催化酰胺类药物水解代谢酶的研究进展  

Research progress of hydrolases catalyzing amide drugs

作　　者：王誉晓 王新鸿 王丽梅 邱志霞[1] WANG Yuxiao;WANG Xinhong;WANG Limei;QIU Zhixia(School of Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学药学院,南京211198

出　　处：《中国药科大学学报》2025年第2期244-251,共8页Journal of China Pharmaceutical University

基　　金：国家自然科学基金项目(No.82274013)。

摘　　要：酰胺键是将分子中的氨基和羧基脱水缩合形成的分子键,其在药物结构设计中较为常见。酰胺键的稳定性受到多种因素的影响,使得酰胺类药物的药代动力学行为呈明显的代谢异质性。本文围绕酰胺类药物的药代动力学行为,提出水解酶在机体空间的表达和活性可能是引起酰胺类药物的药代动力学存在种属差异的重要原因之一,并归纳常见的水解酰胺类药物的酶或蛋白,为酰胺类药物的结构设计及临床研究提供参考;提出体外评价体系选择不当可能是导致药物药代动力学特征出现体内-体外不一致性的重要原因,总结目前用于评价药物体外代谢体系,为药物临床前评价提供参考。Amide bond is formed by dehydration and condensation of amino and carboxyl groups in a molecule,which is used in structural design of drugs.The stability of the amide bond is affected by many factors,which make the pharmacokinetic behaviors of amide drugs complicated by metabolic heterogeneity.This review proposes that the expression and activity of hydrolase may be one of the important reasons for the obvious differences in the pharmacokinetics of amides among species,summarizes the common metabolic enzymes or proteins responsible for hydrolyzing amides so as to provide some reference for the structural design and further clinical study of amide drugs,and suggests that improper selection of in vitro evaluation systems may be an important cause for the inconsistency between between in vitro and in vivo pharmacokinetic characteristics of drugs,with a summary of the currently used in vitro drug metabolism systems for drug evaluation,aiming to provide a basis for preclinical evaluation of drugs.

关 键 词：酰胺类药物 药代动力学 水解酶 

分 类 号：R969.1[医药卫生—药理学]