News Archives - Sophion
Safety pharmacology with aging population Sophion paper

Sophion authored paper addresses the challenge of safety pharmacology in the elderly

Despite the looming problems that a growing elderly population causes drug discovery, limited, concrete solutions have been offered to address medicinal developments for the elderly. This threatens to engulf societies across the world.

In a thought-provoking review, ex-Pfizer safety pharmacology expert Bernard Fermini and Sophion scientist Damian Bell have called on the drug discovery community to open discussions and act to develop and implement adequate, robust, and safe testing of medicines for the aging demographic.

We have made the review open access (no paywall), read the paper in full here

Sophion-hiPSC-derived-cell-lines

Latest advances in stem cell recordings on APC reviewed

A Sophion authored pluripotent stem cells and APC review paper shows the much-vaunted use of hiPSC in biomedical research is drawing closer to the promise they hold for safety pharmacology, drug discovery, and personalized medicine.

Sophion read more

Research scientist Kadla Røskva Rosholm, Ph.D., and colleagues at Sophion Bioscience, in conjunction with co-authors Prof. Niels Voigt and scientist Fitzwilliam Seibertz of the University of Göttingen have written a wide-ranging review of techniques and applications of hiPSC, developments driven by high-throughput APC.

Sophion-hiPSC-CM-current-clamp

This figure illustrates paced action potentials in 10 individual hiPSC-cardiomyocyte current clamp recordings from a single measurement QPlate. The expanded action potential shows typical AP characterization measurements: threshold potential (Vt), peak potential (Vp), hyperpolarization potential (Vh), and action potential duration at 90% repolarization (APD90).

View the full, open access paper here

Sophion-hERG-current-traces-22-35C

Successful hERG recordings at 22°C and 35°C on QPatch II

When conducting your ion channel experiments a key environmental factor to consider is temperature. In this latest application report, the conductance, kinetics and pharmacology of the hERG ion channel current, a critical component of the cardiac action potential, were recorded at 22°C and 35°C.

Sophion read more

Like nearly all physiological processes, the activity and pharmacology of ion channels are highly dependent on temperature. Whether making ion channel recordings at mammalian body temperature (~35°C) or simply a consistent room temperature (RT), it is imperative to accurately control the temperature of your recordings. Even ‘simply’ ensuring all your recordings are not subject to the particular vagaries of the lab’s diurnal/seasonal micro-climate can be challenging. With temperature control, by setting the recording site to RT means accurately recording and reporting at 22°C, not the 18-27°C that we all know can be the real world lab RT.

If you want to learn more about temperature control on Sophion’s platforms, read more here

 

Sophion-Webinar-APC-and-hiPSC

Did you miss our second webinar on APC and iPSC from last week?

Research in iPSC holds huge promise for drug discovery. With Sophion’s automated patch technology, we can begin to understand the functional changes taking place in neurons with loss of CDKL5 function.

Last week, guest speaker Elizabeth Buttermore, from Boston Children’s Hospital and Kadla Røskva Rosholm, from Sophion Bioscience presented in collaboration their latest research on cellular, molecular and electrophysiological characterization of CDKL5 deficiency disorder iPSC-derived neurons.

From all over the world, we were happy to see so many engaged and interested participants.

You can see the recorded webinar below:

Sophion-alpha-cobratoxin

Collaborative paper on antibodies neutralizing cobratoxin published by the University of Toronto, Technical University of Denmark and Sophion Bioscience

Snakebite affects some of the poorest populations across the globe and was designated a neglected tropical disease (World Health Organisation, 2017).

In further seminal developments, Sophion has helped to develop and characterize the next generation of monoclonal antibodies to neutralize a key alpha-cobratoxin in the venom of the monocled cobra. The antibodies were discovered and developed via phage display by collaborators at the University of Toronto and the Technical University of Denmark. Their in vitro functional, neutralizing effect on the nicotinic acetyl choline receptor (nAChR) ion channel was determined on QPatch II.

Find the paper published in Protein Science here

Collaborative paper on antibodies neutralizing cobratoxin

Assessment of the in vitro neutralization potency of the top two IgGs was performed via electrophysiological measurements using whole cell patch-clamp. The blockade of ACh-dependent currents by purified α-CTx was reversed by pre-incubation of the toxin with serial dilutions of blocking IgG. Signals were normalized to full response (in the absence of α-CTx and IgG).

New webinar coming up

We now have our next webinar on Automated Patch Clamp and iPSC planned.

In this webinar, Elizabeth Buttermore from Boston Children’s Hospital and Kadla R Rosholm from Sophion will give a joint presentation titled: Cellular, molecular and electrophysiological characterization of CDKL5 deficiency disorder in iPSC-derived neurons.

Drug discovery in neuroscience faces many unique challenges, including access to the central nervous system through the blood-brain barrier and complex biology and circuitry that is still being defined. In order to overcome these challenges to identify treatments for neurodevelopmental disorders, scientists need better preclinical data.

With Sophion’s automated patch technology, we can begin to understand the functional changes taking place in neurons with loss of CDKL5 function. Together, these model systems and technologies can be used to screen for and identify novel therapeutic targets for neurodevelopmental disorders.

 

 

Large Molecules: New application report focus on Wnt signaling pathway activation

In a new application report, written together with Dr. Aamir Ahmed from Kings College London, UK, we obtained automated patch clamp (APC) recordings using the fragile and scarce Wnt proteins. Wnt 9B, 5A and 10B, were all shown to activate ion channel currents in PC3 cells.

Sophion read more

Wingless-related integration site (Wnt) comprises a diverse family of secreted signaling proteins (350–400 amino acids, 35-45 kDa), which act as close-range signaling molecules. Wnt signal activation initiates a complex downstream signal cascade in eukaryotic cells and is critical in the development of many diseases, including cancer.

It was possible to obtain both manual and automated patch clamp recordings of fragile and scarce Wnt proteins after a thorough optimization of the protein handling.

We highlight aspects of the handling of Wnt proteins optimized for APC testing, which could also be applied to other large molecules (e.g. peptide toxins, nanobodies, antibodies).

You can find all relevant Wnt signaling (and other large molecules) publications and posters here

Did you miss last weeks’ webinar “APC and iPSC?

Michael Hendrickson – director of operations at BrainXell presented his data on iPSC-derived human neurons and glia for disease modelling and drug discovery.

After Michaels’s interesting presentation, Daniel Sauter, Science & Engineering Manager at Sophion Bioscience gave a talk titled; Towards more physiological assays: iPSC-derived neurons tested on the 384 channel automated patch clamp platform Qube.

It was great to see a very engaged and inquisitive audience from all parts of the world.

Stay tuned for our next webinar in May.

 

You can see the recorded webinar below:

20 new publications on QPatch or Qube

2021 finished with 20 publications produced on QPatch or Qube.

Labau, et al. (2021). Lacosamide Inhibition of Nav1.7 Channels Depends on its Interaction With the Voltage Sensor Domain and the Channel Pore. Frontiers in Pharmacology, 12(December), 1–17.

Bennett, et al. (2021). Sangivamycin is highly effective against SARS-CoV-2 in vitro and has favorable drug properties. JCI Insight.

Adams et al. (2021). Development of ProTx-II Analogues as Highly Selective Peptide Blockers of Nav 1.7 for the Treatment of Pain. Journal of Medicinal Chemistry.

Grillo et al. (2021). Development of novel multipotent compounds modulating endocannabinoid and dopaminergic systems. European Journal of Medicinal Chemistry, 183.

Tran et al. (2021). Evaluation of Efficient Non-reducing Enzymatic and Chemical Ligation Strategies for Complex Disulfide-Rich Peptides. Bioconjugate Chemistry, 32(11), 2407–2419.

Voronkov et al. (2022). Modifying naloxone to reverse fentanyl-induced overdose. International Journal of Pharmaceutics, 611(November 2021), 121326.

Sang et al. (2021). Synthesis and bioevaluation of diaryl urea derivatives as potential antitumor agents for the treatment of human colorectal cancer. European Journal of Medicinal Chemistry, 229, 114055.

Li et al. (2022). Design, synthesis, and evaluation of potent RIPK1 inhibitors with in vivo anti-inflammatory activity. European Journal of Medicinal Chemistry, 228, 114036.

Zhang et al. (2021). Discovery of quinazolinyl-containing benzamides derivatives as novel HDAC1 inhibitors with in vitro and in vivo antitumor activities. Bioorganic Chemistry, 117(September), 105407.

Wilson et al. (2021). Optimization of TAM16, a Benzofuran That Inhibits the Thioesterase Activity of Pks13; Evaluation toward a Preclinical Candidate for a Novel Antituberculosis Clinical Target. Journal of Medicinal Chemistry.

Kilfoil et al. (2021). Characterization of a high throughput human stem cell cardiomyocyte assay to predict drug-induced changes in clinical electrocardiogram parameters. European Journal of Pharmacology, 912(October), 174584.

Pasquarelli, A. (2021). Proteome and Membrane Channels.

Mori et al. (2022). Corticotropin releasing hormone receptor 2 antagonist, RQ-00490721, for the prevention of pressure overload-induced cardiac dysfunction. Biomedicine & Pharmacotherapy, 146(September 2021), 112566.

Virginio et al. (2021). Identification of positive modulators of TRPM5 channel from a high-throughput screen using a fluorescent membrane potential assay. SLAS Discovery

Di Donato et al. (2021). Therapeutic potential of TRPM8 antagonists in prostate cancer. Scientific Reports, 11(1), 1–16.

Mowbray et al. (2021). DNDI-6148: A Novel Benzoxaborole Preclinical Candidate for the Treatment of Visceral Leishmaniasis. Journal of Medicinal Chemistry, 64(21), 16159–16176.

Schwalen et al. (2021). Scalable Biosynthetic Production of Knotted Peptides Enables ADME and Thermodynamic Folding Studies. ACS Omega, 6(44), 29555–29566.

Dashevsky et al. (2021). Novel Neurotoxic Activity in Calliophis intestinalis Venom. Neurotoxicity Research.

Dongol et al. (2021). Voltage-Gated Sodium Channel Modulation by a New Spider Toxin Ssp1a Isolated From an Australian Theraphosid. Frontiers in Pharmacology, 12(December).

Ballet et al. (2022). In vitro ion channel profile and ex vivo cardiac electrophysiology properties of the R(-) and S(+) enantiomers of hydroxychloroquine. European Journal of Pharmacology, 915(September 2021), 174670.

Enjoy reading, and remember you can always find QPatch and Qube 384 publications on sophion.com in our Publication library.

Sophion-Nanyang-papers

Two papers published by Nanyang Technological University Singapore on QPatch

Profs. Seow Theng Ong, George Chandy and colleagues at A*STAR and Nanyang Technological University, Singapore, have recently published two papers to share their research on ion channels and immunology using our QPatch solution.

In a multi-disciplinary collaboration spanning four continents, they published a Nature Microbiology paper contributing QPatch recordings of KCNJ15/Kir4.2 ion channels in monocyte immune cells. This work furthers our understanding of tuberculosis infection and clearance. The paper can be read here

The second paper generated cryo-EM structures of Kv1.3 ion channels with and without the Kv1.3 toxin peptide analogue dalazatide (ShK-186) bound. Kv1.3 ion channels are a key element in the activation of immune T-cells: by blocking them with dalazatide the over-activity seen in autoimmune diseases (e.g. psoriasis) can be reduced. Find the paper published in PNAS here

Sophion-poster-hIPSC-Göttingen

Big steps in cardiomyocyte action potential recordings on QPatch II

In a fruitful collaboration between Prof. Niels Voigt and scientist Fitzwilliam Seibertz of The University of Göttingen and our research scientist Kadla Røskva Rosholm, PhD, we have made great strides in overcoming the maturation and recording hurdles in the research of human induced pluripotent and stem cell (hiPSCs).

With improved culturing and induction techniques, the Voigt lab have generated consistently ‘matured’ hiPSC-derived CMs. These maturation developments married with significant advances in QPatch II current clamp recordings have led to high quality recordings and success rates.

Action potential recordings were made in physiological Ringer’s solutions on our QPatch II instrument without using fluoride or calcium ‘seal enhancing’ solutions. Our developments on automated patch clamping provides techniques for fast, efficient data generation allowing accurate biophysical and pharmacological characterisation of hiPSC-CMs.

This collaborative data was recently presented at the Biophysical Society meeting. See the poster here

Sophion-travel-and-research-grant

Sophion Travel & Research Grants for students and early career researchers

Sophion are pleased to announce two new grants supporting young scientists: travel & research grants.

We are looking for students (MSc or PhD) or early career scientists (within 5 years of BSc/MSc/PhD award). You are working in ion channels or related fields and you would like to present your work at Sophion’s Ion Channel Modulation Symposium. You could also have QPatch II or Qube384 data and want to tell your story at any international conference. Take this opportunity to make an application for our travel grant.

