Specialist, cost efficient, ion channel high-throughput screening
Assays to support hit identification, hit-to-lead, lead optimisation and selectivity profiling
The high-throughput screening (HTS) of vast numbers of compounds is pivotal to the drug discovery process. It is often an expensive, timely, process which can return false positive results. What sets us apart is our specific high-throughput screening knowledge and experience across multiple ion channel targets.
By working with our ion channel HTS specialists you will have access to a dedicated and highly experienced team, with experience including high-throughput ion channel screening to support HTS campaigns, hit identification, hit-to-lead, lead optimisation and follow-up selectivity profiling. Custom cell line generation, assay development and optimisation are also provided in-house.
Once we have run your project, we will analyse the data, communicate the results and support your decision making to best inform your screening strategy.
Our complementary phenotypic and translational assays enable further detailed characterisation of your lead compounds. Read about our small molecule library and modular screening decks to suit your project and budget.
B. Kinetic trace showing example of compound profiles (red) relative to 0% inhibition (green) and 100% inhibition (blue) control wells. Read the drug repurposing HTS case study about a recent project researching a rare de novo variant in the KCNC1 gene.
Access to Enamine and Assay.Works compound libraries
To support your medicinal chemistry programmes and structure-activity relationship (SAR) studies, we offer access to commercially available compound libraries from Enamine and Assay.Works.
Case study
Multi-assay High-throughput drug repurposing screen:
KCNC1
Overview
Our approach enabled a long-term Kv1.3 screening project to expand medicinal chemistry SAR and successfully identify selective small molecule modulators by accessing high quality APC and ion channel expertise. Through this long-term collaboration with a pharmaceutical company, Metrion delivered: exceptional long-term reliability of the optimised primary target screen and counter-screen assays over the course of two years, bespoke development of cell lines, including support of complete gene family selectivity and species selectivity studies, wider selectivity studies including extended cardiac (CiPA) panel screening, and exploration of mechanism of action (e.g. closed, open or inactivated state block).
Small molecule library and modular screening decks to suit your project and budget
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.
Figure 2: Compound sets and diversity metrics based on Bemis-Murcko clusters.
A combined, flexible, approach for your high-throughput ion channel screening project
By screening across multiple platforms we offer flexibility and use technology and automated processes in synergy to progress your project as efficiently and cost-effectively as possible.
Ion channel screening resource library
Ion Channel Screening ResourcesPublications
- Ion Channel Drug Discovery and Modern Medicine.
- Ion Channel Discovery – Partnering to Access Specialized Expertise.
- Recent advances in electrophysiology-based screening technology and the impact upon ion channel discovery research.
- Clathrodin, hymenidin and oroidin, and their synthetic analogues as inhibitors of the voltage-gated potassium channels.
- Novel K+ Channel Targets in Atrial Fibrillation Drug Development – Where Are We?
- Human Electrophysiological and Pharmacological Properties of XEN-D0101: A Novel Atrial-Selective Kv1.5/IKur Inhibitor.
Videos and Presentations
- Designing multiple assay protocols for ligand gated ion channels using the stacked-tip feature on the Patchliner and SP384i platforms
- The benefits of targeting ion channels for pain and some of the hurdles in developing successful ion channel modulators.
Posters
- Identification of Novel Scorpion Venom Peptide Inhibitors of the Kv1.3 Ion Channel and their Potential as Drug Discovery Leads for Human T-Cell Mediated Disease.
- The development of a set of novel small molecule inhibitors of the Kv1.3 ion channel.
- A drug discovery collaboration between Japanese pharma and a UK SME CRO successfully developed novel small molecule inhibitors of the Kv1.3 channel to treat autoimmune disease.
Application notes and resources
- ASIC1a Ligand Gated Ion Channel Assay (App Note)
- Investigating the correlation between thallium flux and automated patch-clamp for ion channel activators.
- Identification of novel ion-channel binders: TRPA1 antagonist case study.
- The development of a set of novel small molecule inhibitors of the Kv1.3 ion channel.
Cardiac Safety Screening Resources- Cross-site and cross-platform variability of automated patch clamp assessments of drug effects on human cardiac currents in recombinant cells.
- A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm
- The Nav 1.5 Late Current in WT and Nav 1.5 ΔKPQ Mutant Channels: An Automated Patch Clamp LQT3 Electrophysiological Assay Comparison. Safety Pharmacology Society Virtual Meeting 2020.
- NaV1.5-ΔKPQ late INa current properties and pharmacology on the SyncroPatch 384i
Neuroscience Resources- Recent advances in targeting ion channels to treat chronic pain.
- Marc Rogers (Metrion Director and Former CSO) takes part in a collaborative webinar with Nanion Technologies entitled “Validation and optimization of automated patch clamp voltage-gated Ca2+ channel assays”.
- Open access to the KCNQ channel: Retigabine and second generation M-current openers.
- Development of native and stem cell-derived electrophysiological assays for neurotoxicology screening and translational drug discovery
- Characterization of Endogenous Sodium Channels in the ND7-23 Neuroblastoma Cell Line: Implications for Use as a Heterologous Ion Channel Expression System Suitable for Automated Patch Clamp Screening.
- Optimising a difficult Nav1.8 cell line assay for automated patch clamp screening. Ion Channel Retreat, Vancouver, 2015
- Synthesis and biological evaluation of piperazine derivatives as novel isoform selective voltage-gated sodium (Nav) 1.3 channel modulators
- Action of Clathrodin and Analogues on Voltage-Gated Sodium Channels
- Novel state-dependent voltage-gated sodium channel modulators, based on marine alkaloids from Agelas sponges
- Ligand- and structure-based virtual screening for clathrodin-derived human voltage-gated sodium channel modulators
Translational Assay Resources- The role of Nav1.7 in human nociceptors: insights from human induced pluripotent stem cell-derived sensory neurons of erythromelalgia patients
- Assessment of human induced pluripotent stem cell-derived cardiomyocytes for evaluating drug-induced arrhythmias with multi-electrode array
- Development of an impedance based screening assay for cardiac safety and cardiotoxicity detection in stem cell derived cardiomyocytes
- Validation of an impedance-based phenotypic screening assay able to detect multiple mechanisms of chronic cardiotoxicity in human stem cell-derived cardiomyocytes
- Electrophysiological characterisation of Cellular Dynamics International ventricular iCell2 iPSC-derived cardiomyocytes
- Functional characterisation of human iPSC-derived atrial cardiomyocytes
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.