High-throughput Na_V1.9 assay to advance pain drug discovery research

Boost screening efficiency for pain targets

Ion channels are a major class of drug targets for modulating pain transmission and controlling chronic pain. The voltage-gated sodium channel, Na_V1.9, has been identified as a critical component of pain signalling. While Na_V1.9 holds great promise as a non-opioid pain target, the discovery and development of new chemical entities has been hampered by the availability of robust cellular reagents suitable for high-throughput electrophysiology. The global chronic pain treatment market was valued at $88.2 billion in 2023 and is projected to reach $173.4 billion by 2033, growing at a 7.0% CAGR. Neuropathic pain, a major segment of this market, represents around 31.6% of the total.¹

Metrion has addressed this challenge with the development of robust stably expressing Na_V1.9 cell lines (human and rat) which have been validated on the QPatch 48 and Qube 384 electrophysiology platforms. This enables:

Stable expression ensures consistent and reproducible results: Stable expression of Na_V1.9 (human and rat) means assays are more reliable, supporting high-quality screening and dependable pharmacological data.
High-throughput, cost-efficient screening campaigns: Critical for early-stage drug discovery.

Drug discovery enabled in an underexplored but clinically relevant area: Because of technical hurdles, Na_V1.9 has been under-targeted despite its relevance to chronic pain. Metrion’s validated assays now make it accessible for screening, opening new avenues for novel pain therapeutics.
Improved translational relevance: Having both human and rat cell lines allows for cross-species pharmacology studies, improving translational relevance and supporting regulatory submissions down the line.

Our unique approach to Na_V1.9 drug discovery for faster, smarter, cost-effective screening that will unlock ROI

With over a decade of electrophysiology expertise, the Na_V1.9 assay, alongside Metrion’s unique combination of ion channel expertise, bespoke assays and pain research services, enables researchers to overcome traditional limitations of Na_V1.9 screening, to generate reproducible and decision-ready data.

The business case is clear for organisations looking to rapidly meet project milestones and unlock ROI in pain drug discovery:

Shorter timelines: High-quality screening assays accelerate project milestones.
Lower costs: Reliable screening data to robustly support medicinal chemistry.
Cost-effective outsourcing: Rapid, expert data interpretation ensures confident advancement of promising compounds.
High confidence in Na_V1.9 screening cascade (Figure 1):
- Identify high quality hits
- Accelerate hit-to-lead discovery
- Investigate mechanism of action via translational assays

Figure 1. Example of Metrion's Na_V1.9 screening cascade.

Comprehensive suite of services lead by drug discovery experts sets Metrion apart

Alongside our highly experienced electrophysiologists, Metrion’s Na_V1.9 drug discovery assays, in combination with other pain research related services, sets the Metrion offering apart from others by combining the following to support our customers’ discovery needs:

Leadership team with over 100 years’ experience in drug discovery research
High-throughput hit finding using a robust human Na_V1.9 cell line
Assays suitable to support hit-to-lead and lead optimisation
Rat Na_V1.9 assay for species confirmation
Complete panel of sodium channels for selectivity profiling including other pain targets such as Na_V1.7 and Na_V1.8
Large collection of off-target counter screens including CiPA panel for cardiac safety risk assessment
Access to mechanistic and translational assays using the manual patch clamp technique with rat DRG neurons

Let's elevate your pain drug discovery together

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Need for reliable screening assays: Overcoming challenges in studying Na_V1.9

Challenges in studying Na_V1.9

Despite its importance in pain research, Na_V1.9 remains one of the most difficult sodium channel targets to prosecute due to:

Functional expression challenges: Difficulty in expressing Na_V1.9 in stable heterologous systems
Unique biophysical properties: Activation and inactivation kinetics of Na_V1.9 require voltage-control only offered by patch clamp techniques, including automated electrophysiological systems

High quality reproducible data

Metrion has overcome these challenges by developing robust Na_V1.9 cell lines which have been validated using the QPatch 48 and Qube 384 providing high quality reproducible data.

Our validated, high-throughput Na_V1.9 screening solution delivers consistent and accurate results. Key advantages:

High-throughput Na_V1.9 screening for rapid compound testing: The CHO-hNa_V1.9 cell line, developed in-house by Metrion, enables automated patch-clamp screening using the Qube 384 platform. This system allows rapid testing of large compound libraries and hit-to-lead support.
Reliable Na_V1.9 data, fewer setbacks: The stable and robust expression of Metrion’s Na_V1.9 cell line ensures high reproducibility and low assay variability. We have demonstrated high sensitivity, robustness and accuracy of Na_V1.9 screening data during the assay development with the testing of tool compounds and compound plates randomly spiked with a Na_V1.9 inhibitor.