Alternatively, your postgraduate studies or early career lab research could be rocketed into the stratosphere by applying for our research grant. This will give you access to our platforms and experts in our labs across the world. Sophion’s research grant might be your ticket to completing a key finding for your thesis or strengthening your lab’s latest funding application.

 

For more info & application forms click here.

 

QPatch Compact on display at SLAS, in Boston, USA

QPatch Compact will change the way you obtain high fidelity patch-clamp recordings. You can execute up to eight independent experiments simultaneously. If you are new to patch clamping, you can learn to operate the instrument in less than 30 minutes. If you are more experienced, just plug in the device and take advantage of the robustness of QPatch Compact, no drifting micromanipulator, no electrodes needed to be chloridized, no mechanical fragility, etc. Read more here.

Did you miss our webinar last week?

Large molecules, such as antibodies, venom toxins and peptides, have been increasingly prominent in ion channel research and drug discovery, bringing new ideas and modalities to the field.

To date, small molecule Nav interventions have been largely unsuccessful in the clinic, primarily due to challenges in developing compounds with high subtype selectivity to minimise off-target effects.​ Several toxins are highly potent and specific to individual Nav subtypes, and as such have become widely-used tools in research to elucidate the structure and function of the channels. However, they have not answered all the questions and only a small proportion of animal venoms have been researched.

In this webinar, Steve Trim (Venomtech) and Juha Kammonen (Charles River Laboratories) present a collaboration screening a fractionated venom library in 384-well format on the Sophion Qube high-throughput automated patch clamp platform against Nav1.4 and Nav1.7. Kim Boddum will talk about Sophion’s work on large molecules.

See the webinar here:

QPatch Compact semi-automated patch clamping

Introducing QPatch Compact – semi-automated patch clamping

With QPatch Compact, anyone can learn to patch-clamp in less than half an hour. The ready-to-use system offers the flexibility of manual patch clamp with the robustness and ease of use known from the QPatch and Qube automated patch clamping solutions.

QPatch Compact is a semi-automated patch-clamp solution enabling you to conduct up to 8 experiments at the same time, either synchronized to increase replicates or independent to increase information content in a short time.

The software helps you set up and analyze your experiments. All you must do is prepare the cells and handle the pipetting. QPatch Compact does the rest.

Imagine a benchtop instrument that you simply plug in and conduct your experiments without needing an antivibration table, micromanipulator, faraday cage, etc.

QPatch Compact gives you:

  • Stable recordings
  • Integrated system
  • Small footprint
  • Giga-seal on demand

Read more.

Yale’s Waxman lab publishes first paper on Qube 384

Just over a year after Prof. Stephen Waxman acquired a Qube 384 and QPatch II for his lab at Yale University, the lab has published their first paper using the Qube.

Julie Labau was lead author on a paper that further refined the Nav1.7 binding site and mechanism of lacosamide, an antiepileptic drug that has also been used in the treatment of chronic pain.

This is the first of many publications that will be driven by Sophion’s automated patch clamp platforms coming out of the Waxman lab. In addition to many more publications, rumours are that the Waxman lab is pushing the technology in highly innovative and novel assays and research areas, so watch this space for more news.

Congratulations to Julie Labau, the Waxman lab and collaborators from the Universities of Maastricht and Milan.

See the paper here.

Happy Holidays

Brand new publications published in Q3 using Qube 384 or QPatch

A particularly strong quarter in neglected tropical disease therapeutics was apparent. From foundational work on antibodies neutralising snakebite venom to drug development for malaria, schistosomiasis and cryptosporidiosis were all driven by studies on QPatch.

Our understanding in chronic pain, cancer & respiratory disorders such as asthma & cystic fibrosis was furthered by several academic & industrial labs using Qube & QPatch.

 

Ledsgaard et al., 2021 In vitro discovery and optimization of a human monoclonal antibody that neutralizes neurotoxicity and lethality of cobra snake venom. BioRxiv, 2021.09.07.459075.

Hamilton et al., 2021 Discovery of IACS-9779 and IACS-70465 as Potent Inhibitors Targeting Indoleamine 2,3-Dioxygenase 1 (IDO1) Apoenzyme. Journal of Medicinal Chemistry, 64(15), 11302–11329.

Mambwe et al., 2021 Structure-Activity Relationship Studies Reveal New Astemizole Analogues Active against Plasmodium falciparum in Vitro. ACS Medicinal Chemistry Letters, 12(8), 1333–1341

Hao et al., 2021 Emerging Modulators of TMEM16A and Their Therapeutic Potential. Journal of Membrane Biology, 254(4), 353–365

Roecker et al., 2021 Discovery of Arylsulfonamide Nav1.7 Inhibitors: IVIVC, MPO Methods, and Optimization of Selectivity Profile. ACS Medicinal Chemistry Letters, 12(6), 1038–1049.

Gardner et al., 2021 The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species. PLoS Neglected Tropical Diseases, 15(7), 1–21.

Danziger et al., 2021 Nav1.7 target modulation and efficacy can be measured in nonhuman primate assays. Science Translational Medicine, 13(594), 1–14.

Oboh et al., 2021 Optimization of the Urea Linker of Triazolopyridazine MMV665917 Results in a New Anticryptosporidial Lead with Improved Potency and Predicted hERG Safety Margin. Journal of Medicinal Chemistry, 64(15), 11729–11745.

Shackleford et al., 2021 Discovery and Structure-Activity Relationships of Quinazolinone-2-carboxamide Derivatives as Novel Orally Efficacious Antimalarials. Journal of Medicinal Chemistry, 64(17), 12582–12602.

Feng et al., 2021 N -Aromatic-Substituted Indazole Derivatives as Brain-Penetrant and Orally Bioavailable JNK3 Inhibitors. ACS Medicinal Chemistry Letters, 12(10), 1546–1552.

hIPSC Cardiomyocyte recordings using physiological solutions on QPatch II

hiPSC cardiomyocyte recordings using physiological solutions on QPatch ll

Induced pluripotent stem cell (iPSC) technology has created exciting new opportunities for cardiovascular research by providing a new platform to study the mechanisms of disease pathogenesis and evaluate cardiac drug safety.

It is challenging to get consistent APC recordings on hiPSC cardiomyocytes due to poor cell quality (high batch to batch variation), problematic getting high cell harvest purity, or inconsistent cell maturity.

This AR demonstrates that we can run hiPSC-CM experiments in physiological solutions with up to 50% success rates. Furthermore, we also demonstrate that it is possible to record paced action potentials with up to 20% success rates.

Read the entire report here.

The data was obtained as part of a collaboration with Professor Niels Voigt and his group at University Medical Center Göttingen, Germany.

Society for Neuroscience posters on large molecule drug discovery & stem cell (hiPSC) derived neuron recordings using automated patch clamp

The world’s neuroscientists gather virtually for the annual Society for Neuroscience meeting this week, November 8-11th (with preview days on 3rd – 7th).

We are, as always, present.

Elaine Duncan (CRL and Uni Glasgow) as well as Sophion scientists Drs. Beatrice Badone & Kim Boddum will present the latest developments via virtual poster video walk-throughs at SfN.

Large molecules and APC

Visit poster (01) to see Elaine Duncan and Charles River Laboratories project with Venomtech Ltd. They identified novel and selective sodium channel modulators by screening a fractionated venom library on the Sophion Qube 384. Live poster session is at 14:45 GMT on Tuesday 9th November.

Another virtual poster (05) will be presented by Kim Boddum addressing the potential of recombinant monoclonal antibodies (mAbs) to neutralize snake venom. Live poster session is at 16:00 GMT on 11th November.

Both studies add another piece to the puzzle that shows that automated patch clamp is (also) highly relevant for large molecule drug discovery.

 

Stem cells and APC

If you are interested in stem cell work on APC, please listen in on Beatrice Badone’s virtual poster presentation (P937.01). Beatrice talks about using APC systems QPatch and Qube 384 for studying voltage-gated (NaV, KV) and ligand-gated (GABAA) ion channels by comparing two different brain models: i) primary neurons and astrocytes dissociated from mouse and rat brains, respectively; and ii) hiPSC-derived motor neurons. Live poster session is at 16:00 GMT on Thursday 11th November.

 

Click here to see the live presentations. Please note that you will need to sign up for the meeting to get access to the live presentations.

Leiurus quinquestriatus hebraeus also known as the death stalker. Photo credit: Arie van der Meijden / University of Porto

Large molecules and automated patch clamp: A case study of Scorpion toxin block of BK channels on Qube 384

Currently, more than 90% of approved drugs are small molecules, but large molecules (>1.000 Da, also known as biologics) are rapidly rising in prominence and importance in drug discovery and already constitute the lion’s share of the top 10 selling drugs worldwide. Large molecules have gained attention due to their mode of action, often achieving greater target specificity and potency than small molecule drugs.

While automated patch clamp systems have been used for small molecule drug discovery and characterization for the past 20 years, the use of APC systems for large molecule characterization have been scarcer. However, our systems are fully capable of characterizing large molecules such as peptides, toxins, knotbodies and antibodies.

In this new application report, we show that Qube 384 is fully capable of performing pharmacology measure­ments with large molecules, but also that the low volume microfluidic application ensures that expensive and scarce molecules like antibodies and toxins can be effi­ciently tested.

The effect of ChTx was evaluated on Qube to show affinity in accordance with that found in the literature. Also, the time course of block was concentration-dependent, which could be monitored due to the microfluidic architecture of QChip. The same principle allows for testing of such scarcely available or expensive compounds because the quantity needed is as little as 18 µL per concentration. Read more here.

Leiurus quinquestriatus hebraeus also known as the death stalker. Photo credit: Arie van der Meijden / University of Porto
Leiurus quinquestriatus hebraeus also known as the death stalker.
Photo credit: Arie van der Meijden / University of Porto
QPatch II at Linköping University

Linköping University epilepsy research accelerated by QPatch II

Work that normally takes a year can be completed in approximately a week … it will enable us to open up new territory” – Prof. Fredrik Elinder describing the acceleration in epilepsy research at Linköping University on their newly acquired QPatch II.

In an interview with Linköping University news, Prof. Elinder and Dr Nina Ottosson talked about the new acquisition for their labs. They plan to use the QPatch II to rapidly and efficiently characterize pine resin acid derivatives, aiming to discover and develop improved openers of the huKv7.2/7.3 (M-current) ion channels to treat epilepsy. They also discussed their plans for a shared, core automated patch clamp facility that would be available to support and develop the academic ion channel community across Sweden.

Congratulations from all at Sophion on this QPatch II facility and we look forward to supporting you in all your ion channel endeavours in the future.

You can also see Nina Ottosson discussing their research in a webinar here:

hIPSC Cardiomyocyte recordings using physiological solutions on QPatch II

iPSC cardiomyocyte recordings on QPatch II with success rates of up to 50%

Induced pluripotent stem cell (iPSC) technology has created exciting new opportunities for cardiovascular research by providing a new platform to study the mechanisms of disease pathogenesis and evaluate cardiac drug safety.

For automated patch clamp (APC) assays the potential of human iPSC-derived cardiomyocytes (hiPSC CMs) in drug development, as well as in drug toxicity testing, has been hindered by the lack of robust and reproducible APC assays and broad use of hIPSC CM APC assays is yet to be achieved. However, knowing their critical importance we have worked hard to optimize sample preparation and assays to efficiently work with human hiPSC CMs.

Cav, Nav and hERG currents were recorded, as well as action potentials. In the initial experiments, we obtained up to 50% success rates and went on with more challenging, complex and longer experiments that included pharmacology, which understandably reduced success rates, but provided even more conclusive and useful data.

Below you can take a sneak peek of data examples on Cav1.2 currents and action potential recordings. The data was obtained as part of a collaboration with Professor Niels Voigt and his group at University Medical Center Göttingen, Germany.

APC (QPatch II) studies of Cav1.2 currents in hiPSC-derived cardiomyocytes (hiPSC CMs) in physiological Ringer’s solution

 

Figure 1: APC (QPatch II) studies of Cav1.2 currents in hiPSC-derived cardiomyocytes (hiPSC CMs) in physiological Ringer’s solution. Left: The success rate, in the percentage of 48 experiment sites, of successful experiments (black bar) and of CMs with a voltage-dependent Ca2+ (Cav) current (ICav < -100 pA, grey bar). Error bars are SD of NQPlates = 3. Middle: Representative Ca2+ current traces elicited across a range of voltage steps (from -40 to +60 mV), before (black) and after (red) the addition of 10 µM nifedipine. Right: Cav current density as a function of voltage before (black) and after (red) the addition of 10 µM nifedipine. Data points are AVG ± SD of NCells = 28.

