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    Comprehensive in vitro Proarrhythmic Assay (CiPA)

    CiPA Panel The Comprehensive in vitro Proarrhythmic Assay (CiPA) is a series of assays designed to predict arrhythmias and not simply QT prolongation.

    1. Detailed information

    QT prolongation is a serious and widespread adverse drug reaction. One-third of drugs withdrawn from the market due to the adverse drug-induced arrhythmias. Drug-induced delayed ventricular repolarization in some cases may trigger a fatal arrhythmias-torsional apical ventricular tachycardia.

    The hERG assay is currently considered a model of choice for evaluation of cardiac pro-arrhythmic risk. The safety guidelines issued by IchS7B, in 2005, mentioned all the drugs at the filing stage must have hERG evaluation assay data. As, is the technical guidelines for the extension of the drug QT interphase non-clinical research (2014) of the drug QT.

    The sensitivity and specificity of the hERG Assay was a serious problem, therefore, in 2013 FDA starts promoting wide-range in vitro arrhythmia evaluation assay (CiPA, Comprehensive in vitro Proarrhythmia Assay). The CiPA pathway consists of four main elements, 1) assessment of drug effects on the critical human ventricular ion channel currents, 2) in silico integration of the ion channel effects to determine the net effects on the cardiac action potential, and 3) a check for discrepancies in fully integrated biological systems (stem-cell-derived cardiac myocytes and the human ECG) 4) clinical electrocardiogram evaluation.


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    ICE Bioscience offer different cardiac evaluatioN services. 


    ICE Bioscience Cardiac Ion Channel Panel


    Targets

    Function

    Positive Control

    Method*

    hERG(GLP

    available)

    IKr, rapid repolarization (phase 3)

    cisapride

    MPC, APC

    Nav1.5

    INa, depolarization (phase 0)

    TTX, flecainide

    MPC, APC

    Cav1.2

    ICa-L, depolarization (phase 2)

    nifedipine

    MPC, APC

    Kv7.1/minK

    IKs/KvLQT, slow repolarization (phase 3)

    Chromanol 293B

    MPC, APC

    Kv1.5

    IKur, repolarization (atrial)

    4-AP

    MPC, APC

    Kv4.3

    Ito, repolarization (phase 1)

    4-AP

    MPC, APC

    Kir2.1

    IK1, repolarization (phase 4)

    BaCl2

    MPC, APC

    Kir3.1/3.4

    KAch, repolarization (atrial)

    BaCl2

    MPC

    Kir6.2/SUR2

    KATP

    glibenclamide

    MPC

    Cav3.2

    ICa-T, pacemaker current

    NiCl2

    MPC, APC

    HCN2

    If, pacemaker current

    ivabradine

    MPC

    HCN4

    If, pacemaker current

    ivabradine

    MPC

    *MPC= Manual patch clamp, APC= Automated patch clamp (Nanion Patchliner ® /Qpatch HTX48)


    1. Research on multple cardiac ion channels


    ICE cardiac panel

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    ICE cardia panel (CiPA protocol)

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    IPSC derived cardiomyocytes AP


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