摘要
线粒体是细胞内能量和活性氧自由基(ROS)的主要来源,在病理条件下对细胞的存活与死亡具有十分重要的调控作用。线粒体是药物毒性作用的重要靶标。一些抗病毒药物、抗肿瘤药物和抗生素等可显著诱导肝脏和心脏等靶器官线粒体损伤。药物诱导的线粒体损伤可能涉及多条途径和多种机制。近年来研究表明,线粒体毒性可能是多种已上市药物被迫撤市或受到美国FDA"黑框"警告以及候选药物研发失败的重要原因。因此,在创新药物研发过程中,开展线粒体毒性评价具有十分重要的意义。
Mitochondria are the major sources of cellular energy and reactive oxygen species （ROS） , pla- ying fundamental roles in regulation of cell survival and death under pathological conditions. Mitochondria are im- portant targets of drug toxicity. A variety of drugs, eg. antivirals, anti-cancer drugs, and antibiotics, have been shown to significantly induce mitochondrial toxicity in targeted organs such as liver and heart. Drug-induced mito- chondrial injury may involve multiple pathways and mechanisms. Recently, it has been suggested that mitochondri- al toxicity is the main cause leading to the failure of drug development, and many post-market drugs that have been withdrawn or received Black Box warnings from the FDA are characterized by mitochondrial toxicity. Thus, assess- ment of mitochondrial toxicity is of great significance in the research and development of innovative drugs.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2012年第16期1867-1871,共5页
Chinese Journal of New Drugs
基金
国家重大新药创制科技重大专项(2009ZX09501-034)
国家自然科学基金资助项目(81072711)
关键词
线粒体
毒性靶标
创新药物
安全性评价
mitochondria
targeted toxicity
innovative drug
safety evaluation