APC (QPatchII) measurements of paced action potentials in hiPSC-derived cardiomyocytes (hiPSC CMs) in physiological Ringer’s solution

Figure 2: APC (QPatchII) measurements of paced action potentials in hiPSC-derived cardiomyocytes (hiPSC CMs) in physiological Ringer’s solution. Top left: The success rate, in percentage of 48 experiment sites, of successful experiments (black bar) and of CMs with paced action potentials (grey bar). Error bars are SD of NQPlates = 2. Top right: Example of spontaneous action potentials recorded in iPSC CMs. Bottom left: Average resting membrane potential (RMP) in CMs with paced action potentials. Error bars are SD of NCells = 7. Bottom middle: Paced action potential before (black) and after (red) addition of 10 µM nifedipine. Bottom right: The action potential duration at 90% (APD90) was calculated and plotted before (black bar) and after (red bar) addition of 10 µM nifedipine. Error bars are SD of NCells = 7.

 

Stay tuned. An application report will follow soon.

 

Sophion, DTU, Universidad Costa Rica & IONTAS collaboration on breakthrough antivenom paper

In a breakthrough in antivenom R&D, an industry-academia collaboration between Sophion, DTU, Universidad de Costa Rica and IONTAS has discovered and developed a monoclonal antibody that neutralizes cobra venom.

Using the QPatch, Sophion’s Kim Boddum showed the neutralizing antibody effect on the venom against its neuronal target, the alpha-7 nicotinic acetylcholine receptor (nAChR).

This work provides another great example of automated patch clamp use in large molecule therapeutic development.

Sophion is particularly proud to have contributed to this work since venoms have devastating impacts in the poorest regions of the world and have been overlooked by pharma. Consequently, in 2017 WHO designated snakebite a neglected tropical disease.

Congratulations to lead authors Line Ledsgaard, Andreas Laustsen, Aneesh Karatt-Vellatt & all authors on this seminal and much-needed research.

Read the paper here.

Sophion PNAS paper on nanomaterials & the blood brain barrier

Whilst Sophion are known for our expertise in ion channel recordings, our scientists are also leading the way in understanding the physiological effects of nanomaterials crossing the blood brain barrier (BBB).

PNAS cover image.
Metallic nanomaterials crossing the blood–brain barrier. Authors found that the shape, size, and intrinsic solubility of various metallic nanomaterials influence their biotransformation, which modulates their transport form, efficiency, and pathways through the blood brain barrier and subsequent neurotoxicity.

Nanomaterials hold great promise for future technologies & applications. But as we enter this brave new nanoworld, so we must determine the safety of these new materials.

Funded by the Marie Curie charity this seminal study was an academic-industry collaboration crossing four countries & two continents, in which Sophion’s head of innovation & technology development Dr. Sandra Wilson was a co-author. The study authors also created the cover image & was published in the prestigious journal Proceedings of the National Academy of Sciences (PNAS).

The study investigated the effects of metallic nanomaterials crossing the BBB, leading to better understanding of these materials in the body & their potential for neurotoxicity in the brain. This invaluable study will allow us to make safer nanomaterials with a range of uses including drug delivery & nanomedicines.

Congratulations to first author Zhiling Guo, Sandra & all authors on this groundbreaking research. You can follow this link to read more.

Ion channel talks for graduate and undergraduate students

Sophion’s Daniel Sauter recently gave a talk on ‘Ion Channel Drug Discovery’ at Universidad De La Salle Bajio, Mexico. The talk was live on Facebook and covered how automated patch clamp plays a key role in discovering new medicines in this critical target class…….. the what, why & how we study ion channels, including a typical drug screening cascade.

Fear not if you missed this excellent talk, the video recording can be found here on Facebook

Thanks to Dr. Miriam Sanchez of the Centro de Neurociencias at Universidad De La Salle Bajio, Mexico, for hosting Daniel & producing & sharing such a professional lecture video.

If you are interested in one of our application scientists give a similar talk on ‘Ion Channels and Automated Patch Clamping’ for your graduate or undergraduate students please contact us (info@sophion.com) or use the contact box on the homepage.

Plant cell electrophysiology on QPatch II

Caroline Ivsic came to our labs as an intern in Ballerup, Copenhagen, with a passion for environmental & green issues. Marrying Caroline’s passion with our passion for ion channels, she recently presented her work developing QPatch II recordings of plant cells alongside fellow students on the course at Sup’Biotech, as reported on LinkedIn.

Plant cells have distinct challenges in making electrophysiological recordings, e.g. removal of the cellulose wall to give the ‘clean’ lipid membrane recording surface of a protoplast. Caroline’s work provides progress towards plant cell ion channel assay development, which in future could be developed into plant ion channel assays to combat plant disease, reduce synthetic fertilizer use, develop environmentally friendly insecticides & improved crop yields.

If you have interest in plant cell ion channel recordings on QPatch or Qube, for further info please feel free to contact us at info@sophion.com

Global academic-industry collaboration developing anti-venom antibodies

The development of snakebite antivenoms has remained largely unchanged for over a century. The tried and tested technique involved inoculating horses with snake venoms: the horse immune response generates antibodies that can neutralize the snake venom. However, these equine derived anti-venoms are time-consuming to make, can have limited efficacy and can cause immune responses in human snakebite patients.

Snakebites cause the most injuries and fatalities in developing countries, affecting some of the poorest regions in the world. A lack of research and therapeutic development led the World Health Organization to designate snakebite as a Neglected Tropical Disease in 2017.

Using the latest antibody engineering techniques and technologies Andreas Laustsen’s Tropical Pharmacology Lab, DTU, Copenhagen has approached this problem with innovative science and solutions in this much needed, but neglected, area of medicine. In a global collaboration across academia and industry with Sophion Biosciences (Denmark), IONTAS (UK) and the Instituto Clodomiro Picado (Costa Rica), they have bio-engineered antibodies to neutralise snake venom toxins.

Line Ledsgaard, a PhD student in the Laustsen lab, DTU, gave a talk on this groundbreaking work.

You can see more talks on the Tropical Pharmacology Lab’s critical anti-venom work here.

New Whitepaper: Automated Patch Clamp in Cystic Fibrosis Drug Discovery

In October 2020, Enterprise Therapeutics’ TMEM16A programme was acquired by Roche/Genentech. This acquisition was the culmination of a research and discovery journey initiated in 2014, with the goal of providing a novel treatment paradigm suitable for patients with cystic fibrosis and other muco-obstructive diseases.

In this new whitepaper, we describe how APC was instrumental in the success of Enterprise Therapeutics’ TMEM16A programme or as Martin Gosling (CEO) describes it “Automated
electrophysiology has been KEY not only in finding the chemistry start points but in supporting the programme through its entire lead optimization”.

Sophion and Genedata announces integration of QPatch II and Qube 384 data to Genedata Screener

We are therefore happy to announce that we, from the forthcoming Genedata Screener release in summer 2021, will be a Genedata ready-to-run partner offering seamless integration to Genedata from the Qube 384 and QPatch II platforms.

Many QPatch or Qube 384 use Genedata for compiling screening data from different platforms into one joint analyzer platform so that APC data can be analyzed in a screening context, i.e., integrated with molecule and assay property information. Also, while Sophion users are confident with Sophion Analyzer, data often needs to be communicated and understood by, e.g. chemists. Genedata is thus also used as a joint company-wide platform for sharing and analyzing data.

Read the press release here and read more about the Genedata solution here.

Two cardiac publications authored by Sophion scientists

Sophion scientists have co-authored two cardiac ion channel publications.

Sophion Japan had a fruitful collaboration with Toho University, Tokyo. Together they published Qube data defining the anti-atrial fibrillatory activity of Oseltamivir. Find the publication in Frontiers in Pharmacology here.

 

Damian Bell worked with Bernard Fermini, one of the Godfathers of ion channels in cardiac safety assessment, writing a comprehensive review on the history, development & future of automated patch clamp in cardiac safety pharmacology. We’d like to thank Dr Fermini for his time, efforts & lending his decades of knowledge & experience. Find their review in the Journal of Pharmacological and Toxicological Methods here (we’ve made it open access, too):

Virtual Ion Channel Modulation Symposium 2021

When life gives you lemons…. organise a virtual meeting. To keep the ICMS-spirit alive we have chosen to have a virtual mini ICMS this year, and you are invited.

Mark your calendar for 16th June from 3:00 PM to 5:00 PM CET

As the symposium is a virtual one, there will unfortunately not be any nice lunch breaks and face-to-face networking with colleagues and friends, no dinner in the Great Hall followed by drinks in the JCR Students’ bar.

But that being said, we are planning next year’s ICMS already, and, this will be a physical symposium as we know it from the past four years. And we can’t wait.  More information about the dates will be communicated during the summer.

 

 

 

 

 

QPatch II 48 at University of Zürich

If you are in the vicinity of the University of Zürich and interested in conducting automated electrophysiology on a brand new QPatch II 48, then you have a great opportunity now. Just contact ephac@mls.uzh.ch at the university. Click here if you’d like to learn more.

 

New software release for Qube and QPatch II

Sophion Analyzer is common for our two platforms Qube and QPatch II and is now being released in new versions. Qube is version Goldcrest, and QPatch ll is version Earth.

The main news is that you can utilise “higher-level results on lower levels”. This feature opens a whole new way of analysing your results with much more powerful and flexible methods of generating baselines and normalisations.

If you are in safety screening, you will appreciate the predefined and FDA recognised CiPA-report format feature – one click is all it takes to report safety data.

Over the years, many people have asked for mean IV curves, so we spent some of the long Covid-19 days in front of the computer to generate that.

Yale University suggested that we make a three-parameter Boltzmann fit to get even more value out of activation and inactivation protocols, and voilà, that is also now available.

We appreciate these many wishes and try to fulfil as many as possible to fortify the position as a one-stop shop for genuine E-phys research and development.

On the experiment execution side, there is also news:

For Qube: voltage protocols can now be commanded in sub-ms steps, and the ligand-exposure time is customisable from 0.8 s and up. This gives even better control over desensitising ligand-gated targets.

For QPatch ll: adaptive protocols (aka V½) have been expanded to Vxx so you can manipulate the channels into precisely the state you find relevant. The individual Vxx can be used both to stimulate and as Vhold. You can follow live traces for the entire liquid period to better see interesting pharmacological effects on the screening station, so it becomes even more thrilling to do the analysis – manually or automatically, as you previously knew it.

There are many more details in Qube Goldcrest and QPatch ll Earth, and your Application Scientist is more than happy to show you these. The upgrades are available now, and as usual, you can both do it yourself, or we can do it for you – just let us know your preference….and if you are not a customer yet, well, then we can also help you solve that, too.

10 toasty-fresh-off-the-press publications were published in Q1 using QPatch or Qube 384.

2021 is off to a flying start with 10 QPatch or Qube 384 publications.

Unsurprisingly, the ion channel community have turned their attention to Covid-19 research. Three papers this quarter (from collaborations between UCB, B’SYS GmbH, Charles River Laboratories, Eli Lilly and Company, Certara, University of Oxford, Eisai, University of Tokyo, Novartis & AnaBios Corporation) studied the cardiac ion channel safety of the anti-malarials chloroquine & hydroxychloroquine, that were proposed as re-purposed Covid-19 medications.

A further 7 publications were evenly split between pharma (Novartis, Orion Pharma, Gedeon Richter, Tsumura & Co.) & academic research (University of Queensland; Flinders University; SAHMRI; University of Pittsburgh; Kyushu Dental University; University of Dundee; Infectious Disease Research Institute, Seattle). They cover a veritable cornucopia of ion channel science: pain, irritable bowel syndrome, tuberculosis, cognitive enhancement & safety pharmacology assessment.

Two selected highlights from this quarter’s publications:

Cardoso et al. & Hasan et al. – not one but two more publications off the red-hot printing press at the University of Queensland. In the first, Cardoso et al. describe tarantula toxin activity on ion channels in chronic visceral pain. The second, Hasan et al. compared transient transfection methods for CaV2.2 & NaV1.7 ion channel expression, using QPatch to define the channels’ biophysics & pharmacology. This excellent methods paper will be presented at our next virtual Sophion User Meeting by Drs. Mahadhi Hasan & Fernanda Cardoso on 6th May. Read more here.

Enjoy this quarter’s reading list and don’t forget: you can always find QPatch and Qube 384 publications on sophion.com in our Publication library

Markert et al., 2021 “Discovery of LYS006, a Potent and Highly Selective Inhibitor of Leukotriene A 4 Hydrolase. Journal of Medicinal Chemistry, 64(4), 1889–1903.

Delaunois et al., 2021 Applying the CiPA Approach to Evaluate Cardiac Proarrhythmia Risk of some Antimalarials Used Off-label in the First Wave of COVID-19. European Journal of Medicinal Chemistry.

Okada et al., 2021 “Chloroquine and hydroxychloroquine provoke arrhythmias at concentrations higher than those clinically used to treat COVID-19. A simulation study”. Clinical and Translational Science.

Hasan et al., 2021 “Transfection methods for high-throughput cellular assays of voltage-gated calcium and sodium channels involved in pain”. PLOS ONE, 16(3), e0243645.

Jordaan et al., 2021 “Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes”. Toxicological Sciences.

