应用计算机和体外模型对系列化合物透膜性质进行早期快速评价结果的比较分析  

Comparative assessment of PAMPA,Caco-2 cell and VolSurf software for prediction of drug permeation through bio-membranes

作　　者：庄笑梅[1] 刘萍霞[1] 张志伟[1] 张振清[1] 阮金秀[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国新药杂志》2008年第17期1486-1490,1511,共6页Chinese Journal of New Drugs

基　　金：国家“863”计划资助项目(2003AA2Z347B);北京市科学技术委员会基金资助项目(Z0004105040131)资助

摘　　要：目的:分别应用评价化合物透膜吸收性质的计算机及体外模型对系列化合物进行评筛,比较几种模型方法的相关性。方法:以军事医学科学院毒物药物研究所设计合成的晚期糖基化终产物(advancedglycosylation end products,AGEs)裂解剂系列化合物为研究对象,分别利用计算机、人工膜(the Parallel Arti-ficial Membrane Permeation Assay,PAMPA)及Caco-2 cell模型进行评价,并对3种模型的评价结果进行比较。结果:VolSurf软件模型库虚拟筛选结果与Caco-2细胞进行体外筛选结果的相关系数(r2)为0.549 2,VolSurf虚拟预测与PAMPA体外筛选相关性为0.753 1,PAMPA体外筛选结果与Caco-2细胞体外筛选结果的相关系数为0.685 7。结论:由于计算机及体外模型的方法各有优势及不足,在药物研发的不同阶段应用不同的模型进行筛选评价是完全必要且可行的。Objective：To compare the predictive abilities of drug permeation through bio-membranes with computational or in vitro models. Methods： Series compounds of advanced glyeosylation end products （AGEs） breakers designed and synthesized by our institute were taken as test set. The parallel artificial membrane permeation assay （PAMPA） , Caeo-2 cells and VolSurf software were used respectively. The emphasis was placed on the practical usefulness to pharmaceutical drug discovery. Results： The correlation coefficient between Caco-2 cell screening and in silico prediction was 0. 549 2, the correlation coefficient between PAMPA and in silico prediction was 0. 753 1, while the correlation coefficient between PAMPA and Caco-2 cell screening was 0. 685 7. Conclusion ： It has been demonstrated that the three approaches are valid and feasible in different stage of drug discovery.

关 键 词：CACO-2细胞 人工膜 VOLSURF 晚期糖基化终产物 

分 类 号：R914[医药卫生—药物化学]