论文部分内容阅读
遗传毒性评价是药物临床前安全性评价研究的重要环节,目前ICH推荐的的标准试验组合基本能够满足新化学实体注册遗传毒理学实验数据的需求。然而随着全程式毒理学研究模式的推进,各制药公司越来越重视在创新药物研发早期进行遗传毒性初筛,及早发现具有潜在遗传毒性的候选化合物,降低新药开发的风险。作为在新药研发早期用于遗传毒性初筛的试验方法,除了要求灵敏、快速、经济外,还必须尽量减少化合物的用量,逐步实现高通量和自动化的要求。文中综述了目前研究比较广泛的早期体外遗传毒性初筛试验方法的原理、检测终点和应用进展,为候选化合物的早期遗传毒性初筛工作的深入开展提供技术指导。
Genotoxicity assessment is an important part of preclinical safety evaluation of drugs. Currently, the standard combination of tests recommended by ICH basically meets the requirements of the new chemical entities for registration of genotoxicity experimental data. However, with the advent of a full-fledged toxicology research paradigm, pharmaceutical companies are increasingly focusing their efforts on early genotoxicity screening in the early stages of innovative drug discovery and early detection of potentially genotoxic candidate compounds, reducing the risk of new drug development. As a test method for the preliminary screening of genotoxicity in the early stage of new drug research and development, in addition to being sensitive, rapid and economical, it is also necessary to minimize the dosage of the compound and gradually realize the requirements of high throughput and automation. This review summarizes the principles, testing endpoints and application progress of early genotoxicity primary screening tests currently widely studied, and provides technical guidance for the further screening of early genotoxicity of candidate compounds.