Ray et al., 2021 “Spirocycle MmpL3 Inhibitors with Improved hERG and Cytotoxicity Profiles as Inhibitors of Mycobacterium tuberculosis Growth”. ACS Omega.

Borgini et al., 2021 “Chemical modulation of Kv7 potassium channels”. RSC Medicinal Chemistry.

Ledneczki et al., 2021 “Discovery of novel positive allosteric modulators of the α7 nicotinic acetylcholine receptor: Scaffold hopping approach”. European Journal of Medicinal Chemistry, 214, 113189.

Miyamura et al., 2021 “Isoliquiritigenin, an active ingredient of Glycyrrhiza, elicits antinociceptive effects via inhibition of Nav channels”. Naunyn-Schmiedeberg’s Archives of Pharmacology.

Cardoso et al., 2021 “A spider-venom peptide with multitarget activity on sodium and calcium channels alleviate chronic visceral pain in a model of irritable bowel syndrome”. Pain, 162(2), 569–581.

Sophion Virtual User Meeting

We are planning our next virtual Sophion User Meeting so please mark your calendar. The meeting will take place at 12 noon (EDT) and 6 PM (CEST) and will last for around 3 hours with a lineup of around 3-4 speakers.

While we are still working on creating a really interesting program for you, we can already introduce the following speakers:

  • Thomas Binzer, VP R&D and Marketing – Sophion Bioscience
  • Fernanda Caldas Cardoso & Mahadhi Hasan – The University of Queensland
  • Mads P. G. Korsgaard, Global Product Manager for Qube – Sophion Bioscience
  • Manuel Paina – Axxam
  • Muthukrishnan Renganathan – Eurofins

If you are prevented from attending we will record the meeting for you to watch at a later time.

 

 

 

 

 

We reserve the right to turn down any registrant.

7 new peer-reviewed papers & 2 methods book chapters QPatch or Qube 384 in Q4

9 new publications were published in Q4 using QPatch or Qube 384.

Two book chapters in the Springer-Nature published methods book ‘Patch Clamp Electrophysiology’ (co-edited by Drs. Mark Dallas & Damian Bell) were written by Sophion scientists, one on Qube perforated patch-clamp, the other on optogenetics using the Opto Qube 384. These chapters add to the growing methods & capabilities available on the Qube.

The remaining 7 were a nice mix of pharma (ESTEVE, Taisho, Quentis Therapeutics, Orion Pharma), a CRO-academic collaboration (NMI-TT/University of Konstanz) & academia (University of Queensland, University of Texas). They also cover a broad range of ion channel science: pain, cancer, gram negative bacterial infectious diseases, cardiac safety, neurotoxicity & venoms.

One exotic highlight came out from a collaboration between the Vetter, Craik & Durek labs at the University of Queensland (Gilding et al., Sci.Adv., 2020), who provide yet another very thorough investigation of the weird & wonderful Australian venomous species. Whilst you’re probably aware of the venomous fauna (snakes, scorpions, spiders, fish-hunting cone snails) even the flora Down Under can be venomous: here they fractionate, chemically define, preform behavioural studies & electrophysiologically determine activity against the Nav1.7 ion channel of the venom of Australian stinging tree. A single sting from this tree can be excruciatingly painful & may last for weeks, even months, as reported in Nature’s Research Highlights.

Boddum, K., Skafte-Pedersen, P., Rolland, J. F., & Wilson, S. (2021). Optogenetics and Optical Tools in Automated Patch Clamping. In Methods in Molecular Biology.

Rosholm, K. R., Boddum, K., & Lindquist, A. (2021). Perforated Whole-Cell Recordings in Automated Patch Clamp Electrophysiology. In Methods in Molecular Biology.

Díaz, J. L., García, M., Torrens, A., Caamaño, A. M., Enjo, J., Sicre, C., Lorente, A., Port, A., Montero, A., Yeste, S., Álvarez, I., Martín, M., Maldonado, R., de laPuente, B., Vidal-Torres, A., Cendán, C. M., Vela, J. M., & Almansa, C. (2020). EST64454: a Highly Soluble σ 1 Receptor Antagonist Clinical Candidate for Pain Management.

Loser, D., Schaefer, J., Danker, T., Möller, C., Brüll, M., Suciu, I., Ückert, A. K., Klima, S., Leist, M., & Kraushaar, U. (2020). Human neuronal signaling and communication assays to assess functional neurotoxicity.

Gilding, E. K., Jami, S., Deuis, J. R., Israel, M. R., Harvey, P. J., Poth, A. G., Rehm, F. B. H., Stow, J. L., Robinson, S. D., Yap, K., Brown, D. L., Hamilton, B. R., Andersson, D., Craik, D. J., Vetter, I., & Durek, T. (2020). Neurotoxic peptides from the venom of the giant Australian stinging tree.

Otsomaa, L., Levijoki, J., Wohlfahrt, G., Chapman, H., Koivisto, A. P., Syrjänen, K., Koskelainen, T., Peltokorpi, S. E., Finckenberg, P., Heikkilä, A., Abi-Gerges, N., Ghetti, A., Miller, P. E., Page, G., Mervaala, E., Nagy, N., Kohajda, Z., Jost, N., Virág, L., … Papp, J. G. (2020). Discovery and characterization of ORM-11372, a novel inhibitor of the sodium-calcium exchanger with positive inotropic activity.

García, M., Virgili, M., Alonso, M., Alegret, C., Farran, J., Fernández, B., Bordas, M., Pascual, R., Burgueño, J., Vidal-Torres, A., Fernández De Henestrosa, A. R., Ayet, E., Merlos, M., Vela, J. M., Plata-Salamán, C. R., & Almansa, C. (2020). Discovery of EST73502, a Dual μ-Opioid Receptor Agonist and σ1Receptor Antagonist Clinical Candidate for the Treatment of Pain.

Soth, M. J., Le, K., Di Francesco, M. E., Hamilton, M. M., Liu, G., Burke, J. P., Carroll, C. L., Kovacs, J. J., Bardenhagen, J. P., Bristow, C. A., Cardozo, M., Czako, B., De Stanchina, E., Feng, N., Garvey, J. R., Gay, J. P., Do, M. K. G., Greer, J., Han, M., … Jones, P. (2020). Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties.

Ushiyama, F., Takashima, H., Matsuda, Y., Ogata, Y., Sasamoto, N., Kurimoto-Tsuruta, R., Ueki, K., Tanaka-Yamamoto, N., Endo, M., Mima, M., Fujita, K., Takata, I., Tsuji, S., Yamashita, H., Okumura, H., Otake, K., & Sugiyama, H. (2021). Lead optimization of 2-hydroxymethyl imidazoles as non-hydroxamate LpxC inhibitors: Discovery of TP0586532.

 

 

iPSC-derived cortical neurons characterized with Qube 384

With the high throughput and recording fidelity of Qube, it was possible to characterize the ion channel populations in iPSC-derived cortical neurons. 60-70% of cells expressed Nav-current and 60-80% expressed Kv-current. Biophysical as well as pharmacological tools were employed to characterize these currents and the phenotypes were compared between a CDKL5 Deficiency Disorder and isogenic control. Click here to see the poster.

Visit our lab from the comfort of your home

We are excited to invite you to our 3D virtual lab.

In this lab, you don’t need hand sanitizer, lab coat or face mask. You can wear your oldest trainers or sit on your sofa while casually strolling through the lab, and for once a cup of coffee can be brought along.

Have a walk through our lab – we are excited to hear how you like it

Visit the Sophion Virtual Showroom



High Throughput Screening on Kv1.5 using Qube 384 Mk II

The Kv1.5 channel is found in many tissues and is the molecular background behind Ikur in the heart – contributing to the heart’s repolarisation. If it does not work well, you can die. However, blocking this channel pharmacologically might treat various heart arrhythmias so, therefore, it can be beneficial to screen for that, so we have developed an HTS assay for this target. Read more here.

Drug Discovery for Ion Channels XXII – virtual satellite Meeting

Sophion Bioscience are happy again to co-sponsor the annual satellite meeting: Drug Discovery for Ion Channels but this year in a virtual version.

Together with the other organisers Metrion Biosciences, Fluxion, SB Drug Discovery and Nanion, we look forward to bidding you welcome.

We have an exciting speaker line up including Irina Vetter from the University of Queensland, Andrew Jenkins – Emory University, Julie Klint – Lundbeck, John Atack – Cardiff University, Steven Griffin – University of Leeds, David Baez-Nieto – Broad Institute of MIT and Harvard.

 

QPatch ll 48 installed at ApconiX

ApconiX, the integrated toxicology and ion channel company, has acquired a QPatch ll 48 with temperature control to meet the increasing demand from their clients. As the first CRO to invest in QPatch II in the UK, this instrument allows the ApconiX team to continue to deliver top-quality ion channel services for their existing and new clients and to further deliver on their exceptional data quality and rapid turnaround time.

The QPatch ll system was selected for its unique possibility to achieve gigaohm seals in physiological solutions, without the use of seal enhancers and for its ability to control the temperature at the measurement sites. The instrument was installed at the beginning of November and the installation went smoothly. The ApconiX team were able to handle assay setup, execution of experiments and results analysis within the week of installation and training.

Director and Co-founder of ApconiX, Michael Morton, explains:

“We know Sophion Bioscience from collaborations in the past and we have used QPatch with great success, so it was an obvious choice to start up the partnership again to meet the increased demand. Of course, our clients demand high-quality data, and many have specific requests such as running assays in physiological solutions and better temperature control during runs. QPatch ll was the obvious choice for us since it meets all these demands and more. QPatch II has some great updates and new features, and the new design is stunning. Most significantly, it’s great to be part of the Sophion family again and I look forward to future collaborations with them.

 

ApconiX are experts in ion channel biology, target safety assessments and in all aspects of nonclinical programme design and delivery.

ApconiX was formed by three AstraZeneca colleagues with the drive and ambition to create a world-renowned company founded on the skills and experience of a growing team with a wide range of expertise in nonclinical drug safety.

The model for the pharmaceutical industry has evolved in recent years with large pharma reducing internal capability and outsourcing key skills to trusted partners.  There are many more SMEs and academic groups who also need access to specialised services. https://www.apconix.com/

 

Twelve new peer-reviewed publications using QPatch or Qube 384 in Q3

̶T̶w̶e̶l̶v̶e̶ thirteen new peer-reviewed publications were published in Q3 using QPatch or Qube 384.

Most of the publications this quarter came from the pharma industry, with publications from Gedeon Richter, Eisai, Lundbeck, Sanofi, Novartis, Esteve, Taisho Pharmaceuticals. However, as always, a few from academia with one from University of Heidelberg using Qube 384 and also, as always, a massive input from the University of Queensland with four publications. To our knowledge that brings the University of Queensland up to 12 publications using QPatch in 2020 alone.

NMDA, Cav3.X, the full sodium channel panel Nav1-8 and the entire CiPA safety panel have been investigated. Also, a few of the QPatch publications were only used for hERG safety testing. While this might be of less scientific relevance it is great to see that the QPatch still are the benchmark for cardiac safety testing and hERG counter screens.

Topics are diverse, from NMDA research to early drug discovery and lead optimisation.

Of the more exotic topics, we could highlight Wang er al 2020 and McMahon et al. 2020 using QPatch to characterise the effect of conotoxins, a group of neurotoxic peptides isolated from the venom of the predatory marine cone snails of the genus Conus.

Le Marois et al. 2020 might be a good evening read. This group at Sanofi in Paris, France, has evaluated the effect of the non-psychoactive component of Cannabis (CBD) on seven major cardiac currents. They show that CBD impacts cardiac electrophysiology, so hold back on the cannabis oil if you have heart problems.

Enjoy the read, and remember you can always find QPatch and Qube 384 publications on sophion.com in our publication library

Bozó et al. 2020. “New V1a Receptor Antagonist. Part 2. Identification and Optimization of Triazolobenzazepines.” Bioorganic & Medicinal Chemistry Letters 30(18): 127417.

Fukushima et al. 2020. “Inhibitory Effect of Anti-Seizure Medications on Ionotropic Glutamate Receptors: Special Focus on AMPA Receptor Subunits.” Epilepsy Research 167: 106452.

Grupe et al. 2020. “In Vitro and in Vivo Characterization of Lu AA41178: A Novel, Brain Penetrant, Pan-Selective Kv7 Potassium Channel Opener with Efficacy in Preclinical Models of Epileptic Seizures and Psychiatric Disorders.” European Journal of Pharmacology: 173440.

Le Marois et al. 2020. “Cannabidiol Inhibits Multiple Cardiac Ion Channels and Shortens Ventricular Action Potential Duration in Vitro.” European Journal of Pharmacology 886: 173542.

McMahon et al. 2020. “Discovery, Pharmacological Characterisation and NMR Structure of the Novel µ-Conotoxin SxIIIC, a Potent and Irreversible NaV Channel Inhibitor.” Biomedicines 8(10): 391.

