毒性是導(dǎo)致藥物研發(fā)失敗的主要原因之一。為了避免在藥物開發(fā)晚期發(fā)現(xiàn)毒性導(dǎo)致的昂貴代價，盡早確定藥物潛在的毒性問題非常重要。通過對藥物產(chǎn)生的肝臟、心臟和腎臟毒性的機制進行分析，并對現(xiàn)有的毒性預(yù)測方法進行綜述，提出可以從代謝產(chǎn)物反應(yīng)活性、離子轉(zhuǎn)運體、離子通道等3方面綜合分析藥物產(chǎn)生毒性的可能性，從而提高重要臟器嚴重毒性預(yù)測的準確性。

Toxicity is one of the major reasons causing a drug failure. Therefore, in order to advoid and reduce the high price of drug failures due to the toxicity in late development, it is essential to determine potential toxicity problems as early as possible. In this paper the mechanism of drug-caused toxicity in various injured organs, such as liver, heart, and kedney, was analyzed and summarized and computational methods corresponding to different toxicity mechanisms have been listed to predict toxicity of drugs. These computational methods could be feasible in the comprehensive analysis on reactivity of metabolite, ion transporter, and ion channel, and may be useful in improving the accuracy of toxicity prediction.

基金項目：國家重大新藥創(chuàng)制專項（2008ZX09305-005與2011ZX09401-009）