Using Qube 384, we profiled a panel of NaV inhibitors across species, providing valuable translational insight early in analgesic drug discovery.
NaV1.8 is a clinically validated target for non-opioid pain therapeutics. NaV1.8 channels are highly expressed in peripheral sensory neurons and play a critical role in the generation and transmission of pain signals. Selective inhibition of NaV1.8 has the potential to deliver analgesia while avoiding many of the safety and dependency concerns associated with opioid therapies.
Metrion provides industry-leading ion channel research and electrophysiology services supporting drug discovery programmes across pain, neuroscience, cardiovascular and safety pharmacology applications. Our validated recombinant human NaV1.8 assay combines gold-standard manual patch clamp and automated patch clamp technologies to support hit identification, lead optimisation, candidate selection and translational pharmacology studies. These studies provide key pharmacological data to support compound prioritisation and progression of next-generation non-opioid pain therapeutics.
Figure 1: Manual patch clamp recordings confirmed expected hNaV1.8 biophysical properties, with activation and inactivation parameters consistent with published values.
Figure 2: Left: example 1-t plot. Right: Normalised current. Vehicle recordings in the presence of 0.3 µM TTX showed minimal current rundown, demonstrating robust assay stability on the Qube.
Figure 3: VX-548 displayed greater potency at human than rat NaV1.8, whereas PF-04531083 showed similar potency across species, highlighting important orthologue differences.
NaV1.8 is a voltage-gated sodium channel predominantly expressed in peripheral sensory neurons. It plays a critical role in the initiation and transmission of pain signals and has emerged as an important target for the development of non-opioid pain therapies.
Selective inhibition of NaV1.8 has the potential to reduce pain while avoiding many of the safety and dependency concerns associated with opioid-based treatments. Clinical and preclinical studies have demonstrated the importance of NaV1.8 in acute, inflammatory and neuropathic pain pathways.
Metrion's NaV1.8 assays can be used to evaluate small molecules, peptides and other therapeutic modalities designed to modulate NaV1.8 channel activity. Assays can support screening, profiling and lead optimisation programmes.
Metrion offers NaV1.8 studies using gold-standard manual patch clamp electrophysiology as well as QPatch and Qube automated patch clamp platforms. This enables both detailed mechanistic investigations and higher-throughput screening campaigns.
The assays have been validated using detailed biophysical characterisation, current stability assessments and pharmacological profiling with established NaV1.8 inhibitors, including PF-04531083 and VX-548. Assay performance has been demonstrated across manual patch clamp, QPatch and Qube platforms.
Yes. Metrion's validated NaV1.8 assays are routinely used to support hit confirmation, potency determination, structure-activity relationship studies, lead optimisation and candidate selection activities.
Yes. Manual patch clamp studies can provide detailed information on channel activation, inactivation, state dependence and inhibitor pharmacology, helping researchers better understand compound mechanism of action.
Automated patch clamp platforms such as QPatch and Qube provide robust, reproducible electrophysiology data with increased throughput. These systems are particularly well suited to screening and lead optimisation programmes that require evaluation of larger compound sets.
Metrion combines extensive ion channel expertise with validated assay platforms, gold-standard electrophysiology capabilities and experienced scientific teams. We support clients throughout the drug discovery process, from early screening through to candidate selection and translational pharmacology studies.
The Qube and QPatch automated patch clamp systems are developed by Sophion Bioscience, a leading provider of electrophysiology instrumentation used throughout the pharmaceutical, biotechnology and CRO sectors. These platforms are widely adopted for ion channel research and drug discovery, enabling the generation of high-quality electrophysiology data for compound screening, pharmacological profiling and lead optimisation studies. Metrion uses both QPatch and Qube systems to provide flexible screening solutions ranging from detailed pharmacological investigations to higher-throughput compound evaluation.
Using Qube 384, we profiled a panel of NaV inhibitors across species, providing valuable translational insight early in analgesic drug discovery.
We explore hNav1.9's unique fast and slow inactivation properties using Qube 384 and QPatch 48 platforms, helping to build more predictive screening assays for state-dependent inhibitors.