I am currently studying Biomedical Sciences at the University of Manchester. Through my previous years of education, I enjoyed studying biology and engaging in practical experiments, particularly those with clinical relevance, which ultimately guided my degree selection. With Biomedical Sciences I am able to study human biology to a greater depth and also have the opportunity to acquire more laboratory practice and experience.

During the last two years at university, I became interested in the neuroscience and pharmacology modules offered. The modules incorporated molecular biology, exploring existing ion channelopathies and their disease relevance. Ion channel dysfunction has implications in numerous conditions, such as epilepsy or cardiac arrhythmias, giving the research significant importance. Electrophysiological techniques are part of a specialist biological field I have not been previously exposed to, which made the opportunity of a placement with Metrion extremely exciting.

Another reason for choosing Metrion is because they are a specialist ion channel-focussed contract research organisation (CRO), and has service offerings spanning ion channel screening, neuroscience and cardiac safety. Metrion uses automated and manual patch clamp techniques, using specifically developed cell lines. Throughout my industrial placement I will be introduced to a wide range of research projects, learning both specialised electrophysiology and the broader techniques required of a proficient laboratory scientist. This includes the ability to successfully analyse data and form reasonable conclusions.

Assay design and optimisation are essential skills, applicable to every field of science. The adaptability I am learning is a great development opportunity, as assay refinement means you can obtain the most reliable data possible. Additionally, the values of Metrion underpin all of the work that is conducted and the way colleagues work together. Values such as quality and integrity enable the company to function efficiently as a collaborative team. These values are ingrained into the company ethos and create a welcoming environment, allowing for a great opportunity to gain experience as a student in a new area of research. I am thoroughly enjoying my placement and look forward to learning more and embracing the new opportunities for scientific development.

The recent ICH E14/S7B Q&As have provided more clarity on the methodologies that should be employed when conducting a GLP hERG to support and IND filing for a novel clinical compound. This includes the suggestion of three reference compounds (dofetilide, ondansetron and moxifloxacin) that may be used to validate a study where data may be required for use in a Thorough QT (TQT) waiver application.

In this current study GLP hERG data were generated for the three reference compounds using ICH best practices in order to understand intra and inter laboratory variability in the data and to assess a suitable hERG safety margin under these conditions. The analyses used 12 hERG IC₅₀ with a group of 5 data sets from a single laboratory and an additional 7 data sets collected by 6 different laboratories. The data highlight the high degree of concordance of results with respect to both intra and inter laboratory variability with respect to hERG IC₅₀ values. Moreover, the inter-drug differences in potency were used to determine pooled margin variability.

The combined data provided a robust hERG margin reference based on best practice guidelines and consistent exposure denominators (provided in the ICH E14/S7B Training Materials). The sensitivity of the hERG margin thresholds generated using the updated ICH best practices were consistent with the sensitivity described over the course of the last two decades. The data are supportive of using a safety of a 30-fold safety margin as part of a more comprehensive integrated risk assessment, although a more conservative 100-fold margin may be more appropriate where no additional assessment has been made.

Derek J. Leishman, Jessica Brimecombe, William Crumb, Simon Hebeisen, Steve Jenkinson, Peter J. Kilfoil, Hiroshi Matsukawa, Karim Melliti, Yusheng Qu, Supporting an integrated QTc risk assessment using the hERG margin distributions for three positive control agents derived from multiple laboratories and on multiple occasions., Journal of Pharmacological and Toxicological Methods, Volume 128, 2024, 107524, ISSN 1056-8719, https://doi.org/10.1016/j.vascn.2024.107524.

Read the full publication.

Learn about our hERG and GLP hERG services, or contact us to discuss how we can help progress your preclinical drug discovery project.

My 12 month industrial placement at Metrion Biosciences was a truly remarkable experience that has helped me grow both personally and professionally. Choosing to complete a placement year was a big decision for me which was made 100% worth it!

I worked alongside many specialist scientists to understanding the principles of ion channel drug discovery and learning the specific disciplines involved. My main focus over the year was my project: The development and validation of patch-clamp assays to study large conductance calcium-activation potassium (BK) channels.

Additionally, I was lucky enough to work on a variety of ion channels, including IK(KCa3.1), NaV1.5, CaV3.2, KvLQT and TRPML1 using patch-clamp technique, and  had the opportunity to present the poster ‘Development of TRPML1-4A assays across manual, automated patch-clamp, and fluorescence-based platforms’ at a scientific conference.