These enhancements place Metrion at the forefront of Na_V1.9 drug discovery.

Example family of current recordings of hNaV1.9 using the Qube automated electrophysiology platform (A). Current-voltage relationship of hNaV1.9 (B).

Figure 2. Example family of current recordings of hNaV1.9 using the Qube automated electrophysiology platform (A). Current-voltage relationship of hNaV1.9 (B).

Figure 3. Pharmacological assessment of human Na_V1.9. Current traces and concentration response curves for TC-N 1752, obtained using Qube 384.

Download poster: Development of a high-throughput automated electrophysiology assay for human Nav1.9 inhibitor screening

Understanding Na_V1.9: A critical pain target

Role of Na_V1.9 in sensory neurons

Na_V1.9 is a voltage-gated sodium channel predominantly expressed in peripheral sensory neurons, where it plays a vital role in pain signalling. These channels contribute to the excitability of nociceptive neurons directly influencing pain pathways. The unique biophysical properties of Na_V1.9 plays a key role in regulating the threshold for neuronal firing and is seen as an attractive target for non-opioid pain management.

Genetic mutations and pain disorders

Na_V1.9 has been linked to various pain disorders through genetic mutations leading to both chronic pain syndromes and insensitivity to pain. These discoveries further support the significance of Na_V1.9 in pain physiology and the importance of this particular sodium channel subtype as a pain target.

Advantages of automated patch clamp technology in Na_V1.9 screening

Leading the way in Na_V1.9 hit finding, Metrion has exceptional expertise in automated electrophysiology platforms, which delivers:

Greater throughput: The ability to screen thousands of compounds in a fraction of the time
Improved data consistency: Reduced variability and enhance reproducibility
Reduced timelines: Lower resource requirements with faster turnaround providing a more cost-effective programme

Why researchers should choose Metrion to support their Na_V1.9 programmes

Uniquely positioned as a leader in ion channel drug discovery, Metrion scientists have extensive experience in neuroscience, in particular pain, gained from both academic and industry environments. By partnering with Metrion, customers benefit from:

Industry-leading expertise: Exceptional team of electrophysiologists, lead by highly skilled experts with extensive knowledge of pain research and ion channel pharmacology
Fast and reliable data reporting: Accelerating the pace of drug discovery with rapid turnaround times
Comprehensive scientific support: Providing detailed data interpretation and expert guidance
State-of-the-art technology: Access to automated patch clamp systems for high-throughput screening
Gold standard electrophysiology: Experts in all in vitro manual patch clamp configurations
Extensive collection of ion channel cell lines: Access to broad range of ion channel targets for selectivity assessment, including CiPA panel
Customised research solutions: Tailored services designed to meet specific project needs in both in vitro and translational assays
Translational assays: Validation of lead compounds in sensory neurons

Let's elevate your pain drug discovery together

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Contract research services for preclinical drug discovery beyond Na_V1.9

Metrion continues to lead the way in ion channel research. Our Na_V1.9 capabilities represent a significant advancement in pain drug discovery. By addressing key challenges associated with Na_V1.9, the use of cutting-edge automated patch clamp technology and rodent translational models, Metrion is ready to support your projects to identify new pain therapies.

Beyond Na_V1.9, Metrion offers an extensive portfolio of ion channel screening services, including validated assays for the full Comprehensive in vitro Proarrhythmia Assay (CiPA) panel for cardiac safety assessment: hERG, hNav1.5, hCav1.2, hKir 2.1, hKv 4.3/KChIP, hKv LQT1/minK, Late Nav1.5.

This breadth allows customers to consolidate their ion channel research needs with a single provider, streamlining project management and communication.

Apply Metrion’s expertise to your Na_V1.9 research

Reference

1. https://market.us/report/chronic-pain-treatment-market/

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High-throughput Na_V1.9 assay to advance pain drug discovery research

Boost screening efficiency for pain targets

Our unique approach to Na_V1.9 drug discovery for faster, smarter, cost-effective screening that will unlock ROI

Comprehensive suite of services lead by drug discovery experts sets Metrion apart

Let's elevate your pain drug discovery together