Cardiac safety assessment is a critical component of modern drug discovery. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative was developed to improve the prediction of drug-induced proarrhythmic risk by combining multi-ion channel screening, in silico modelling and human-relevant cardiac electrophysiology data.
Metrion provides specialist CiPA screening services to support the assessment of proarrhythmic liability in new drug candidates. Using highly validated cardiac ion channel assays and industry-leading electrophysiology platforms, we generate high-quality data that supports compound progression decisions, cardiac risk assessment, regulatory submissions and in silico cardiac safety modelling.
Our portfolio includes assays covering the full CiPA ion channel panel, together with additional cardiac ion channels relevant to heart rate regulation and cardiac electrophysiology. Data generated using our platforms are suitable for incorporation into in silico action potential models, a key component of the CiPA framework.
Metrion's validated assay portfolio covers all ion channels recommended within the CiPA framework, enabling comprehensive assessment of compound effects on cardiac electrophysiology. This portfolio includes:
In addition to the core CiPA panel, Metrion offers screening against additional cardiac ion channels, including:
These channels play important roles in regulating heart rate and atrial repolarisation and can provide valuable additional information during cardiac safety assessment programmes.
Table 1. Assays covering a broad range of human cardiac ion channels, including the full CiPA panel.
Metrion was an early and active participant in the CiPA ion channel high-throughput screening (HTS) sub-team and played a key role in advancing the initiative. We were also an active member of the Health and Environmental Sciences Institute (HESI) Cardiac Safety Committee, collaborating with industry, regulatory and scientific stakeholders to improve the accuracy, consistency and predictive value of cardiac safety assessment.
Our contributions included:
This experience gives clients access to one of the most experienced teams in CiPA-related cardiac safety screening.
Our validated CiPA screening services provide:
By combining validated assays, advanced electrophysiology platforms and decades of ion channel expertise, Metrion helps clients generate the high-quality data needed to support compound progression decisions, regulatory submissions and modern CiPA-based cardiac safety assessment strategies.
Metrion provides potency assessment against individual cardiac ion channels using both single-point and concentration-response study designs.
Assays are available using:
These high-fidelity electrophysiology platforms generate robust and reproducible data suitable for incorporation into in silico cardiac action potential models and broader CiPA-based cardiac safety assessment strategies.
Figure 1a. CiPA ion channel panel – hERG
Figure 1b. CiPA ion channel panel – NaV1.5
Figure 1c. CiPA ion channel panel – CaV1.2
Figure 1d. CiPA ion channel panel – KCNQ1 KCNE1
Figure 1e. CiPA ion channel panel – Kir2.1
Figure 1f. CiPA ion channel panel – KV4.3
Cardiac ion channel assays have been developed and optimised for key channels involved in cardiac electrophysiology, including hERG, NaV1.5 and CaV1.2.
Studies can be performed using the QPatch48 or Qube automated patch clamp platforms, or manual patch clamp, depending on project requirements. The Qube supports high-throughput screening while maintaining the data quality required for cardiac safety decision-making and in silico modelling.
By evaluating compound activity across multiple cardiac ion channels, Metrion helps clients identify potential electrophysiological liabilities, characterise cardiac risk profiles and support safer candidate selection.
Metrion has pioneered the development of a robust dynamic hERG assay suitable for automated patch clamp platforms, enabling physiologically relevant assessment of hERG pharmacology at screening scale.
This assay has been used to generate critical data supporting refinement of the FDA's in silico qNet model, helping improve the prediction of drug-induced cardiac risk.
The assay incorporates the challenging Milnes dynamic voltage protocol, enabling a more physiologically relevant assessment of compound interactions with the hERG channel than traditional static voltage protocols.
The Milnes assay is a specialised dynamic voltage-clamp protocol developed to assess hERG channel function under conditions that more closely mimic physiological cardiac electrophysiology.
Unlike traditional static voltage protocols that measure channel activity at fixed voltages, the Milnes protocol applies a dynamic voltage waveform that allows researchers to evaluate compound interactions across a broader range of voltages and time points.
This approach provides deeper insight into hERG pharmacology and supports improved prediction of proarrhythmic risk.
When implemented on automated patch clamp platforms such as the Qube, the Milnes dynamic hERG assay enables efficient screening of larger compound sets while maintaining the quality required for cardiac safety assessment.
A key objective of the CiPA initiative is the integration of ion channel pharmacology data into predictive in silico cardiac models.
Metrion's validated cardiac ion channel assays generate high-quality potency data suitable for use in:
By combining extensive ion channel expertise with validated electrophysiology assays, Metrion helps clients generate the data required to support modern cardiac safety assessment strategies.
The Comprehensive In Vitro Proarrhythmia Assay (CiPA) is a cardiac safety assessment framework that combines multi-ion channel screening, in silico modelling and human-relevant cardiac electrophysiology data to improve prediction of proarrhythmic risk.
CiPA improves cardiac safety assessment by evaluating compound effects across multiple cardiac ion channels and integrating these data into predictive in silico models. This approach provides a more comprehensive assessment of proarrhythmic risk than reliance on hERG screening alone.
The core CiPA panel includes hERG, peak and late NaV1.5, CaV1.2, KCNQ1/KCNE1, Kir2.1 and KV4.3.
Metrion offers CiPA screening using Sophion QPatch48, Sophion Qube and gold-standard manual patch clamp electrophysiology.
Metrion's dynamic hERG assay uses the Milnes voltage protocol to provide a more physiologically relevant assessment of compound interactions with the hERG channel and generate data suitable for advanced cardiac risk modelling.
hERG screening assesses compound effects on a single cardiac ion channel associated with QT prolongation risk. CiPA screening evaluates multiple cardiac ion channels and incorporates in silico modelling to provide a broader assessment of proarrhythmic liability.
The Qube and QPatch automated patch clamp platforms are developed by Sophion Bioscience, a leading provider of electrophysiology instrumentation for ion channel research, drug discovery and safety pharmacology.
Biologic modalities may offer opportunities to achieve levels of subtype selectivity that can be difficult to obtain using traditional small molecules, particularly across closely related ion channel family members. This may enable more precise modulation of disease-relevant targets while potentially reducing unwanted off-target activity.
We’re proud to introduce two scientific leaders whose expertise is helping advance ion channel drug discovery and pain research: Eddy Stevens, PhD, Chief Scientific Officer, and Tony Rush, PhD, Director of Neuroscience and Commercial Operations.