手动膜片钳检测HMS-01对HEK293细胞hERG通道电流的影响

The effect of HMS-01 on stably expressed hERG channel currents in HEK293 cells detected with the manualpatch clamp method

目的检测新化合物HMS-01有无心脏毒性,对其进行临床前安全评价研究,为进入临床试验做准备。方法用手动膜片钳检测转染后hERG钾通道稳定表达的HEK293细胞的电流,西沙必利做阳性药,将HMS-01依次稀释成0.3、1、3、10、30μmol/L,依次作用于细胞,记录电流变化,计算抑制率。结果HMS-01在实验设计的最高浓度30μmol/L时,对细胞hERG钾通道的抑制率低于30%,与阳性对照药西沙必利相比,无明显抑制作用。结论新化合物HMS-01对hERG通道无明显抑制作用,不具有心脏毒性。

Objective To test the cardiac toxicity of new compound HMS-01 and evaluate the safety profile for clinical trials.Methods Manualpatch clamp method was used to measure human Ether-a-go-go-Related Gene(hERG)potassium channel currents with different concentrations of HMS-01.Cisapride was selected as the positive control drug.HMS-01 was diluted to the concentration of 0.3,1,3,10 and 30μmol/L and applied to the cells.The changes in electrical currents were recorded and the inhibition rate was calculated.Results At the highest concentration of 30μmol/L,the inhibitory rate of HMS-01 on hERG channel was less than 30%.There was no obvious inhibitory effect compared with cisapride.Conclusion Compared with the cisapride,HMS-01 has no obvious inhibitory effect on hERG channel and has no cardiotoxicity.