Overall, this industrial placement has been a valuable and inspiring experience which will benefit me in my final year at the University of Bristol and beyond. I am extremely grateful to the entire Metrion team for welcoming me so quickly and supporting me along the way.

The State of the Art in Secondary Pharmacology and its Impact on the Safety of New Medicines

A team of industry experts conducted an extensive survey to highlight similarities and differences in screening strategies and target panels across the pharmaceutical industry. As a result they identified a number of opportunities for further optimisation within the secondary pharmacology assessment of novel compounds. Read more.

Ion Channels as Targets in Drug Discovery

Eddy Stevens, Metrion’s CSO, had the pleasure of working alongside Gary Stephens, University of Reading, to edit the ‘Ion Channels as Targets in Drug Discovery’ book. The publication examines current ion channel success stories and discusses major drug discovery programs in industry. It also explores cutting-edge translational aspects of current ion channel research. Read more.

Advanced In Vitro Screening of New Drugs for Proarrhythmic Activity

10% of drugs entering Phase I receive FDA approval, with unmanageable toxicity accounting for approximately 30% of IND application clinical failure, with cardiac safety-based discontinuation also being one of the most common reasons for withdrawal of marketed drugs. Read more.

Time is a Critical Factor When Evaluating Oligonucleotide Therapeutics in Human Ether-a-Go-Go-Related Gene Assays

Last year we worked alongside authors from Amgen and published data in support of refining the hERG testing strategy for silencing RNA (siRNA). Read more.

Recent Progress Towards a Potential Treatment for KCNC-1 Related Disorders

18th September 2024.

Find out more and register.

In-Vitro Assessment of Cardiac  Risk in Drug Discovery

Attendees learned how an hiPSC-CM model can help provide clear decision-making data for their project team, avoiding costly issues related to QTc and QRS cardiac liabilities in the clinic. Watch webinar recording and read the Q&A.

Development and Validation of a Dual Modality TREK-1 
Screening Assay

Metrion scientists have developed a robust TREK-1 screening assay on the Qube 384 platform capable of 
identifying both activators and inhibitors of the TREK-1 channel. The optimized screening assay was employed in the successful screening of a venom library against TREK-1, detecting peptides with inhibitory and potentiating modalities. Read more and download application note.

Assays Capable of Detecting TRPML1 Modulators for Drug Discovery

Metrion scientists have generated a stable cell line expressing the lysosomal channel TRPML1 at the cell surface. First we validated this on manual patch-clamp and went on to develop robust assays for our higher throughput screening platforms, Qube 384 and FLIPR Penta, which are capable of detecting TRPML1 modulators for drug discovery. Read more and download poster.

An integrated calcium-imaging and patch-clamp system suitable for selecting specific subsets of neurons for electrophysiology recordings

We detail our collaboration with Scientifica on the optimisation and utilisation of the PatchScope Pro. We first targeted three different TRP channels in rat DRG. Subsequently we focused on TRPM8 which is a multimodal sensor present in 10-20% of DRGs neurons. Read more and download poster.

Fluorescence-based Drug Repurposing Screen of the Potassium Channel, K_V3.1 with V434L Mutation

We demonstrate how a cell line expressing the KCNC1 V434L mutation was generated and validated using biophysical and pharmacological methods, then used to screen approximately 6,800 compounds from The Broad Institute Repurposing Hub to identify inhibitors for potential use in the treatment of patients with this rare mutation. Read more and download poster.

Cambridge Ion Channel Forum

Review of Cambridge Ion Channel Forum 2024

We review the Cambridge Ion Channel Forum (CICF) which took place in May. Read review.

Cambridge Ion Channel Forum 2025

Save the date: 15th May 2025

AstraZeneca DISC, UK

Why outsource to Metrion?

We don’t just deliver high quality data, our team uses their extensive experience to carefully interpret the experimental findings, communicate the results, provide recommendations, and support your decision making to best inform your screening strategy. Contact us to advance your preclinical discovery project.

Two-pore domain K⁺ (K_2P) channels are a family of four-pass transmembrane K⁺ channels that dimerise, as homomers or heteromers, to form a functional K⁺ channel complex capable of regulating membrane potential through a background K⁺ conductance. K_2P channels have widespread tissue expression, and within the nervous system they play a key role in membrane hyperpolarisation and the regulation of neuronal excitability. Moreover, these channels are implicated in a range of neurological disorders, such as pain, depression, epilepsy, mental developmental disorders, and migraine, and therefore represent attractive drug targets for these conditions. 

