新型酪氨酸激酶抑制剂对hERG钾通道电流作用研究  

Effectiveness of new tyrosinase inhibitors against hERG potassium channel currents

作　　者：王宁波[1] 汪溪洁[1] 马璟[1] 

机构地区：[1]中国医药工业研究总院,上海医药工业研究院,国家上海新药安全评价研究中心

出　　处：《世界临床药物》2012年第4期211-214,共4页World Clinical Drug

基　　金："重大新药创制"科技重大专项(编号:2008ZX09305);上海市科委科研计划项目(编号:09DZ2290900)资助

摘　　要：目的探讨新型酪氨酸激酶抑制剂对hERG钾通道电流的影响。方法应用全细胞膜片钳技术,记录HEK293细胞异源表达的hERG钾电流,观察新型酪氨酸激酶抑制剂对hERG钾通道电流的抑制作用。结果新型酪氨酸激酶抑制剂能作用于hERG钾通道,并以浓度依赖的方式抑制hERG钾电流,半数抑制浓度(IC50)分别为PA1101(10.80±3.01)μmol/L,PA1102(9.55±1.81)μmol/L,PA1103(1.69±0.26)μmol/L,PA1104(1.17±0.49)μmol/L,PA1105(0.08±0.02)μmol/L,PA1106(0.001 9±0.000 7)μmol/L。结论新型酪氨酸激酶抑制剂对hERG钾通道有较强烈的阻断作用,建议结合临床使用剂量与血药浓度进行安全性评估。Objective To investigate the effects of tyrosinase inhibitors against the hERG potassium channel currents. Methods The whole cell patch clamp technique was selected to record hERG potassium channel currents form HEK293 cells heterologous expressed with hERG gene. Results The new tyrosinase inhibitors inhibited hERG potassium channel currents in a concentration-dependent manner, with 1C5o of PAll01 10.80±3.01μmol/L, PA1102 9.55±1.81μmol/L, PAll03 1.69±0.26 μmol/L, PAll04 1.17±0.49μmol/L, PAll05 0.08±0.02μmol/L, PAll06 0.001 9±0.000 7 μmol/L. Conclusion New tyrosinase inhibitors can block the hERG potassium channel. Its IC5o should association with the clinical dose and drug concentration in blood to do the safety assessment.

关 键 词：HERG钾通道 长Q—T间期综合征 电生理学 酪氨酸激酶抑制剂 

分 类 号：R979.1[医药卫生—药品]