Integrated drug discovery adds significant value to your programmes by not only developing but also de-risking ion channel modulators throughout their progression towards nomination for clinical development. By utilising cutting-edge techniques, rigorous testing, and comprehensive validation processes, we help to ensure that the compounds developed are both safe and efficacious. Our multidisciplinary approach minimises risks and increases the likelihood of nomination of successful candidates.

Metrion’s deep know-how, extensive breadth of services, and years of experience in ion channel research enable us to navigate complex challenges during the key stages of the drug discovery process. During each step of your journey with Metrion, our dedicated team will provide tailored solutions that accelerate your research and bring compounds closer to clinical development. We are committed to guiding your drug discovery research program with precision, successfully achieving milestones in a cost-effective manner, and ultimately enhancing the therapeutic potential of your drug candidates.

Bringing together experts in different disciplines provides our clients with a fully integrated drug discovery service.

Highly experienced integrated drug discovery team

Our experience will guide your drug discovery research programme successfully and cost effectively. We offer wide ranging expertise and pre-validated industry leading assays for ion channels. Our leadership team has published ~ 150 peer-reviewed articles and has been involved in drug discovery programs at respected pharma and biotech companies globally.

Bringing experts together

Our highly experienced interdisciplinary team provides customers with a fully integrated drug discovery service by bringing together experts in:

• Ion channel biology
• Medicinal chemistry
• Specialist chemistry
• Translational biology
• ADMET and DMPK

Our integrated drug discovery service includes initial assay development, custom assay validation and high throughput screening in 384-well plate-based assays. It also comprises giga seal quality automated electrophysiology-based support for medicinal chemistry optimisation of compounds and highly experienced conventional electrophysiology services for profiling of lead compounds. Metrion’s team of expert scientists offer detailed advice and recommendations regarding translational assays such as microelectrode array and impedance measurement.

Alongside trusted partners, Metrion brings:

• A wealth of specialised experience and scientific expertise to help steer your research programme toward a successful, efficient, and cost-effective conclusion.
• Understanding of the importance of precision and reliability in scientific discovery and are dedicated to delivering exceptional results.

Our team is fully equipped to assist you through every phase of the research process, from initial concept to final validation, ensuring the highest standards of quality and efficiency throughout.

A comprehensive suite of industry-leading validated assays has been designed to support your research needs across a broad range of ion channel targets. Our portfolio includes the following assays:

• Voltage-gated ion channels, essential for exploring cellular excitability and understanding the mechanisms behind action potential propagation in excitable cells. These channels play a crucial role in various physiological processes, including muscle contraction and neurotransmission.
• Ligand-gated ion channels, which are vital for studying synaptic transmission and the regulation of intracellular signalling pathways. These channels respond to neurotransmitters and other ligands, enabling rapid cellular responses to environmental changes.
• Multimodal transient receptor potential (TRP) channel assays, providing insights into the sensory functions of these channels, which are involved in detecting and responding to diverse stimuli, such as temperature, pH, and mechanical forces.Assays for two-pore domain ‘leak’ channels, which are involved in regulating the resting membrane potential and ion homeostasis across cell membranes. These channels are important for cellular volume control and overall homeostasis.
• Inward rectifier channels, which play a key role in maintaining the stability of the resting membrane potential and controlling the flow of ions into the cell, which is essential for maintaining cellular excitability and function.
• Hyperpolarisation-activated cyclic nucleotide-gated (HCN) ion channel assays, which are crucial for studying pacemaker activity, particularly in heart cells and neurons, where these channels are involved in regulating rhythm and electrical activity.

Accurate, reliable and cost-effective drug discovery

Through our advanced and comprehensive assay portfolio, Metrion advances your research with the tools, insights, and expertise necessary to drive scientific advancements. With a focus on accuracy, reliability, and cost-effectiveness, we work alongside our partners to ensure your research programme is both successful and economically viable, enabling you to make meaningful contributions to the field of ion channel drug discovery.

Customised integrated drug discovery research programmes

Our extensive experience means we are very happy to discuss integrated drug discovery research programmes for all types of ion channels.