Sharma et al. 2020. “Recombinant Production, Bioconjugation and Membrane Binding Studies of Pn3a , a Selective Na V 1 . 7 Inhibitor.” Biochemical Pharmacology: 114148.

Skepper et al. 2020. “Topoisomerase Inhibitors Addressing Fluoroquinolone Resistance in Gram-Negative Bacteria.” Journal of Medicinal Chemistry.

Wang et al. 2020. “Characterisation of δ -Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator.” Marine Drugs 7: 1–13

Peschel et al. 2020. “Two for the Price of One: Heterobivalent Ligand Design Targeting Two Binding Sites on Voltage-Gated Sodium Channels Slows Ligand Dissociation and Enhances Potency.” Journal of Medicinal Chemistry: acs.jmedchem.0c01107

García et al. 2020. “Discovery of EST73502, a Dual μ-Opioid Receptor Agonist and σ 1 Receptor Antagonist Clinical Candidate for the Treatment of Pain.” Journal of Medicinal Chemistry 52862.

Ushiyama et al. 2020. “Lead Optimization of 8-(Methylamino)-2-Oxo-1,2-Dihydroquinolines as Bacterial Type II Topoisomerase Inhibitors.” Bioorganic and Medicinal Chemistry 28(22): 115776.

Merz et al. 2020. “A Microscopy-Based Small Molecule Screen in Primary Neurons Reveals Neuroprotective Properties of the FDA-Approved Anti-Viral Drug Elvitegravir.” Molecular Brain 13(1): 1–14.

Cardoso et al., 2020. “A spider-venom peptide with multitarget activity on sodium and calcium channels alleviates chronic visceral pain in a model of irritable bowel syndrome.” Pain: doi: 10.1097/j.pain.0000000000002041

First ever QPatch ll installation in South Korea

Sophion and SureMedical have successfully installed the first QPatch ll at SK Biopharma in South Korea. SureMedical worked closely with the new user to find the right APC solution for their needs and we are happy to say they decided on a QPatch ll system with temperature control. This solution is a perfect fit for them regarding throughput, obtaining true Giga-ohm seals in physiological solutions and being able to control the temperature accurately at the measurement sites.

Despite these Covid-19 times, installation and training went according to plan and the new users are up and running. We are sure that SK Biopharma will put their new QPatch ll to good use and continue to break new ground in drug discovery.

QPlate, a unique design enabling high performance automated patch clamp

The unique design of our QPlates provides many advantages. Among others 100% liquid exchange, giga-seals in physiological solutions and no need for electrode maintenance.

In this application report, we tell about the design and advantages of using microflow-based consumables for Automated Patch Clamp.

Learn how the QPlate materials make it possible to create giga-ohm seals with physiological solutions. See data demonstrating that 100% solution exchange can be achieved with 20 µL of solution.

Learn about the QPlate design and its performance here.

Webinar: Automated Patch Clamp in Academia

Sophion Bioscience invites you to our very first webinar

In these Corona times, we are pleased to be still able to organise scientific meetings although in a different manner than we’re used to. Join us for an online meeting on APC in academia on

Thursday 3rd December at 4:00 PM (CET)

 

For this webinar, we are pleased to introduce Dr Damian Bell from Sophion Bioscience. Damian will present Sophions’ work with Bridging the Gap Between Basic & Applied Research.

Damian will be followed by Dr Nina Ottosson from Linköping University who will give a talk about  APC in Academia – Screening of Resin Acid Derivatives as Kv7.2/7.3 channel openers

In these Corona times, we are pleased to be still able to organise scientific meetings although in a different manner than we’re used to. Join us for a webinar on Automated Patch Clamp in academia on Thursday 3rd December at 4:00 PM (CET).

Click here to register.

 

We reserve the right to turn down any registrant.

New book on Ion Channel Electrophysiology Methods

The book aims to provide hands-on methods, practical advice & tips & tricks rarely captured in typical methods sections. It’s written for both neophyte and experienced researchers alike, providing foundational and latest, cutting edge techniques to add to their armoury of ion channel recording techniques.

This collection of methods and protocols was written by leading researchers in the field, generously sharing their knowledge and experience to further our collective understanding of ion channels.

Two of the chapters were written by experts at Sophion:

Kadla Røskva Rosholm, Kim Boddum and Anders Lindqvist wrote ‘Perforated Whole-Cell Recordings in Automated Patch Clamp Electrophysiology’; whilst

Kim Boddum, Peder Skafte-Pedersen, Jean-Francois Rolland (Axxam Spa.) and Sandra Wilson wrote a chapter entitled ‘Optogenetics and Optical Tools in Automated Patch Clamping’.

Link to the book can be found here.

Upcoming Networking Event hosted by BPS: A World of Opportunity: Ion Channels and Automated Patch-Clamping

We invite you to attend the Biophysical Society’s event: A World of Opportunity: Ion Channels and Automated Patch-Clamping.”

Hear from accomplished speakers with experience working in pharma, academia, and biotechnology cover topics, including why they chose a career working with ion channels, the transition from academia to industry, profound discoveries as a result of their work, and where they see the field moving towards in the future.

 

HTS on Kv1.5 n Qube 384 Mk II

The Kv1.5 channel is found in many tissues and is the molecular background behind Ikur in the heart – contributing to the repolarization of the heart. If it does not work well, you can die. However, blocking this channel pharmacologically might treat various heart arrhythmias so therefore it can be beneficial to screen for that, so we have developed an HTS assay for this target. Read the report here.

VP R&D and Marketing at Sophion, Thomas Binzer, on automated patch clamp, marketing in science and building bridges with academia

If you are curious to know more about Sophions’ APC robots and their use in industry and academia, please read Artem Kondratskyis’ interview with our ur VP R&D and MKTG, Thomas Binzer which can be found online on the ionchannellibrary.com.

An interview about automated patch clamp, academic collaborations and why we are using all those Qs in our names.

Cell density of Qube and QPatch ll

Sophion generally recommends having a cell density of 3×106 cells/mL on both Qube and QPatch ll, but our newest data demonstrates that the cell consumption can be reduced significantly and still ensure success rates above 90%. This data provides user benefits such as costs and time savings. However, we recommend that optimal cell concentrations are evaluated for each individual cell line and especially when working with cells that are expensive or in short supply. Read the whole application report here.

Eurofins Panlabs Inc. announces the upgrade to 384-format Automated Patch-Clamping

In July, Eurofins acquired a Qube 384, which was installed shortly after. As always, the selection process was lengthy and thorough to ensure that Eurofins selected the instrument that provided the best voltage clamp, success rates and unattended usage. After careful consideration, the group selected the Sophion Bioscience Qube 384. The instrument installation went smoothly, and the staff was able to handle the setup and execution of experiments after just one week of installation and training.

The Scientific Director at Eurofins, Bryan Koci, explains:

“We made a thorough comparison in the field of 384-APC’s and selected Qube 384 for its high performance and design, where everything is integrated and user-friendly. Being in the midst of unusual times because of the global impact of Covid-19, at Eurofins, our primary concern is our commitments to deliver to our clients and the safety of our employees and their families. We believe an extra benefit of the Qube 384 platform is that it can run mostly unattended, without significant intervention from the staff, allowing a safer work environment for our employees while continuing to provide uninterrupted services for clients. The Qube384 platform is an exciting addition to Eurofins Discovery’s comprehensive ion channel screening services and we are looking forward to providing high-quality, high throughput, screening data on Qube 384 to our clients in the near future.”

Cav1.2 ready to use cells without rundown

Get your experiments up and running in a matter of few minutes – and maintain the current level for endless minutes, even if the target is the notorious run-down prone Cav1.2. Indeed very convenient to work with these cells provided by NMI TT Pharmaservices. Pharmacology behaves as expected and you can even look for subtle, holding-potential-dependent, differences in state-dependent mode of action. See the whole application report here.

Damian Bell will start at Sophion as Director of Scientific Affairs

Many of you probably already know Damian. He has a long track record within the field of ion channels. He has more than 25 years’ experience from world-leading academic, pharmaceutical, biotechnology and CRO labs. Damian’s’ work has been focused on channel drug discovery across a broad range of therapeutic areas including chronic pain, respiratory, autoimmunity and neurological disorders.

At Sophion, we have known Damian, almost from the beginning of time, and we are excited that he is now (finally) a part of the team.

Damian has extensive experience with Automated Patch Clamp (APC), and has worked on pretty much all APC platforms since the beginning of the ‘APC-era’. However, he has never actually used a Qube 384, so we are looking forward to the introduction course. But again, he has never driven a Ferrari either.

Damian will start with us on October 1st. He will have his base in the UK, but will have frequent visits to Copenhagen, Boston and other Sophion sites, and will off course also be a frequent traveller to meet customers and partners across the world. That, of course, if the COVID-19 situation improves and travel restrictions will ease up.

Virtual User Meeting hosted by Sophion NA

We had a fantastic slate of speakers representing a variety of different industries each presenting their experiences with automated patch clamping. These presentations were followed by a live demo of the QPatch II 48 Automated Patch-Clamp Instrument with a focus on the Temperature Control features. A big thank you to Application Scientist Melanie Schupp and Product Manager Mads Korsgaard for staying late in Ballerup in order to run the demo.

The meeting was well attended with over 50 external participants representing 27 separate institutions. We were thrilled to see attendees from all over the globe, with many calling in from Europe and even Japan.

Thanks also go to all of our speakers who did a fantastic job presenting their research in an engaging way in this new virtual environment, Daniel who did an excellent job of running the program, Schuyler who set up the WebEx platform and managed the production, and Daniel, Sung, and Weifeng for recruiting such a good group of speakers both from the industry as well as academia.

​​​The one thing we will need to work on for our next virtual User Meeting is to figure out how we can get the participants a round of Lord Hobo beer for the annual User Meeting beer tasting event!

If you take a picture of the QR code below you will have the opportunity to open it and see the agenda and the speaker bios.

Yale School of Medicine and Veterans Administration Acquire Automated Patch-Clamp

The ‘Center for Neuroscience and Regeneration Research’ at Yale School of Medicine and Veterans Affairs West Haven Medical Center has evaluated multiple Automated Patch Clamp (APC) solutions on the market in order to support and enhance their research, predominantly focused on chronic pain. We are happy to announce that the Waxman lab has acquired both Qube 384 and QPatch II 48 robotic patch clamp systems, making Yale and Veterans Affairs West Haven Medical Center one of the few academic institutions to house this powerful new technology.

The choice of both Qube and QPatch II was driven by a desire to both run larger screens and to run more focused assays in physiological solutions. Qube can run larger screens with the ability to run unattended overnight operation and the QPatch family of systems provides the only available medium-throughput APC instruments that can achieve gigaohm seals without the use of seal enhancers. Each of these robotic devices provide high throughput screening capability equivalent to that of half a dozen human electrophysiologists.

A core group of electrophysiologists including Dr. Mark Estacion, Dr. Brian Tanaka and Dr. Sulayman Dib-Hajj, as well as multiple postdoctoral fellows and Yale MD-PhD students, will carry out initial studies using this high throughput instrumentation.

About Center for Neuroscience and Regeneration Research at Yale School of Medicine and Veterans Administration. The goal of the Center for Neuroscience and Regeneration research is to harness the “molecular revolution” in order to restore function in the injured nervous system and to promote functional recovery following spinal cord injury, multiple sclerosis, stroke, traumatic brain injury and neuropathic pain. Read more here

About Director Stephen Waxman MD, PhD, (Bridget M. Flaherty Professor of Neurology and of Neuroscience) founded the Center for Neuroscience and Regeneration Research in 1988 at the Veterans Administration campus in West Haven, Connecticut. He served as the Chairman of Neurology at Yale from 1986 until 2009. Dr. Waxman’s research uses molecular, genetic, biophysical, stem-cell based and pharmacological techniques, together with sophisticated molecular imaging and computer simulations, to study the molecular basis for neurological diseases, especially spinal cord injury, multiple sclerosis, and neuropathic pain, and to search for new treatments that will alleviate suffering in these disorders. Dr. Waxman has published more than 700 scientific papers and his papers have been cited more than 40,000 times. Dr. Waxman has served on the editorial boards of many journals and has trained more than 200 academic neurologists and neuroscientists who lead research teams around the world.  Read more about Dr. Waxman here

Qube Falcon is ready to increase your lab efficiency

Qube Falcon has been released and with that a range of upgrades to continue help finding better drugs faster. Since Eagle, Qube has had adaptive protocols which enables cell-specific recording to obtain much tighter data. Now the adaptive protocols have been more now flexible to cover the whole range from 10-90 % activation/inactivation. The cell-specific result can also be applied to both recording segments and to holding potentials.

Falcon can run idle sweep. These are the sweeps between one compound period and the next and gives more homogenous stimulation frequency of the cells and consequently compound effects.

