基于片段方法创制的药物  

FBDD and drugs originated from FBDD

作　　者：郭宗儒[1] GUO Zong-ru(Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2023年第12期3490-3507,共18页Acta Pharmaceutica Sinica

摘　　要：小分子药物与靶标的结合大都以非共价键结合,氢键、静电、疏水和范德华作用以维持结合力,这些因素越多结合越牢固,活性越强。但往往伴随分子尺寸变大,产生过膜吸收代谢等药代问题,最终影响成药性。基于片段的药物发现(fragment-based drug discovery,FBDD)是普筛高质量片段以发现苗头分子,结合结构生物学,在片段生长、连接和融合中形成先导物,以及优化出候选物的运行中,始终兼顾化合物活性和物化性质之间的协调性。基于片段的药物发现与基于靶标结构的药物发现存在密切关系。本文以数个上市的药物简释FBDD的应用原理。The binding of small molecule drugs to targets is mostly through non-covalent bonds,and hydrogen bond,electrostatic,hydrophobic and van der Waals interactions function to maintain the binding force.The more these binding factors lead to strong bindings and high activities.However,it is often accompanied by the increase of molecular size,resulting in pharmacokinetic problems such as membrane penetration and absorption,as well as metabolism,which ultimately affects the drug success.Fragment-based drug discovery(FBDD)is to screen high-quality fragment library to find hits.Combine with structural biology,FBDD generates lead compounds by means of fragment growth,linking and fusion,and finally drug candidates by the optimization operation.During the value chain FBDD is closely related to structure-based drug discovery(SBDD).In this paper,the principle of FBDD is briefly described by several launched drugs.

关 键 词：基于片段的药物发现 计算机辅助药物设计 配体效率 片段生长、连接和融合 

分 类 号：R914[医药卫生—药物化学]