先导化合物结构优化策略(八)——药物转运体及其相关药物设计策略  

Lead compound optimization strategy(8)-drug transporters and related drug design strategies

作　　者：宋晓翰 王江 柳红 SONG Xiao-han;WANG Jiang;LIU Hong(State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]中国科学院上海药物研究所,新药研究国家重点实验室,上海201203 [2]中国科学院大学,北京100049

出　　处：《药学学报》2021年第2期432-444,共13页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(21632008).

摘　　要：转运体会对药物在人体中的转移和分布产生极大的影响。一方面可溶性载体转运体可以将药物转运进入组织器官,从而提升药物生物利用度以及改变药物的组织分布;另一方面,细胞上的ATP结合盒转运体会将某些药物排出细胞,从而降低细胞内药物浓度,产生耐药性。本文总结了人体中几种重要的药物转运体的底物特征以及针对药物转运体进行药物设计的策略,包括前药修饰提高生物利用度、引入酸性基团改善肝脏选择性、改善化合物极性降低外排比等。Transporters have a great influence on the transportation and distribution of drugs in the body.On the one hand,solute carrier transporters could transport drugs into tissues and organs,which may improve the oral bioavailability or change the tissue-distribution of the drugs.On the other hand,the ATP-binding cassette could pump some drugs out of the cell,which decreases the intracellular drug concentrations and leads to drug resistance.This paper summarizes the distribution,substrate characteristics and drug design strategies of several important drug transporters,such as improving bioavailability by prodrug design,introducing acid group to improve hepatic selectivity and adjusting the polarity of compounds to decrease efflux ratio.

关 键 词：转运体 药物设计 先导化合物 

分 类 号：R916[医药卫生—药学]