Qube has sophisticated mechanisms to compensate for series resistance, capacitance and leak and with Falcon, we have faster computers to calculate all these parameters in parallel for all 384 amplifiers in only a little more than 4 seconds. Previously it took almost 10 seconds. The improvement means you can e.g. run CiPA hERG protocols with parameter estimation between every sweep.

Qube is a high fidelity automated patch clamp instrument meant to run unattended, for example during the night, and therefore it can also automatically match the barcodes/compound lists your screen and add results and analyzed them automatically in projects.

Don’t hesitate to contact us for more information and both virtual and real-life demonstrations where you get to run the instrument yourself after just a few hours of introduction – that is namely all it takes to safely and error-free handling of an instrument from Sophion.

21 new peer-reviewed publications in Q2

Read about TMEM16A and cystic fibrosis, drug-induced QT prolongation, NaV1.1 activators for epilepsy and many more. Among these, we have two Sophion-authored publications.

Enjoy!

  • Al-Sabi, Ahmed et Al. 2020. “Development of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves.” Bioorganic Chemistry 100(July 2019): 103918.
  • Chow, Chun Yuen et Al. 2020. “A Selective NaV1.1 Activator with Potential for Treatment of Dravet Syndrome Epilepsy.” Biochemical Pharmacology (February): 113991.
  • Diness, Jonas Goldin et Al. 2020. “Inhibition of KCa2 Channels Decreased the Risk of Ventricular Arrhythmia in the Guinea Pig Heart During Induced Hypokalemia.” Frontiers in Pharmacology 11(May): 1–10.
  • Gonzales, Junior et Al. 2020. “Fluorescence Labeling of a NaV1.7-Targeted Peptide for near-Infrared Nerve Visualization.” EJNMMI Research 10(1): 49.
  • Henckels, Kathryn A. et Al. 2020“Development of a QPatch-Automated Electrophysiology Assay for Identifying TMEM16A Small-Molecule Inhibitors.” ASSAY and Drug Development Technologies 18(3): 134–47.
  • Hirsch, Rolf et al. 2020. “Antimicrobial Peptides from Rat-Tailed Maggots of the Drone Fly Eristalis Tenax Show Potent Activity against Multidrug-Resistant Gram-Negative Bacteria.” Microorganisms 8(5): 626.
  • Israel, Mathilde R et Al. 2020. “Characterization of Synthetic Tf2 as a NaV1.3 Selective Pharmacological Probe.” Biomedicines 8(6 Special Issue “Animal Venoms–Curse or Cure?”).
  • Koshman, Yevgeniya E. et al. 2020. “Drug-Induced QT Prolongation: Concordance of Preclinical Anesthetized Canine Model in Relation to Published Clinical Observations for Ten CiPA Drugs.” Journal of Pharmacological and Toxicological Methods 103(February): 106871.
  • Kuramoto, Kazuyuki et al. 2020. “Novel Indirect AMP-Activated Protein Kinase Activators: Identification of a Second-Generation Clinical Candidate with Improved Physicochemical Properties and Reduced HERG Inhibitory Activity.” Chemical and Pharmaceutical Bulletin 68(5): 452–65.
  • Lacivita, Enza et al. 2020. “Privileged Scaffold-Based Design to Identify a Novel Drug-like 5-HT7 Receptor-Preferring Agonist to Target Fragile X Syndrome.” European Journal of Medicinal Chemistry 199: 112395.
  • Liao, Weike et al. 2020. “Design, Synthesis and Biological Activity of Novel 2,3,4,5-Tetra-Substituted Thiophene Derivatives as PI3Kα Inhibitors with Potent Antitumor Activity.” European Journal of Medicinal Chemistry 197: 112309.
  • McGivern, Joseph G., and Mei Ding. 2020. “Ion Channels and Relevant Drug Screening Approaches.” SLAS DISCOVERY: Advancing the Science of Drug Discovery 25(5): 413–19.
  • McMahon, Kirsten L. et al. 2020. “Pharmacological Activity and NMR Solution Structure of the Leech Peptide HSTX-I.” Biochemical Pharmacology: 114082.
  • Okumu, Antony et al. 2020. “Novel Bacterial Topoisomerase Inhibitors Derived from Isomannide.” European Journal of Medicinal Chemistry 199: 112324.
  • Ong, Seow Theng et al. 2020. “Modulation of Lymphocyte Potassium Channel Kv3 by Membrane-Penetrating, Joint-Targeting Immunomodulatory Plant Defensin.” ACS Pharmacology & Translational Science: acsptsci.0c00035.
  • Qian, Binbin, Sung-Hoon Park, and Weifeng Yu. 2020. “Screening Assay Protocols Targeting the Nav1.7 Channel Using Qube High-Throughput Automated Patch-Clamp System.” Current Protocols in Pharmacology 89(1): e74.
  • Rozenfeld, Paula A, and Daniel Liedtke. 2020. “Research Article A Big Molecule Induces Schwann Cells in the Peripheral Nervous System Leading to Myelin Sheath Repair.” International journal of Diabetes & Endocrinology Research: 1–13.
  • Schupp, Melanie, Sung-Hoon Park, Binbin Qian, and Weifeng Yu. 2020. “Electrophysiological Studies of GABAA Receptors Using QPatch II, the Next Generation of Automated Patch-Clamp Instruments.” Current Protocols in Pharmacology 89(1): e75.
  • Tran, Hue N T et al. 2020. “Enzymatic Ligation of a Pore Blocker Toxin and a Gating Modifier Toxin: Creating Double-Knotted Peptides with Improved Sodium Channel NaV1.7 Inhibition.” Bioconjugate Chemistry 31(1): 64–73.
  • Walsh, Kenneth B. 2020. “Screening Technologies for Inward Rectifier Potassium Channels: Discovery of New Blockers and Activators.” SLAS DISCOVERY: Advancing the Science of Drug Discovery 25(5): 420–33.
  • Zhu, Fang et al. 2020. “Structural Optimization of Aminopyrimidine-Based CXCR4 Antagonists.” European Journal of Medicinal Chemistry 187: 111914.

Another 20th anniversary

Everybody knows Jørgen Due, and everyone knows that he’s been with Sophion for what seems like a lifetime. More exact 20 years today. Join us in celebrating Jørgen.

Jørgen, just a lad back in 2000, was one of the very first employees, who started working for Sophion. With a genuine pioneer spirit, Jørgen took an active part in building the organisation and can surely take credit for partaking in making Sophion what it is today. Jørgen started as a one-person army being the sole technical support engineer which meant him being on the road most of the time servicing QPatches all over the world. A lot of flight bonus points must have been earned during those years.

While our installed base grew Jørgen has managed, developed and expanded the Technical Support group, and today we have a dedicated and skilled team who helps our partners and clients all over the world.

Jørgen and his team. They may look like bouncers but they are actually very nice lads all of them….

 

Apart from being an excellent technician, Jørgen has always been the go-to person and with his pragmatic and calm demeanour and attitude always willing to lend an ear if you need advice.

Thank you for being such a good colleague and for enduring the first 20 years with Sophion.

We look forward to 20 more.

User Meeting (virtual) – hosted by Sophion NA

The event will be from 11:00 am to 3:30 pm on the 22nd of September, 2020.

Click here for instructions on how to access the Webinar

The agenda will be as follows:

11:00: Sophion Latest News – Mads Korsgaard, Global Product Manager, Sophion Bioscience

11:30: Jonathan Mann, Group Leader Biology Discovery, Charles River Laboratories

12:00: Alexander Komarov, Senior Research Investigator, Knopp Biosciences

12:30: Dang Dao, Research Director, Astellas Institute of Regenerative Medicine

01:00: Mark Estacion, Research Scientist, Yale University

01:30: Sam Goodchild, Senior Research Scientist, Xenon Pharmaceuticals

02:00: Jim Ellis, Chief Scientific Officer, Nocion Therapeutics

02:30: QPatch II with Temperature Control Demonstration – Sung Hoon Park, Application Scientist, Sophion Bioscience

The titles of the presentations will be announced shortly.

The meeting will be held as a webinar and if you want to join, please send an email to Schuyler King.

We are looking forward to having a successful virtual user meeting.

We are staffing up in North America

Daniel Sauter, previous Sophion laboratory manager in Boston, have relocated to California where he will support the western part of USA and Canada. We will be looking for a new application scientist in Boston.

With an increase in installs and activities the last years, it was time to again get some people on the ground on the west coast. We are happy that Daniel has accepted to relocate to San Diego with his wife and two kids. In his new position Daniel will continue to support our users scientifically with his vast knowledge on electrophysiology and expertise on QPatch and Qube 384. Also, Daniel will take on new responsibilities within business development and sales. Over the next month when Daniel gets settled, he will contact users in the area, but you are welcome to take contact to him, if you have questions or just want to welcome him to the golden state (DRS@sophion.com)

Daniel will surely be missed in Boston. We aim to cover Daniels vacancy as soon as possible. Job posting can be found here. It will be big shoes to fill after Daniel, but we are sure that there are still many talented and passionate electrophysiologists out there, so let us know.

20 new publications in Q2 2020

20 peer-reviewed publications have been published in Q2-2020 using Sophion QPatch or Qube 384. Read more about, among others, TMEM16 A and cystic fibrosis, drug-induced QT prolongation, NaV1.1 activators for epilepsy or antimicrobial peptides from a good broad variety of our users from among others Amgen, AbbVie, Acesion Pharma, Astellas Pharma, Evotec, Nanyang Technological University, and also five new publications from the University of Queensland and two Sophion authored publications.

Al-Sabi et Al. 2020. “Development of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves.” Bioorganic Chemistry 100(July 2019): 103918.

Chow et Al. 2020. “A Selective NaV1.1 Activator with Potential for Treatment of Dravet Syndrome Epilepsy.” Biochemical Pharmacology (February): 113991.

Diness et Al. 2020. “Inhibition of KCa2 Channels Decreased the Risk of Ventricular Arrhythmia in the Guinea Pig Heart During Induced Hypokalemia.” Frontiers in Pharmacology 11(May): 1–10.

Gonzales et Al. 2020. “Fluorescence Labeling of a NaV1.7-Targeted Peptide for near-Infrared Nerve Visualization.” EJNMMI Research 10(1): 49.

Henckels et Al. 2020. “Development of a QPatch-Automated Electrophysiology Assay for Identifying TMEM16A Small-Molecule Inhibitors.” ASSAY and Drug Development Technologies 18(3): 134–47.

Hirsch et Al. 2020. “Antimicrobial Peptides from Rat-Tailed Maggots of the Drone Fly Eristalis Tenax Show Potent Activity against Multidrug-Resistant Gram-Negative Bacteria.” Microorganisms 8(5): 626.

Israel et Al. 2020. “Characterization of Synthetic Tf2 as a NaV1.3 Selective Pharmacological Probe.” Biomedicines 8(6 Special Issue “Animal Venoms–Curse or Cure?”).

Koshman et Al. 2020. “Drug-Induced QT Prolongation: Concordance of Preclinical Anesthetized Canine Model in Relation to Published Clinical Observations for Ten CiPA Drugs.” Journal of Pharmacological and Toxicological Methods 103(February): 106871.

Kuramoto et Al. 2020. “Novel Indirect AMP-Activated Protein Kinase Activators: Identification of a Second-Generation Clinical Candidate with Improved Physicochemical Properties and Reduced HERG Inhibitory Activity.” Chemical and Pharmaceutical Bulletin 68(5): 452–65.

Lacivita et Al. 2020. “Privileged Scaffold-Based Design to Identify a Novel Drug-like 5-HT7 Receptor-Preferring Agonist to Target Fragile X Syndrome.” European Journal of Medicinal Chemistry 199: 112395.

Liao et Al. 2020. “Design, Synthesis and Biological Activity of Novel 2,3,4,5-Tetra-Substituted Thiophene Derivatives as PI3Kα Inhibitors with Potent Antitumor Activity.” European Journal of Medicinal Chemistry 197: 112309.

McGivern et Al. 2020. “Ion Channels and Relevant Drug Screening Approaches.” SLAS DISCOVERY: Advancing the Science of Drug Discovery 25(5): 413–19.

McMahon et Al. 2020. “Pharmacological Activity and NMR Solution Structure of the Leech Peptide HSTX-I.” Biochemical Pharmacology: 114082.

Okumu et Al. 2020. “Novel Bacterial Topoisomerase Inhibitors Derived from Isomannide.” European Journal of Medicinal Chemistry 199: 112324.

Ong et Al. 2020. “Modulation of Lymphocyte Potassium Channel Kv1.3 by Membrane-Penetrating, Joint-Targeting Immunomodulatory Plant Defensin.” ACS Pharmacology & Translational Science: acsptsci.0c00035.

Qian et Al. 2020. “Screening Assay Protocols Targeting the Nav1.7 Channel Using Qube High-Throughput Automated Patch-Clamp System.” Current Protocols in Pharmacology 89(1): e74.

