基于毒性通路扰动的药物安全性评价新策略

Toxicity pathway perturbation-based new strategy of drug safety evaluation

安全性是决定创新药物研发成败的关键因素。传统的药物毒性测试与安全性预测面临严峻挑战。基于毒性通路扰动的毒性测试策略已成为药物安全性评价的重要发展方向。本文针对传统毒性测试方法存在的问题,简要介绍了毒性通路的内涵及其毒理学意义,重点阐述了基于毒性通路扰动的安全性评价新策略的提出及其发展,并以药物线粒体毒性预测为例,介绍了毒性测试新策略的原理及应用,为药物安全性评价的发展提供新的思路。

Safety is crucial to the success of of innovative drug research and development.Traditional drug toxicity testing and safety prediction are faced with severe challenges. Toxicity pathway purterbation-based toxicity testing strategies have become an important direction for drug safety evaluation. To address the problems with traditional toxicity testing, this review introduces the definition and toxicological significance of toxicity pathway, focused on illustration of the proposal and development of a new strategy of safety evaluation based on toxicity pathway perturbation, and describes the principle and application of this new strategy by taking mitochondrial toxicity prediction as a case study in order to provide a new paradigm for the development of drug safety evaluation.