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Ion Channel High Throughput Screening

Metrion Biosciences and Assay.Works have formed a partnership to provide high-throughput screening capabilities for ion channel drug discovery

Robust, reliable data to accelerate and validate your drug discovery programmes

An introduction to Metrion’s Ion Channel High Throughput Screening

Metrion has extensive experience of providing high quality biology services for ion channel targets.

Our team offers:
• Exceptional ion channel electrophysiology and drug discovery expertise
• A team of experienced cell biologists to create novel cell lines
• High quality, cost-effective compound screening
• Detailed characterisation of lead compounds in a range of high quality assays
• Translational services including confirmation of efficacy in stem cell and other phenotypic models
• Rapid reporting and data interpretation by experienced ion channel experts

Assay.Works offers unique and non-redundant small molecule sets which can be combined as modular high-throughput screening decks:
• 150,000 commercially available compounds with freedom to operate
• Carefully selected by experienced chemists lead-likeness and chemotype filtered
• Molecular mass and purity verified

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Multi-assay High-throughput Drug Repurposing Screen:
KCNC1 Case Study

Overview

Eliana is a two-year-old from Canada with a de novo mutation (V434L) in her KCNC1 gene which encodes for the Kv3.1 channel in central nervous system neurons such as cerebellar neurons and GABAergic interneurons. The mutation manifests as a variety of neurological disorders which can include myoclonic epilepsy and ataxia due to K+ channel mutation, developmental epileptic encephalopathy (DEE), or hypotonia, depending on the specific variant. Although Eliana does not exhibit typical DEE, she suffers from hypotonia, cortical-visual impairment, vertical nystagmus, and global delays. 

Eliana’s parents founded the KCNC1 Foundation, where 14 different genetic variants from 36 patients have been registered. Of these patients, 25% share the A421V variant, 12.5% share the R320H variant, a few exhibit the V432M variant, and the remaining variants are seen in 1-3 patients. Together with their partners, the foundation decided to undertake drug repurposing studies to quickly identify safe and cost-effective therapies for Eliana. The KCNC1 foundation collaborated with Metrion Biosciences, where manual and automated (Qube) patch-clamp techniques and Fluorescent Imaging Plate Reader (FLIPR) high throughput screens (HTS) against the mutant channel were performed to identify hit compounds.

Small Molecule Library

Figure 1: Physico-chemical property profile according to Lipinski’s Rule of 5 (left); Prediction of compound properties and drug-like features: Colloidal Aggregation, Permeability, Bioavailability, Solubility, PAINS.

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Modular Screening Decks for Various Applications and Budgets

Figure 2: Compound sets and diversity metrics based on Bemis-Murcko clusters.

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Ion Channel HTS: Metrion’s High Quality Platforms

Ion channel drug discovery is reliant on sophisticated screening platforms. Metrion employs electrophysiology platforms to deliver high quality recordings and data alongside the latest liquid handling capabilities. We also offer fluorescence-based screening capabilities suitable for HTS campaigns and follow-up profiling.

Fluorescence and luminescence
  • FLIPR Penta
Automated electrophysiology
  • Qube 384
  • QPatch-48 (x2) and QPatch-II 
Characterisation of compound activity
  • Manual Patch Clamp (x8)
  • Multi-Electrode Array and Impedance Recording
Liquid Handling
  • Agilent Bravo
  • Tecan D300e
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Metrion’s Ion Channel Screening Resource library

Metrion Biosciences Ion Channel Screening Icon Large 01 Ion Channel Screening Resources
Publications
Videos and Presentations
Posters
Application notes and resources
High Throughput Screening at Metrion Brochure

Metrion’s High Throughput Screening Brochure

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Let’s work together

What are your specific ion channel screening requirements?

If you have any questions, or would like to discuss your project, we will put you directly in touch with a member of our scientific team. Contact us today to discover more.