Rozenfeld et Al. 2020. “A Big Molecule Induces Schwann Cells in the Peripheral Nervous System Leading to Myelin Sheath Repair.” International journal of Diabetes & Endocrinology Research: 1–13.

Schupp et Al. 2020. “Electrophysiological Studies of GABAA Receptors Using QPatch II, the Next Generation of Automated Patch-Clamp Instruments.” Current Protocols in Pharmacology 89(1): e75.

Walsh 2020. “Screening Technologies for Inward Rectifier Potassium Channels: Discovery of New Blockers and Activators.” SLAS DISCOVERY: Advancing the Science of Drug Discovery 25(5): 420–33.

Zhu et Al. 2020. “Structural Optimization of Aminopyrimidine-Based CXCR4 Antagonists.” European Journal of Medicinal Chemistry 187: 111914.

 

From teenager to early adulthood

From the servers and the drawers, we can still find documentation from the founding years. Here pictures from the founding reception and pictures and drawings of the barracks behind NeuroSearch A/S that was the Sophion ‘home’ for the first year… as well as, ideas, visit reports and visions from 2000 and 2001.

On 5th July 2000, Sophion Bioscience was founded as a spin-off from the Danish pharmaceutical company NeuroSearch. It is hard to believe that 20 years have passed.

From the annals on our servers and a carefully written diary by Sophion’s first CEO Torsten Freltoft, it is fascinating to follow the first years after the founding. As with all start-ups chasing capital was a part of everyday life to secure the development of what ended up being QPatch. Also, longer entries about Fussball-tournaments and fun nights out at conferences take up a lot of space and of course the inauguration of the new facilities that were opened in 2001.

 

From “QPatch Vision” in 2004: Already in 2004 Sophion focused on strong, professional customer support and saw the support as an integrated part of the product offering. Today, more than 15 years later, we continue to drive the business with this customer focus, maintaining a large organization of Application Scientists and Field Service Engineers to support our customers.

With the launch of the QPatch in 2005, Sophion started manufacturing, and focus changed from securing capital for development to securing global growth. Around that time someone wrote in one of those vision statements, that were very popular in the ’00s, that potential users of the APC systems not only needed the system and measurement plates but that strong support from application scientists and field service engineers was needed by users and lacking from other vendors. Today, 16 years later we operate from the same principles, ensuring that our users are always supported by a dedicated team of Application Scientists and Field Service Engineers.

In the years from 2005-2010 new installs were booming and Sophion was on the list of fastest-growing companies in Denmark for four consecutive years. While production was busy ensuring supply for new users, R&D continued new developments on the QPatch introducing, among others, the worlds-first automated Rs compensation, ligand applications, QPatch HT (48), multi-hole QPlates and current clamp. All features that are now standard on all Sophion products and most commercially available platforms.

In 2011 a major transformation occurred when Sophion was integrated with Biolin Scientific. Although ‘only’ 11 years old at that point it forced Sophion to grow-up quickly as a company and we still benefit today from the professionalism and structure that was introduced in the Biolin years. A more efficient supply chain and financial reporting system, as well as our ISO 9001 certification, are all processes that we enjoy today and that made us better equipped for the future.

When Qube 384 was introduced in 2014 it changed the way ion channel drug discovery could be done. With 384 individual channels, patch-clamp experiments running primary screening could suddenly be performed. With the introduction of the stacker solution in 2015, it became possible to perform overnight unattended screens of up to 15 QChips, something which is performed routinely by leading CROs and pharma companies on Qube 384 today.

However, the integration into a larger corporation was not a commercial success, and in 2017 a management buyout resulted in Sophion again being “masters in our own house”. After that, things have speeded up again, as many of our current and new partners have noticed. With the introduction of QPatch II 48, QPatch II 16, Qube Opto, online V½ estimation, and the new improved temperature controller, our APC systems are now easier than ever to use, with more advanced features. Double-digit growth, year on year, for the past 4 years has put us in an interesting new situation where we are running more EU projects, more industry partnerships, and more academic collaborations than ever.

In 2020 Sophion Bioscience is stronger than ever, and despite a challenging “Corona-quarter” in Q2-2020”, the future looks bright and promising. While parts of the world are still in lockdown, the crates shipped from Copenhagen in the past few weeks are a sure sign that other parts of the world are opening up again.

With Qube and QPatch installs in all major pharmaceutical companies we are proud to have left our mark on the ion channel field for the past 20 years and plan to continue doing just that for the next 20 years as well.

“Good habits formed at youth make all the difference”     

Aristotle

We do not know what the future holds. In the first twenty years, we have managed not only to bring the world’s best APC platforms to market, combining high performance and data quality with a design that makes them so easy to use that patch clamping is accessible to everybody. We promised back then to “take the voodoo out of patch clamping”, and we believe we have achieved just that.

What we can promise you for the future; We will continue to be inquisitive and innovative. We will continue to push the boundaries, enabling ion channel drug discovery and adjacent fields by combining ease-of-use with performance. We will do that while honouring the vision from 2004 because we ‘choose to focus on customer support’.

Peer-reviewed papers from Q1 2020

Learn more about TRPV1, NaV1.7, variation between automated patch clamp platforms or TMEM16 and Cystic Fibrosis. See below papers from academic and pharma researchers, among others the CiPA consortium, AbbVie, Genentech, University of Queensland, Enterprise Therapeutics and many more.

Papers

Agwa, A. J. et Al. Manipulation of a spider peptide toxin alters its affinity for lipid bilayers and potency and selectivity for voltage-gated sodium channel subtype 1.7. J. Biol. Chem. 295, 5067–5080 (2020).

Choi, R. et Al. Bumped Kinase Inhibitors as therapy for apicomplexan parasitic diseases: lessons learned. Int. J. Parasitol. (2020) doi:https://doi.org/10.1016/j.ijpara.2020.01.006.

Damann, N. et Al. In vitro characterization of the thermoneutral transient receptor potential vanilloid-1 (TRPV1) inhibitor GRTE16523. Eur. J. Pharmacol. 871, 172934 (2020).

Danahay, H. L. et Al. TMEM16A Potentiation: A Novel Therapeutic Approach for the Treatment of Cystic Fibrosis. Am. J. Respir. Crit. Care Med. 201, 946–954 (2020).

Jalily, P. H. et Al. Put a cork in it: Plugging the M2 viral ion channel to sink influenza. Antiviral Res. 178, 104780 (2020).

Katavolos, P. et Al. Preclinical Safety Assessment of a Highly Selective and Potent Dual Small-Molecule Inhibitor of CBP/P300 in Rats and Dogs. Toxicol. Pathol. 48, 465–480 (2020).

Kramer, J. et Al. Cross-site and cross-platform variability of automated patch clamp assessments of drug effects on human cardiac currents in recombinant cells. Sci. Rep. 10, 1–15 (2020).

Mueller, A. et Al. Mapping the Molecular Surface of the Analgesic Na V 1.7-Selective Peptide Pn3a Reveals Residues Essential for Membrane and Channel Interactions. ACS Pharmacol. Transl. Sci. (2020) doi:10.1021/acsptsci.0c00002.

Ridder et Al. (2020) “A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm”, Toxicology and Applied Pharmacology, Volume 395, 15 May 2020

 

ICMS2021- we miss you!

This week, the 5th Ion Channel Modulation Symposium was supposed to take place in Cambridge, in the United Kingdom, but like many other events around the world, we, unfortunately, had to cancel due to the COVID-19 crisis. All the speakers were in place, the program was ready to be printed and everyone attending from Sophion was looking forward to being there. What a disappointment! We will surely miss you this year.

Take a walk down memory lane – see the photos from the previous symposia below:

  

        

 

 

Sophion – Empowering innovation in drug discovery

An increasing number of patents using QPatch data are published worldwide. More than 350 patent families have been published with the support of QPatch high-quality electrophysiology data since 2005. Last year alone 60 patent families were published supported with QPatch data and the rate of patents filed per year is increasing.

The majority of the patents are filed in the US (46%), with Japan and the UK as follow-ups (11% each) and Switzerland in close pursuit (10%). The remaining 22% comes from a variety of countries with China as the prominent with 5% of the patent filings and then Germany, Italy, Denmark, Sweden etc.
Not surprisingly the majority of patent applications come from big pharma like Shionogi, Dainippon, Novartis, AstraZeneca, J&J and Gilead, but surprisingly, many smaller pharmaceutical companies use the QPatch data as a part of their patent filing.

 

We are of course happy that QPatch is used actively, not only for drug discovery, compound characterization and cardiac safety studies, but are also that QPatch data is used in the patent filings worldwide.

Source: https://worldwide.espacenet.com/

Activate intracellular mechanism with light

With Qube in opto-configuration you can combine optical stimulation with ligand-, voltage- and current-clamp recordings that Qube is already known for. It is a very strong combination which enables short exposure times and unique combinations of stimuli to investigate many interesting aspects of ion channel behaviour with the usual high success rates. Please read more here about the general technique and for stimulation of intracellular process using bPAC.

Contact us for more information.

Cav1.2 on QPatch with no rundown

CaV1.2 is widely expressed in the smooth muscle, pancreatic cells, fibroblasts, and neurons. However, it is particularly important and well known for its expression in the heart where it mediates L-type currents, which causes calcium-induced calcium release. It depolarizes at -30mV and is key in defining the shape of the action potential in cardiac and smooth muscle. It is, therefore, a key ion channel for accessing cardiac safety in drug discovery and one of the key channels investigated as a part of the HESI/FDA supported CiPA studies.

When testing compounds on CaV1.2 on the QPatch, we regularly achieve success rates of >85%, however rundown can be high in some CaV1.2 assays, something that makes it inherently difficult. We tested a new CaV1.2 cell line from Charles River Laboratories with very good results. Using this new cell line on the QPatch, you can look forward to rundown rates as low as -1.2% ± 0.6% per minute (n=43), resulting in trustworthy and reliable pharmacology.

You can read more about CaV1.2 assay on Qube 384 and QPatch here.

If you have issues with rundown in your CaV1.2 assay or would like more information and data about this particular cell line contact our application scientists Melanie Schupp.

ICMS in Cambridge is cancelled

It hardly comes as a surprise that we, due to the severe situation caused by the COVID-19 pandemic, have to cancel the 5th edition of the ICMS, which was scheduled to take place on June 17th and 18th, 2020.

We, at Sophion, are very disappointed to have to cancel the meeting, but we have chosen to follow the current recommendations from the official UK government site.

While we acknowledge that the cancellation will cause great disappointment to every one of you, we fully intend to hold the event again in 2021 and have reserved the venue for the 2nd and 3rd June 2021.

We look forward to seeing everyone in 2021.

Adaptive voltage protocols ensure precise half inactivation application of voltage-gated ion channels

Here we used online adaptive protocols to measure V½ in each individual cell on both QPatch ll and Qube. We showed that individual V½ reduces data variability compared to traditional standard methods and that commercialized drugs with state-dependent effects were successfully detected by V½ stimulation protocol. Please click here to see the poster.

 

Step-by-step protocols for sophisticated, yet easy, screening on Qube

This article describes the basic procedure for setting up the screening protocol and recording data for Nav1.7 on a Qube automated patch‐clamp system. Three protocols along with step‐by‐step details are provided. First, we describe a protocol to estimate V½, the voltage at which half of the channels are inactivated, using traditional steady‐state inactivation measurement as well as a new adaptive online estimation. Second, we establish a state‐dependent protocol using adaptive online V½ measurement to obtain a concentration-response curve (CRC) on known reference blockers. Last, we introduce a use‐dependent protocol. In our hands, the sample reference demonstrated good state‐ and use‐dependent inhibition of Nav1.7.

Click here to see the article

Remote support during the COVID-19 pandemic

Due to the current, global situation, the need for remote training and support is larger than ever. For your convenience, we have therefore listed the tools we use for remote assistance to ensure your instruments and research keeps running.

Online video tutorials:

On the Sophion Academy pages, you can find our online tutorial videos. We are continuously expanding this section, so let us know if you have suggestions for topics. Just send us an email.

Teamviewer access:

For troubleshooting, we can access and diagnose your system online by using TeamViewer. You can download TeamViewer on our Technical Support page. Talk to your Field Service Engineer or Application Scientist about remote access to your system.

Video calls:

Both for technical issues and application support a video call can be a helpful tool. This way you can walk us through an issue and support can be given immediately. We use most available platforms, MS Teams, Skype for Business, Zoom, Whereby or others.

Debug files:

If problems arise debug files are a key tool to diagnose your QPatch or Qube 384. Learn how to download a debug file here or contact your Application Scientist or Field Service Engineer.

E-mails and phone:

As always you can reach out to your Application Scientist of Field Service Engineer

Other:

Inspiration for troubleshooting assays can also be found through Application Reports, peer-reviewed publications, posters and from videos of scientific talks that can be found on the Sophion Knowledge Center.

Stay safe. We are here to help.

