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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。
Summarize PAC-1 antitumor activity, mechanism of action, toxicity, structure modification and drug substitution and other research results, provide a reference for the study of the mechanism of antitumor agent PAC-1. The literature of PAC-1, which is related to anticancer drug PAC-1, is reviewed in this paper. The analogues of PAC-1, pharmacodynamics in vitro and in vivo, anticancer mechanism, toxicology and pharmacokinetics are summarized. The results showed that PAC-1 can selectively inhibit the activity of tumor cells in vitro and induce apoptosis by directly activating procaspase-3. In vivo, the antitumor effect of PAC-1 was clear. For the NCI-H226 subcutaneous transplantation model of lung cancer, intragastric administration The inhibition rate of 50 mg.kg-1 reached 53% and the inhibition rate of 100 mg.kg-1 reached 77%. PAC-1 has strong antitumor activity both in vivo and in vitro, but also has the shortcomings of low bioavailability and neurotoxicity. It can be further modified by structural modification to further improve the activity and bioavailability and reduce the possible toxicity, so that the next generation The design and discovery of procaspase-3 activator provides a very important guideline and reference value.