高通量分析药物代谢和毒性的研究进展

Research advance in high-throughput analysis on metabolism and toxicity of drugs

候选药物的不良反应往往是在新药研发的临床前或临床研究时才被发现,使得大量的候选药物在研究后期遭到淘汰,这不仅耗费大量的经费,而且大大降低了新药研发的产率。因此,目前非常需要发展能够在新药研发早期对候选药物的代谢和毒性进行有效预测的新技术,尤其是在最初的新药筛选和先导化合物优化阶段。虽然目前在新药研发的大部分阶段都已经出现高通量筛选技术,但是将这些技术转化成可以准确模拟候选药物在人体内的代谢以及预测候选药物或代谢物的毒性还是相当困难的。然而,近几年许多科学家在这方面也取得了一些令人鼓舞的最新成果,这些研究成果将有可能在新药研发中得到广泛的应用。

A large number of drug candidates fail at last stages of the drug discovery process,which is owing to poor drug candidate safety profiles identified in the preclinical and clinical phases,and it contributes to the high cost and low yield of drug discovery.As a result,new tools are needed to accelerate the assessment of drug candidate toxicity and human metabolism earlier in the drug development process,especially in primary drug candidate screening and lead compound optimization.Although high-throughput screens exist at many phases of the study of new drugs,it is difficult that transforming such screening techniques to platforms that can accurately simulate the metabolism of human in vivo and predict the toxicity of drug candidates or metabolin.Nevertheless,many scientists get some challengingly new achievement in this aspect in recent years,which may be gained extensive application in the study of new drugs.