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QTempo

QTempo

Assay service of cardiotoxicity and comprehensive analysis of cardiac ion channels using human iPS cell derived beating cardiomyocyte

Cat.No.: RCESD005

Lead time: Two weeks

Cardiac ion channels function in a sequential and interactive manner to drive the beating of cardiomyocytes. QTempo is the only human pre-clinical functional assay that can capture the complexity of that process. The underlying idea is simple: We (1) generate clusters of spontaneously beating cardiomyocytes from human iPS cells, (2) place these beating cardiomyocytes in a well with electrodes to monitor electropotential, and (3) Measure the effect of compounds and drugs on the waveform.

From this simple idea, the QTempo assay allows analysis of the full range of ion channels. QTempo directly measures not only QT interval, but also a range of other cardiac action potential parameters (such as beat rate and the QRS complex). QTempo identifies compounds that affect Na, K and Ca ion channels and reflects their complex interactions.

The cardiomyocyte clusters used in QTempo generate robust, consistent data over extended periods. This allows a wide variety of drug concentrations to be sequentially tested, increasing confidence in drug safety before further development.

ReproCELL’s QTempo assay is offered in a variety of formats to suit customer requirements. ReproCELL is licensed by iPS Academia (Kyoto, Japan) to use iPS technology in this assay.

In all our tests, including assays of cardiotoxic compounds not correctly identified by the hERG assay, QTempo has generated results in complete agreement with clinical findings.

Two key technologies developed by ReproCELL underlie QTempo. The first is a protocol for the differentiation of cardiomyocytes from both ES and iPS cells. Secondly, ReproCELL has developed novel protein-free media that maintain the cardiomyocytes whilst allowing stable measurement of electropotential.

    *  Uses beating human heart cells
    *  Identifies beat rate dependent effects
    *  Identifies compounds that change beat rate
    *  Covers all cardiomyocyte ion channels
    *  Screens non-ion channel factors
    *  Faster, cheaper and kinder than using animals

ReproCELL offers QTempo as a service to the drug development industry and to other industries interested in cardiac safety profiling.

For more information on how QTempo can help you Beat Cardiotoxicity, complete the contact form and mention QTempo

or send an e-mail with your contact details

info_repro@reprocell.com



 

 


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Dose dependent QT interval prolongation (y axis) caused by increasing concentrations (x axis) of a variety of reference compounds. Aspirin, Astemizole, E-4031, di-sotalol, verapamil, rofecoxib, cisapride


 

 

 

Dose dependent QT prolongation caused by various Na and P specific ion channel blockers. TTX Na blocker, Nimodipine Ca-L blocker, Mibefradil Ca-T blocker, Nifekalant Ikr-blocker, Terfenadine Ikr/Ikur blocker, Methoctramine M2 ant/Ach blocker

 

 

 

 

 

Effects on the QRS complex caused by an L type Ca blocker (Nimodipine)

 


 

 

Non-ion channel mediated effects: QT interval prolongation caused by specific binding of acetlycholine to the M2 muscarinic acid receptor. In this figure, waevforms generated at ascending doses of acetylcholine are overlaid.

 

 

 

 

 

Brachycardia caused by acetylcholine. Increasing concentrations of acetycholine (towards bottom of figure) reduce beat rate seen here as an increase in the interspike interval