In this application note, we report the development and optimisation of a TREK-1 functional assay using the Qube 384, an automated patch clamp platform capable of supporting high-throughput screening.

The assay was optimized to identify both activators and inhibitors on the same plate, providing key mechanistic data for high value, limited supply screening libraries such as venom fractions used in this study.

It was a pleasure to present this poster at the FENS Forum. The poster details Metrion and Scientifica’s¹ collaboration on the optimisation and utilisation of the PatchScope Pro². We first targeted three different TRP channels (TRPV1, TRPA1 and TRPM8) in rat dorsal root ganglia (DRGs). Subsequently we focused on TRPM8 which is a multimodal sensor (temperature, pressure, voltage, osmolality) present in 10-20% of DRGs neurons.

Using calcium-imaging, response of DRG neurons to TRPV1, TRPA1 and TRPM8 ligands were tested, where 64% of neurons responded to 10 µM capsaicin, 29% to 30 µM cinnamaldehyde and 13% to 500 µM menthol. Subsequently a compound-application protocol was optimized using repeat applications of 200 µM menthol, suitable for combined calcium-imaging/electrophysiology. TRPM8 expressing neurons were characterized using electrophysiology following initial selection by calcium-imaging (menthol positive), where effects of 200 µM menthol were demonstrated in both voltage-clamp and current-clamp recordings (n=5). This study demonstrates the advantages of the PatchScope system for selecting specific subsets of neurons using calcium-imaging prior to electrophysiology recordings.

1. https://www.scientifica.uk.com.
2. Scientifica’s PatchScope Pro is an integrated electrophysiology rig incorporating an inverted phase-contrast fluorescence microscope, motorised XY stage and PatchStar micromanipulators, suitable for patch-clamp recording. In contrast to other patch-clamp systems, this microscope has a small footprint to maximise use of lab space. The low-noise electrical components are designed specifically for patch-clamp recordings. Fluorescence capability allows identification of cells of interest (e.g. using fluorescent markers or calcium-imaging) and motorisation of the stage means that XY co-ordinates of cells can be stored for subsequent electrophysiology and imaging.

K_v3.1 is a voltage-gated potassium channel encoded by the KCNC1 gene. At the recent SLAS EU meeting, we presented a poster to demonstrate how a cell line expressing the KCNC1 V434L mutation was generated and validated using biophysical and pharmacological methods, then used to screen approximately 6,800 compounds from The Broad Institute Repurposing Hub to identify inhibitors for potential use in the treatment of patients with this rare mutation.

Abstract

The voltage-gated potassium channel, Kv3.1, encoded by the KCNC1 gene is expressed in central nervous system neurons such as cerebellar neurons and GABAergic interneurons.  De novo mutations of KCNC1 can manifest in a variety of neurological disorders, including myoclonic epilepsy, ataxia, developmental epileptic encephalopathy or hypotonia. A recent study identified a particular mutation of the Kv3.1 channel, V434L, which exhibited a shift in the voltage dependence of activation to more hyperpolarised potentials¹. Mutations of the Kv3.1 channel are extremely rare, and there is a lack of effective treatments for disorders associated with Kv3.1 channel mutation. As a result, the KCNC1 Foundation looked to find inhibitors of Kv3.1-V434L variant by screening compounds from the Broad Institute Repurposing Hub library.

Stable cell lines for both the wild-type and mutant Kv3.1 channels were created and confirmation of their biophysical properties was performed using the manual patch-clamp technique. Differences in the effects of two pharmacological tool molecules, 4-AP and AUT1, on the wild-type and mutant Kv3.1 currents were observed with the decision taken to screen the library against the Kv3.1-V434L variant.

A thallium-based fluorescence assay was developed and optimised on the FLIPR^Penta to identify inhibitors of the Kv3.1-V434L variant. The Broad Repurposing Hub library of 6,718 compounds were screened in duplicate at 10 µM.  The screen was robust, with the assay metrics for signal-to-background and robust Z’ having mean values (± SD) of 3.48 ± 0.42 and 0.72 ± 0.07, respectively. A good correlation was observed between the replicate testing of the compounds with 202 compounds (3% hit rate) found to inhibit more than 60% of the signal in both replicate plates.   

