Cardiac Safety Services

ChanPharm’s Cardiac Safety Services

Continuous cardiac toxicity testing is essential for successful drug discovery and development. ChanPharm’s cardiac safety studies are based on detailed electrophysiological studies of drug effects on cardiac ionic channels expressed in mammalian cell lines, assessment of drug effects on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and in-silico reconstruction of drug effects of human ventricular action potentials.

ChanPharm provides the following high quality cardiac safety assays using human iPSC-derived cardiomyocyte cells:

  • Safety Services on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)
  • Multi Electrode Array (MEA; Multi Channel Systems platform) technology
  • Cardiac safety studies on mammalian cell lines with automated patch clamp platforms
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Safety Services on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)

  • Multi Electrode Array (MEA; Multi Channel Systems platform) technology
  • Action potential measurements with the voltage-sensing optical technique
  • Action potential measurements on hiPSC-CMs with manual patch clamp

Multi Electrode Array (MEA) technology

Field potential recordings with MEAs on hiPSC-CMs measure spike amplitude, field potential duration and the beat period. The AMP provides an indirect measure of drug effects on the action potential upstroke. Effects on repolarization are estimated from changes in the field potential duration, corresponding to the QT interval of the clinical electrocardiogram.

Cardiac safety studies with automated patch clamp platforms

ChanPharm’s cardiac safety services take into account the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. Patch clamp studies are performed on a large panel of human cardiac ion channels, including the six CiPA ion channels (Kv11.1 (hERG), Cav1.2, Nav1.5, Kv7.1 (minK), Kv1.5, Kir2.1, Kv4.3/Chip2, Cav3.2, others upon request).
We perform:

  • Cardiac safety studies with manual patch clamp
  • In-silico simulations of pro-arrhythmic drug effects on cardiac action potentials that account for multi-ion channel block
  • Analysis of torsadogenic probabilities of compounds based on logistic regression models
Cardiac Safety Service

ChanPharam’s technology platforms for cardiac safety studies

  • Multi electrode arrays (MEAs) for field potential recordings of human iPSC-derived cardiomyocytes provide information on potential effects on the Q-T interval
  • Voltage-sensing optical techniques (imaging) provide information on upstroke velocity and repolarisation parameters of the cardiac action potential
  • Action potential recordings on human iPSC-derived cardiomyocytes with manual patch clamp provide information on upstroke velocity and repolarisation parameters of the cardiac action potential and the resting membrane potential
  • Action potentials from human iPSC-derived cardiomyocytes with automated patch clamp provide information on upstroke velocity and repolarisation parameters of the cardiac action potential
  • Contractility studies on human iPSC-derived cardiomyocytes
  • In-silico studies to determine the potential torsadogenic risk of multi-channel blockers

Available technologies

  • Synchropatch (384 cell format, Nanion technology)
  • Patchliner (16 cell format, Nanion technology)
  • Multi electrode arrays (MEAs, Multi Channel Systems, Reutlingen)
  • Fluorescence microscopy with a high-speed sCMOS camera (Kinetix, Photometrix)
  • Manual patch clamp studies for whole-cell measurements of action potentials under gigasel conditions
  • Fluorescence microscopy for action potentials and calcium measurements on iPSC-derived cardiomyocytes
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