抗肿瘤药PAC-1研究进展  

Advance of Antitumor Candidate:PAC-1

作　　者：龚曼[1,2,3] 游云[1,3] 常青[1,3,4] 刘晓谦[1,3] 王智民[1,3] 

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]河南中医学院,郑州450008 [3]中药质量控制技术国家工程实验室,北京100700 [4]陕西中医学院,咸阳712046

出　　处：《中国实验方剂学杂志》2013年第15期348-353,共6页Chinese Journal of Experimental Traditional Medical Formulae

摘　　要：归纳总结PAC-1抗肿瘤活性、作用机制、毒性、结构修饰及药代等研究成果,为抗肿瘤药PAC-1作用机制的研究提供参考。现查阅近年来相关抗肿瘤药PAC-1的文献,针对PAC-1的类似物、体内和体外药效学、抗癌机制、毒理学及药动学等进行综述。结果显示体外研究PAC-1能够选择性地抑制肿瘤细胞活性,通过直接激活procaspase-3诱导细胞凋亡;体内研究PAC-1抗肿瘤作用明确,对肺癌NCI-H226皮下移植模型,灌胃给药50 mg.kg-1抑瘤率达到53%,100 mg.kg-1抑瘤率达到77%。PAC-1在体内和体外均具有较强的抑瘤活性,但也存在生物利用度低和神经毒性的缺点,可以通过结构改造以进一步提高活性与生物利用度,降低可能的毒性,为下一代procaspase-3活化物的设计和发现提供十分重要的指导意义和借鉴价值。PAC-1 is a new type of small molecular targeted drugs which is being developed for caspase-3 zymogen（procaspase-3） in recent years.Studies in vitro have shown that it can selectively inhibit tumor cell activity,by directly activating procaspase-3 to induce apoptosis.Its anti-tumor effect is clear in vivo.For the NCIH226 subcutaneous transplanted mice model of lung cancer,the inhibition rate of 50 mg.kg-1 reached 53%,and inhibition rate of 100 mg.kg-1 reached 77% by intragastric administration.In this review we also discussed its analogues,pharmacodinanics,mechanism,toxicology and pharmcokinetics.These results demonstrate that PAC-1 has reliable antitumor activities in vivo and in vitro,but PAC-1 also have disadvantages of low bioavailability and neurotoxicity.In the future,its chemical structure can be modified to improve anti-tumor activities,bioavailability,and reduce the possible side-effects or toxicities.

关 键 词：PAC-1 类似物 药效学 机制 毒理学 药动学 

分 类 号：R285.5[医药卫生—中药学] R284.1[医药卫生—中医学]