¹ Clatot J. Ginn N. Costain G. Goldberg E. doi: 10.1002/acn3.51707

To enable the study of ion channels found on the lysosomal membrane we perform the lysosomal patch-clamp technique:

• Cells are seeded out at a high density onto Poly-D-Lysine coated coverslips. This ensures that the cells are well adhered to the coverslip, and that they form a vast network, which facilitates easier slicing and extraction of the lysosomes from the cells.
• The cells are treated overnight with a small chemical called vacuolin-1. This chemical helps to enlarge the lysosomes, so they are big enough to be patched with a pipette.
• The following day, the coverslip is incubated in neutral red dye, before it is transferred to the recording chamber of the manual patch rig. The neutral red dye stains acidic components within the cell and enables the visualization of lysosomes which are suitable for extraction and patching.
• The coverslip is then scanned for a lysosome that is larger than the diameter of the pipette tip, and close to the edge of a cell so that it can easily be extracted and patched.
• A relatively sharp pipette is used to slice the cell membrane to create a rupture point through which the lysosome can be squeezed
• A fresh fire polished pipette is then used to patch the lysosome. It is filled with intracellular solution, placed on the pipette holder, put into the solution chamber, and used to approach the lysosome on the coverslip.
• When a gigaseal has been formed on the lysosome, a zap or voltage pulse is used to break in and achieve the whole-lysosome configuration.

See this in action in our video demonstrating the lysosomal patch-clamp technique to study ion channels on the lysosomal membrane.

Find out more about our specialist neuroscience services.

Our webinar ‘In Vitro Assessment of Cardiac Risk in Drug Discovery’ enabled attendees to learn how an hiPSC-CM model can help provide clear decision-making data for their project team, avoiding costly issues related to QTc and QRS cardiac liabilities in the clinic.

Presentations were received from:

Derek Leishman (VP Translational and Quantitative Toxicology at Eli Lilly and Company) presented the opportunities a sponsor now has available to increase the efficiency and effectiveness of QTc assessment by leveraging the ICH S7B core assays. He also discussed times when the already conducted core hERG and in vivo assays do not meet the new expected ‘best practice’, and addressed how gaps in best practice or limitations in tested exposures could be mitigated.

Steve Jenkinson (VP Drug Discovery and Safety at Metrion) described a model utilizing a voltage sensitive dye in combination with a fast capture rate plate reader to generate high quality action potential recordings in a 96 well based format. Moreover, using an extensive and robust reference data set, the translation of key endpoints from this assay allows the prediction of compound plasma exposures in the clinic that will be associated with a 10 ms change in QTc for novel preclinical compounds, as well as provide an insight into the probability of potential QRS liabilities.

Questions from delegates with answers from the presenters are provided below. If you have further questions relating to this webinar, or would like to learn more about how Metrion can support you with preclinical cardiac safety please contact us.

Regarding legacy data, are sponsors currently being held to the new ICH, S7B Q&A standard? What if you have GLP hERG data that was generated using different protocols?

This is a tough one for everyone right now. It’s a situation that we’ve been in before, when IHC E14 was first introduced, we had the situation where we had a lag between the introduction of new guidance and everybody’s assays and clinical studies catching up. We’ve submitted a number of waiver requests based on legacy data. I have to say that we don’t win them all. We’ve had some, regulators have said, yeah, this hERG is fine, even though it wasn’t best practice. We’ve had others that have been more insistent on us doing a new hERG study. In general, if you have a very large margin it’s easier to argue that even if you did have some deviations from what might be best practice, given that you’ve got a large margin, it’s unlikely that the margin would erode. But you also have to have some supporting data with the reference agent. Then you’ve got the other issue that one regulator may say “Yes, I’ll accept your legacy hERG.” but another one doesn’t. So we find ourselves in the situation now of doing repeat hERGs.

If you have a compound for a life-threatening condition, for example in the oncology field where there are no current therapies, and you get a finding in E14 SB – does it still prohibit approval?

Those are situations where the question is “Do you or do you not have a risk?” And then risk benefit is the second question. We have seen that there have been a number of compounds that have been approved with QT prolongation, and if they’ve got QT prolongation, they presumably also had narrow margins in hERG and in vivo and those compounds are approved. Obviously, it depends on the indication and some of those considerations. It will always be a review question, so I don’t think you’ll get an early answer from the regulators because they want to see what the entire package looks like in the end and how good your efficacy is. It’s all very well saying it’s for a life-threatening indication, but it has to work, to really demonstrate the benefit relative to that risk. Overall, it’s a risk benefit situation – you can obviously move forward to some degree of risk.

