Beyond hERG for cardiac liability testing
Gain a broader insight into potential cardiac risk with earlier profiling of new chemical entities at throughputs that are more appropriate for lead discovery and optimization. CardiacProfiler™ is a comprehensive cardiac safety panel that includes each of the key cardiac channels, providing a robust, cost-effective approach to cardiac liability testing.
Many withdrawn drugs have been shown to block the human ether-a-go-go (hERG) channel, delaying repolarization of the cardiac action potential and leading to prolongation of the QT interval on an electrocardiogram. This can potentially initiate the arrhythmia known as Torsades de Pointes (TdP) with fatal consequences. While hERG is an important factor for cardiac liability, it is not the only factor. Excitation and relaxation of cardiac muscle is regulated by a variety of different ion channels. Some of these channels are genetically linked with long QT syndrome, suggesting that their modulation by drugs could also produce life-threatening arrhythmias independently of hERG. Conversely, a number of relatively potent hERG channel blockers do not induce TdP. Many of these drugs (e.g. verapamil, amiodarone) have mixed channel blocking action which may ameliorate the effects of hERG blockade. Thus, hERG screening alone may be insufficient to flag potential cardiac liability. Conversely, abandoning promising compounds based on hERG blockade alone may result in failing potentially safe clinical drugs.
In support of this philosophy, a recently output of the Cardiac Safety Research Consortium (CSRC) was a proposed shift in cardiac safety assessment to include a Comprehensive in vitro Proarrhythmia Assay (CiPA). CardiacProfiler™ services as well as our related cardiotoxicity assays using human cardiomyocytes fit into this emerging paradigm.
Advantages of Cardiac Risk Profiling with Eurofins:
- Suite of cardiac ion channels with relevant association with Long QT syndrome
- Only provider licensed to offer an Cav1.2 L-type calcium channel
- PrecisION® cell lines recombinantly expressing human channels ensure meaningful high-quality, reproducible results you can trust
- CardiacProfiler™ service offered on a fixed schedule every three weeks
CardiacProfiler™ Services Panel
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Figure 1. Several ion channels involved in mediating the cardiac action potential have also been found to be genetically associated with long QT syndrome.
Figure 2. Profiling of cisapride (A), an inducer of long QT, and verapamil (B), a non-inducer, via CardiacProfiler™ services, identified that blocking hERG will not always correlate with cardiotoxicity if modification of other channel activity can compensate.