Access to the highest quality small molecule libraries

Customers can access a high-quality library of small molecules. This is in addition to a comprehensive and diverse range of stable cell lines and comprehensively validated assays, plus a choice of assay platforms to suit the requirements of individual customers during the hit identification stage of a discovery programme. Computational chemistry expertise is accessible for knowledge-based selection of a screening deck. Alternatively, Metrion’s highly specialised team can perform diverse screens using the Enamine or Assay.Works libraries alone or supplement them with customer molecules or libraries accessed via compound vendors.

Building appropriate screening cascades

Advice and building of appropriate screening cascades are available for customers who do not possess significant experience of the ion channel target class. Alternatively, we can work together with experienced customers to maximise their chances of success for this challenging target class, supported by Metrion’s extensive ion channels knowledge and expertise.

Maximise your efficiency through integrated drug discovery

Metrion’s integrated drug discovery service is built on a foundation of close collaboration and continuous interaction with our customers. We work closely with you to thoroughly define and refine the profile of compounds that are most suitable for your specific therapeutic focus.

We recognise that each drug discovery project is unique. Our goal is to ensure that the compounds we develop are tailored to meet the precise needs of your research and therapeutic objectives. This process begins with:

• A comprehensive analysis of the desired drug-like properties.
• Optimisation of each compound to maximise efficacy while minimising potential side effects.

Beyond optimising individual compound properties, we collaborate with customers to design and implement assays within the screening cascade. Our approach ensures that:

• Each assay is tailored to generate the most relevant and actionable biological data.
• The underlying biology of the target and the specific therapeutic context are well understood.
• Assays are designed to measure key pharmacological characteristics, such as the block of ion channels in specific states, providing critical insights into mechanism of action and potency.

This level of detail ensures that the screening process is both informative and efficient, facilitating the identification of the most promising candidates for further development.

Through this collaborative and highly tailored approach, our integrated drug discovery service enables the creation of well-defined, highly relevant compound profiles. This accelerates the discovery of novel therapies while minimising risk and maximising success.

High quality ion channel assays to drive enhancement of compound potency

Strong emphasis is placed on maximising the efficiency of the design and synthesis of new analogues. This enables rapid structure-activity relationship (SAR) determination at an early stage, providing appropriate high-quality assays to drive the enhancement of compound potency and selectivity properties.

Key elements of our approach include:

• Early assessment of Absorption, Distribution, Metabolism, and Excretion (ADME) properties.
• Ranking hit compounds and/or hit series for progression to lead optimisation.
• Identifying and mitigating potential risks before advancing compounds further in development.

As each screening program progresses toward lead optimisation, our collaborations provide invaluable access to expert toxicologists who specialise in:

• Designing and conducting experiments to thoroughly characterise potential toxicity concerns.
• Assessing safety risks early, whether they arise from on-target interactions or other observed issues.
• Providing a comprehensive understanding of the compound's toxicological profile.

Our focus on mechanistic toxicology at this early stage is key to:

• Identifying potential toxic effects and understanding their underlying causes.
• Generating critical data to inform molecule design, optimising compounds to minimise toxicity while maintaining or enhancing efficacy.
• Supporting candidate selection by prioritising molecules with the best overall therapeutic potential while mitigating risks.

Additionally, we provide expert guidance on translational risk assessment, ensuring:

• Safety and efficacy profiles align with clinical expectations.
• Informed decision-making about candidate progression to reduce the risk of failure in later stages.
• Selection and development of biomarker assays to ensure reliable biological translation throughout the discovery program.

By integrating toxicology expertise into the lead optimisation process, we help accelerate the progression of safe, effective drug candidates, offering a seamless and well-rounded approach to drug discovery.

High quality ion channel drug discovery assays for efficiently driving medicinal chemistry

For ion channel targets, our team has extensive experience supporting customer integrated research programmes and a track record of successful delivery of high-quality assays, long term delivery of screening data to defined timelines to efficiently drive medicinal chemistry and has delivered clinical candidates for our customers. For an initial discussion and to learn more about Metrion’s extensive suite of services, please contact us.