重组人代谢酶酵母表达系统在新药体外代谢研究中的作用

Application of recombinant human metabolic enzyme yeast system in metabolic research of new drug in vitro

重组人代谢酶酵母表达系统是指利用基因重组技术将人的药物Ⅰ相代谢酶和Ⅱ相代谢酶基因转染至酵母细胞从而高效地获得单一的重组人代谢酶酵母。本文通过查询国内外文献总结了重组人代谢酶酵母表达系统在新药体外代谢研究中的作用。在新药研发的早期阶段,利用重组人代谢酶酵母系统,确定候选药物(或新药)的代谢途径及代谢酶亚型;评估候选药物(或新药)对代谢酶的诱导和抑制作用;研究代谢酶基因多态性相关的药物相互作用;筛选和制备候选药物(或新药)的新代谢物。重组人代谢酶酵母表达系统不仅为新药研发提供更加高效、便利的高通量新药筛选平台,也为候选药物的安全性评价提供物质基础。

Recombinant human metabolic enzyme yeast systems are developed by introducing genes of human enzymes involved in phase I and II drug metabolism into yeast,which are used to efficiently produce single type of human metabolic enzyme. The yeast systems are broadly used in in vitro metabolism studies in new drug development. In the early stage of new drug development,recombinant human metabolic enzyme yeast systems are mainly used to： 1） verify the metabolic pathways and metabolic enzyme subtypes of candidate drugs（ or new drugs）,2） evaluate candidate drugs（ or new drugs） inducing or inhibiting the metabolic enzymes,3） investigate the drug interactions of the enzyme gene polymorphism,and 4） screen and prepare new metabolites of candidate drugs（ or new drugs）. Recombinant human metabolic enzyme yeast systems have not only provided more efficient and convenient high-throughput drug screening method for new drug development,but also laid the foundation for the safety evaluation of candidate drugs.