Does the asset (hiPSC-Cardiomyocyte model) that you just presented
on actually meet the standards outlined in the updated S7B Q&As for
regulatory decision making?

When it was developed, we went through the various sections of the guidance and tried our best to address every single one of them – and I believe we addressed every single one. In the routine running of this assay it doesn’t make sense to do compound concentration verification for every study because you’re usually using this to compare a reasonable number of early compounds. This is an assay I tend to use an earlier stage in assessment not right at the very end. However, if you need to use it as part of a package, then at that stage you can do the compound concentration verification quite easily. The assay is run to the correct standards. We do have the same data that Derek alluded to (the three reference compounds Moxifloxacin, Dofetilide and Ondansetron and all have been shown to be in alignment with the FDA’s data. So, as a package, it’s very tight.

Are hERG GLP studies required for antibody therapeutics and biologics?

Generally regarding antibodies, the answer of no. There’s no requirement for a standalone study for monoclonal antibodies either. But the jury’s out on the other biologics. There’s a draft clinical pharmacology guidance from the FDA on all the nucleotides and on peptides. Both would suggest you have to do some work and treat them essentially as small molecules. You can kind of get a pass if your peptide only has natural amino acids, but my experience is that almost every modern drug peptide has some non-natural amino acid added. So that exception doesn’t really help you too much. Is an open topic though. We will go back now as the ICH S7B 14 group and develop some Q&As around this because lots of people are asking about it. ICH S7B was very much created at a time when most companies portfolios were dominated by small molecules. But actually, if you look at the portfolios of many large companies now, and some small companies focussed on biologics, small molecules have become far rarer than, than they were at the time of ICH S7B finalisation.

In terms of an E14 S7B hERG study, what about positive control?

At Metrion we obviously run these. In my experience having done electrophysiology, nobody wants to run Dofetilide due to its slow kinetics. So probably taken that one off the table. You’ve then got moxifloxacin and Ondansetron and most people’s experience is of Ondansetron being so fast is that it’s actually a pretty reasonable positive control to use. But there’s probably nothing essentially wrong with Moxifloxacin either.
Most CROs are focusing in on Ondansetron just because it’s well behaved. It’s in that sweet spot – not too potent and not too weak. So, yeah, I think Ondansetron is probably going to be the reference compound of choice. Derek is hopefully going to be releasing a publication sometime soon covering the various reference compounds and the data from multiple CROs. It’s important to have all three compounds, as at least in your back pocket, in case that’s required for a regulatory filing.

Regarding translation using IPSC: if you’ve got a compound that’s hitting multiple ion channels does that activity translate? You’ve clearly shown that it does for hERG, but what about compound with mixed ion channel pharmacology?

You’re always limited by the clinical data you’ve got. Using reference compounds is great, but it’s always interesting to see whether, it will continue to translate, for the compounds we’ve seen so far. With regards to specifically multi-ion channel effects (I can’t go into too much detail here, but this will be published sometime soon), a compound a quite potent hERG blocker, and the exposure was going to be right on top of where the hERG block was going to be. You’d expect to see QT in the clinic, but it also had a little bit of weak calcium activity, a little bit like verapamil and its profile. The QT waiver was declined on that once it had to go through to a full TQT study and the stem cell data showed that it wouldn’t have any QT prolongation and it didn’t in TQT study. We’ve got data showing that the assay will pick up defects, but we also have data for this assay showing that it will show a negative when you would expect to see a negative because of that multi-ion channel effect. So that’s reassuring.

What would it take for in vitro hiPSC-CM models to completely replace animal testing? Do you think this is possible or will animal testing not be replaceable?

Although there are several publications out there looking at various aspect of translation with respect to ephys I don’t feel that there is a sufficient number of robust studies looking at the same endpoint to really provide the confidence that we have with say manual hERG patch clamp. In addition, we do know that there are limitations to this system with some proteins not being expressed to the same level as in native tissue. That being said it could be argued that animal models suffer from similar limitations. Moreover, for functional responses (contractility) it is clear that naïve hiPSC-CMs do not generate translatable data without some sort of maturation. There are a wide variety of approaches used in this respect which makes it difficult for regulators to understand the subtleties of each model. This is certainly an area where a more focused approach across the industry would help.

If your compound binds to hERG and another ion channel that is expressed at lower levels in this system versus primary cells will the cardiomyocytes not be as representative as primary cells and be misleading?

