CiPA Phase II non-core site studies : iCell cardiomyocyte<sup>2</sup>における細胞外電位とインピーダンスシグナルに対する12化合物の作用

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  • 加藤 英里子
    東京大学大学院薬学系研究科化学物質安全性評価システム構築社会連携講座
  • 馬場 敦
    東京大・院薬・薬品作用
  • 池谷 裕二
    東京大学大学院薬学系研究科化学物質安全性評価システム構築社会連携講座 東京大・院薬・薬品作用 東京大学大学院薬学系研究科ヒト細胞創薬学寄附講座
  • 澤田 光平
    東京大学大学院薬学系研究科化学物質安全性評価システム構築社会連携講座 東京大学大学院薬学系研究科ヒト細胞創薬学寄附講座

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  • Effects of 12 compounds on field potential signals with xCELLigence CardioECR system using iCell cardiomyocyte<sup>2</sup>

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<p>Human iPSC cardiomyocytes (hiPS-CMs) have been used for the risk assessment of drug-induced QT prolongation and ventricular tachycardia called torsade de pointes. We have evaluated 12 compounds using CardioECR. The 12 compounds include high (azimilide, bepridil, dofetilide, ibutilide), intermediate (chlorpromazine, cisapride, clarithromycin, clozapine) and low (diltiazem, loratidine, metoprolol, mexiletine) risk classes. The effects of these compounds on field potential (FP) and impedance signals were evaluated with iCell cardiomycytes2. In the high risk group, azimilide, dofetilide and ibutilide prolonged the field potential duration (FPD) and induced EADs, but bepridil stopped the beating at the highest concentration. In low risk group compounds, diltiazem, metoprolol and mexiletine stopped beating, and loratidine showed no apparent change in FPD. The intermediate compounds stopped beating or induced EADs at higher concentrations. These results suggested that CardioECR can be used as a platform to assess the QT risk with hiPS-CMs. As CardioECR can utilize the impedance data in addition to the FP signals, an integrated analysis using both signals is useful for more accurate interpretation of compound nature.</p>

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