foundations for structure-based rational drug design. The development of new synthetic methodologies provides a pow erful tool for drug precise synthesis,focusing both on the identification of intrinsically novel reactions,as w ell as the discovery of improved methods for carrying out existing transformations. Chemical biology has a significant role to play in the discovery and validation of new therapeutic targets. Over the past few years,manysensitive and accurate probes based on small organic molecules have demonstrated considerable promise in＂precision drug design＂as they provide a chemoproteomic means to confirm and quantify target engagement and selectivity of small molecule drug candidates. In the view point of medicinal chemistry,this review highlights recent advances made in contemporary molecular targeted drug design in the context of ＂precision medicine＂.

关 键 词：精准医疗 分子靶向药物 精准药物设计 药物化学 探针 化学生物学 药物发现 

分 类 号：R914.2[医药卫生—药物化学] O621.3[医药卫生—药学]