摘要
目的:对新型吲哚胺2,3-双加氧酶1(IDO1)抑制剂氟哌色胺酮(TC-FPT)的体外和体内生物活性及药代动力学进行了初步研究,以期对该药物的开发提供参考。方法:通过体外IDO1酶抑制实验考察化合物的体外靶点活性;通过HEK-293细胞的抑制实验检测化合物在细胞水平的药理活性;进一步采用小鼠肠癌CT26.WT同种移植瘤模型评估化合物在整体动物的体内药效;研究经口给药的体内药代动力学,以获得半衰期和生物利用度等重要的药动学参数。结果与结论:TCFPT盐酸盐在体外具有一定的抑制活性,且对小鼠肠癌CT26.WT同种移植瘤有显著的抑制作用。小鼠经口给药具有较好的生物利用度。
Objective:To preliminarily study the in vitro and in vivo biological activities and pharmacokinetics of TCFPT,a novel indoleamine 2,3-dioxygenase 1(IDO1)inhibitor,and to provide a reference for drug development.Methods:The in vitro target activity of the compound was investigated by IDO1 enzyme inhibition test in vitro,its activity at the cell level was determined by the inhibition experiment of HEK-293 cells and the in vivo efficacy in the whole animal was evaluated by the mouse colon cancer CT26.WT homograft tumor model.The pharmacokinetics of oral administration in vivo was studied to obtain important pharmacokinetic parameters such as half-life and bioavailability.Results&Conclusion:The results showed that TC-FPT hydrochloride had a certain inhibitory activity in vitro,and moreover had a significant inhibitory effect on mouse colon cancer CT26.WT homograft tumor.It has good bioavailability when administered orally in mice.
作者
池王胄
CHI Wangzhou(Shanghai Tianci International Pharmaceuticals Co.,Ltd.,Shanghai 201315,China)
出处
《上海医药》
CAS
2023年第21期70-75,80,共7页
Shanghai Medical & Pharmaceutical Journal