The expression of several of the key channels involves in the generation and maintenance of the action potential in hiPSC-CMs is the same as found in human primary cardiomyocytes. However, there are differences in the expression with other channels. For the compounds analysed in our translational study the data from the stem cell is extremely predictive of the clinical effect. However, it is possible that if a compound does interact with a target that is differentially expressed that there may be a difference between the systems.

Considering the “predictivity” of hiPSC cardiomyocytes from Steve’s presentation and the CiPA28 study, why wasn’t hiPSC CMC assays made compulsory along with hERG and in vivo models in the recent Q&As?

My personal feeling is that there has not been enough work done yet. The data from the CiPA28 study only used 4 concentrations so as far as I was concerned there was never enough granularity in the data. Also, the fact that they compared to TdP was always an issue for me. The biomarker used in the clinic is QTc so the studies should have focused on that. I think then there might have been more confidence. Its clear from the recent HESI meeting that the FDA are not currently using the stem cell data for TQT waiver decisions, however I would argue that is because most assays don’t have a really robust translational data set that has been performed in alignment with the S7B guidance. I think this assay does tick those boxes.

For the iPSC-CM predictive QTc model, is there a specific assumed mechanistic context under which it can be used (e.g., you need to know there is hERG inhibition)? For example, was the model validated with NaV1.5 or CaV1.2 channel activators?

From the profile that you get you can make some pretty reliable interpretations of what may be going on in the absence of ion channel data, however having the additional data is always helpful since the assay can also highlight effects that are not necessarily ion channel mediated (including general tox – especially with longer exposures). The assay was validated using compound with hERG, Cav1.2 and/or Nav1.5 activity (in general blockers rather than activators). There was a wide variety of pharmacological profiles used in the initial translational study. Each ion channel or mixed effect has a specific profile that acts like a fingerprint. It’s a really useful assay when you are trying to work out what the consequence of the combination of various activities might be in a clinical setting.

What do you do for risk assessment where compounds that induce complete cessation of beating (i.e., flat BeRST signal)? How is signal amplitude used?

A cessation of beating is obviously a concern in itself and we have seen that this translates pretty week at least into rodent species (from experience). It is what we see at test concentrations just prior to cessation that is important. If you see a large increase in rise time then this suggests to cessation is Nav1.5 dependent. If you see and increase in beat rate prior then that suggests Cav1.2 block. So, the data provide a good idea with regards to a starting point when trying to derisk an adverse finding.

Did you correct the APD changes for the beating rate of the iPSC-CMs?

Yes, we did. We used the Yamamoto correction.

For multi-ion channel blockers, the PR interval and J-Tp interval on the ECG are crucial for assessing the inward current block (i.e., late INa or ICa). However, field potential recordings in iPSC-CMs lack P waves and T waves. How can the effects of a multi-ion channel blocker on field potential be assessed in iPSC-CMs?

We are measuring action potentials, not field potentials, although similarly we are not looking at an ECG response. However, for compounds with multi-ion channel block we do see specific phenotypes and the assay give us a good idea of the main effects. For example, hERG prolongs APD90, Cav1.2 block shortens APD90 but also increases beat rate (a quirk of the stem cell), Nav1.5 shortens rise time. Both Cav1.2 and Nav1.5 will eventually produce quiescence but only after you see the above effects.

Prior to joining Metrion I had the privilege of co-chairing the Secondary Pharmacology Working Group under the auspice of the IQ DruSafe Consortium. This team consisted of a collaborative group of colleagues from across industry including members from Sanofi, GSK, UCB, Novartis, Vertex, Janssen, Takeda, Merck, AbbVie, Roche as well as others.

The team conducted an extensive survey to highlight similarities and differences in screening strategies and target panels across the pharmaceutical industry and as a result we identified a number of opportunities for further optimisation within the secondary pharmacology assessment of novel compounds.

This work has now been published in Nature Reviews in Drug Discovery and highlights:

• A top-level view of the current state of the art in secondary pharmacology screening.
• Best practices, including additional safety-associated targets not covered by most current screening panels.
• Approaches for interpreting and reporting off-target activities.
• Assessment of the safety impact of secondary pharmacology screening.
• Perspective on opportunities and challenges in this rapidly developing field.

Read the full publication: Brennan, R.J., Jenkinson, S., Brown, A. et al. The state of the art in secondary pharmacology and its impact on the safety of new medicines. Nat Rev Drug Discov (2024). https://doi.org/10.1038/s41573-024-00942-3.

Find out about our GLP hERG screening services.