First CiPA Paper is published in Nature Scientific Reports

We are happy to see results from the first large CIPA study that has been published in Nature Scientific Reports. The study was co-authored by Sophions own Anders Lindqvist, but lots of credit should also go to the rest of the team.

  • Kramer et Al. (2020) “Cross-site and cross-platform variability of automated patch clamp assessments of drug effects on human cardiac currents in recombinant cells”, Nature Scientific Reports volume 10, Article number: 5627

Results from this large multi-site study provide estimates of the variability associated with IC50 values characterizing the blocking potency of 12 drugs on 4 prominent human cardiac currents using suggested experimental protocols across five automated patch platforms and 17 sites.

QPatch results were provided by ourselves and three independent QPatch users (4 in all) and while platforms are anonymized in the paper we can still say that results confirmed what we already knew.

For the record QPatch data was only run at room temperature. With the newly launched temperature control module for QPatch II that enables accurate control of temperature within a range from 10-42°C with a precision of ±0.5°C, we look forward to running more cardiac assays at elevated temperatures. Read more about the QPatch II temperature control solution here.

Also, the original instructions from the Food and Drug Administration (FDA) did not recommend the use of fluoride in the solutions. For most assays on Sophion ‘Qube 384’ we use fluoride to increase the seal resistance, and since it was not recommended, Qube was omitted from this study. We have now learned that others have used fluoride/seal enhancers during this study and agreed with FDA to include Qube in future CiPA studies. We look forward to that since many laboratories already are using Qube for cardiac liability testing.

For questions please contact Sr. Application Scientist Anders Lindqvist

COVID-19 and Sophion

COVID-19 Update

The escalating outbreak of COVID-19 has affected each one of us in multiple ways, our families, friends, businesses and way of life. This fast-changing situation has forced us, to re-evaluate how we operate at Sophion Bioscience and adapt to the new situation.

We are actively working on using this challenge as an opportunity to make our company more dedicated, more efficient, and more focused on supporting the needs of our users, and an even better company to partner with in the future.

Putting safety first

Our priority is the safety of our staff, our users and our suppliers we frequently interact with. To limit exposure, we have limited international travel and asked our staff to work remotely when possible. We have a good IT infrastructure, and a well-proportioned bandwidth and VPN capacity that allows us to work remotely on even our very large patch-clamp data sets. Also, we have increased our online meeting activities, internally and with customers around the world, so to date, this transition has gone smoothly.

Assembly line per 30 March 2020. Plenty of activity with five Qube 384s and five QPIIs in the making. Production and assembly are running a morning and evening shift, to reduce the risk of infection while maintaining efficiency, so we can meet the demands.

Maintaining production, service and support

Sophion Bioscience laboratories in Copenhagen, Boston, and Tokyo are still operational. However, we have scheduled laboratory hours, so not everyone is at work at the same time to reduce the risk of infection. While laboratory work is key to support our users in assay and application development, reporting and support can easily be done from home offices.

Field Service support is still running; however, scheduled maintenance visits might be postponed and in general, we try to avoid travelling unless for critical repairs. Support is, when possible, done by remote assistance using either TeamViewer access, video calls or regular phone calls. We will, of course, comply with national restrictions, so there are regions where we cannot currently visit.

Production and assembly lines are working, but again, to reduce the risk of infection we are working two shifts. A morning shift and an evening shift.

Minimizing disruption

In the last months, we have seen that many of our users have been de-densifying or closing laboratories. While some users are beginning to scale up again, other users are just beginning the close-down.

We are doing everything in our power to ensure science and innovation do not stop. We still have day-to-day delivery on QPlates and QChips and are planning to ensure deliveries. Production of QPlates and QChips continues uninterrupted, as well as the production of QPatch IIs and Qube 384s.

A few of our users have postponed the install of new systems because of travel restrictions. We will be ready when the world opens up again.

Looking ahead

In these most unusual circumstances, Sophion is renewing our commitment to becoming a better partner to you at the service of the greater cause we all work for, to ‘develop better and safer drugs, faster’. We will continue to be here to help you accomplish this objective during and after this crisis is over.

Please do not hesitate to call on us for any reason. We wish you and everyone around you the best of health and look forward to meeting and engaging with you and your teams in-person soon.

We are positive that we will all come out of this as with a stronger team, a fitter company and hopefully also a more caring world.

QPatch ll Temperature Control

Laboratory temperatures can change from winter to summer or during the day and affect the reproducibility and repeatability of your assay results. With QPatch II temperature control you can ensure that assays are always performed at a constant and controlled temperature (between 10-42°C) with high accuracy (+/-0.5°C).

Consider the temperature control add-on module if you want to:

  • keep a constant controlled temperature to increase repeatability
  • perform assays at physiological temperatures 35-37°C
  • Log assay temperature for GLP and tracking purposes

The new QPatch ll temperature control and regulate temperature at the Bed-of-Nails directly beneath the measurement sites and also the manifold is thermostated to ensure rapid equilibration.

The recorded temperature data is transferred automatically to the analyzer software where further analysis can be made.

Click here to read more about design, accuracy, precision and validation work. Click here to visit the product page.

Status from Sophion

In Denmark, kindergartens have closed, as well as most of the public sector, but special circumstances take special measures.

Thursday we decided that most of our colleagues should work from home as per government recommendation. We still keep the production wheels rolling and make sure that you get your deliveries of systems and consumables on time.

Field Service will continue as usual, although planned maintenance in high-risk areas might be postponed until the situation is improved. We will evaluate the urgency of each visit before booking plane tickets. A videoconference or TeamViewer session can sometimes solve the issue, so that will be the first step in the coming period.

If you have questions or issues you need help with, please don’t hesitate to contact your application scientist or our technical support people or simply drop us a mail.

Don’t miss the next Sophion User Academy in Copenhagen

Do you want to get the latest tips and tricks on your Qube or QPatch?

 

Our next Sophion User Academy will take place on 22nd April at our premises in Copenhagen. Later this year we will also have the Sophion User Academy in both the United States and in Japan this Autumn so stay posted.

Contact your Application Scientist or send us an email if you want to learn more. We are here to help you. We can also help with arranging accommodation during your stay in Copenhagen.

New papers, posters and reports from Q1 2019

See the latest list of publications from Q4 2019.

Learn more about how automated patch clamp can be used in personalized medicine, about ion channels in cancer or about our new feature ‘Adaptive Protocols’. See below papers from academic and pharma researchers, among others Aptuit, Icagen, Charles River, BeiGene, Chugai Pharmaceutical, UC Davis, Nanyang University, University of Queensland and many more

Papers

Ashmore et Al., 2019 Wnts control membrane potential in mammalian cancer cells. The Journal of Physiology, Volume 597, Issue24

Ong et Al., 2019. Extracellular K+ Dampens T Cell Functions: Implications for Immune Suppression in the Tumor Microenvironment. Bioelectricity Vol. 1, No. 3.

Grillo et Al., 2019. Development of novel multipotent compounds modulating endocannabinoid and dopaminergic systems. European Journal of Medicinal Chemistry. Volume 183, 1 December.

Wu et Al., 2019. Synthesis and Biological Evaluation of Five‐Atom‐Linker‐Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile. ChemMedChem 2019, 14, 2042–2051.

Billakota et Al.,  2019. Personalized medicine: Vinpocetine to reverse effects of GABRB3 mutation. Epilepsia 2019;60:2459–2465.

Zhu et Al.,  2019. Structural optimization of aminopyrimidine-based CXCR4 antagonists. European Journal of Medicinal Chemistry, Volume 187, 1 February 2020, 111914

Chow et Al., 2019. Venom Peptides with Dual Modulatory Activity on the Voltage-Gated Sodium Channel NaV1.1 Provide Novel Leads for Development of Antiepileptic Drugs. Pharmacol. Transl. Sci. 2019.

Hue et Al., 2019Enzymatic Ligation of a Pore Blocker Toxin and a Gating Modifier Toxin: Creating Double-Knotted Peptides with Improved Sodium Channel NaV1.7 Inhibition. Bioconjugate Chem. 2020, 31, 1, 64-73

Liu, Li and Chen 2019. Role of High-Throughput Electrophysiology in Drug Discovery. Current Protocols in Pharmacology, 87, e69. doi: 10.1002/cpph.69. REVIEW.

Isobe et Al., 2019. Cardiac safety assessment with motion field imaging analysis of human iPS cell-derived cardiomyocytes is improved by an integrated evaluation with cardiac ion channel profiling. J Toxicol Sci. 2019;44(12):859-870

Werner et Al. 2019. Discovery and Characterization of the Potent and Selective P2X4 Inhibitor N-[4-(3-Chlorophenoxy)-3-sulfamoylphenyl]-2-phenylacetamide (BAY-1797) and Structure-Guided Amelioration of Its CYP3A4 Induction Profile. J. Med. Chem. 2019, 62, 24, 11194-11217

 
Posters

Braksator et Al., 2019Validation of B’SYS KV3.x cell lines using automated and manual patch-clamp electrophysiology. Ion Channel Modulation Symposium, Boston MA, 2019
 
Application Reports

Schupp 2019. Stable Vhalf values and reliable potentiation of Kv7.3/7.2 currents on Qube 384
 
Rosholm 2019Electrophysiological characterization of human iPSC-derived motor neurons using Qube 384 and QPatch

Adaptive protocols at work

Charles River has presented how Qube with adaptive protocols gets tighter data on their Nav1.x panel when testing state-dependent sodium channel blockers. The performance was as good as with standard protocols but with 384 individual protocols, the modulatory effects of local anaesthetics were detected more reliably. Please click here to see the poster.

Annual Meeting of the Biophysical Society 2020

We look forward to seeing at BPS in San Diego in February and again this year there are a lot of activities going on:

 

Friday, 14 February

08:00 AM – 05.00 PM – the annual satellite meeting: Drug Discovery for Ion Channels XX 

 

Monday, 17 February

Poster presentation:

Title: Effectiveness of the Qube in studying the rapidly-desensitizing alpha7 nicotinic acetylcholine receptor 

Presented by application scientist Sung H. Park

Time: 1:45 PM

Poster No.: B488

 

Tuesday, 18 February

09.30 AM – 11.00 AM. A mini-symposium titled:

Characterization of the rapidly desensitizing α7 nicotinic acetylcholine receptor on the Qube, NaV1.1 assays on automated electrophysiology platforms and developing NMDA assays on the Qube system

We have the following speakers presenting at this meeting:

  • Dr Sung Hoon Park, Field Application Scientist, Sophion Bioscience, USA
  • Dr Shanti Amagasu, Senior Scientist, Amgen, USA
  • Dr Juha Kammonen, Group Leader & Scientist, Charles River Laboratories, UK

Venue: Room 33A, San Diego Conference Center

Stable Kv7.2/7.3 current on Qube

The heteromer Kv7.2/7.3 underlying the M-current was recorded in Qube. With high success rates, we saw stable V½ values during multiple recordings and liquid additions. Together with reliable pharmacology using retigabine we have established a high throughput assay on this target, suitable to pick up e.g. new generation antiepileptic drugs. Read more here and feel free to contact us for more information.

Posters from SPS2019 in Barcelona now live

As always we spend some good days at the SPS meeting, getting new acquaintances and meeting old friends and partners.

Steve Jenkinson (Pfizer, San Diego) did a well-received talk:

The use of High-Throughput Multi Ion Channel profiling [on Qube 384 ed.] and in silico modelling in assessing arrhythmia risk: One Pharma’s experience and perspective”.

A very interesting presentation that addressed the Pfizer’s approach to early de-risking in cardiac safety. However, as an oral presentation, we cannot post it here, but watch out for similar talks in the future.

Five posters using QPatch was presented, emphasizing QPatch as the benchmark automated patch clamp solution for cardiac safety

“Electrophysiological characterization of human dopaminergic neurons derived from LUHMES cells”, Udo Kraushaar, Dominik Loser, Timm Danker, Clemens Möller, Marcel Leist. NMI (LINK)

“Functional Assessment of hNav1.x Ion Channels Using State- Dependent Protocols on the QPatch HT Automated Patch Clamp System”, Bryan Koci, Jennifer Wesley, Muthukrishnan Renganathan, Haiyang Wei, Diane Werth, Eurofins (LINK)

“Predicting Cardiac Proarrhythmic Risk Exclusively Using Automated Patch Clamp Data”, Edward SA Humphries, John Ridley, Robert Kirby and Marc Rogers, Metrion Biosciences, UK (LINK)

“Automatic estimation of hNaV1.5 channel inactivation improves pharmacological evaluation using the new adaptive protocol feature on Qube”, Anders Lindqvist, Sophion Biosciences (LINK)

“Activities for optimizing CiPA recommended protocols in patch clamp assays”, Katayama Y, Matsukawa H, Kanehisa T, Abe A, Yoshinaga T, Asakura K, Yoshikawa K, Tsurudome K, Tsukamoto T, Nissan Chemical, Japan Tobacco Inc., Eisai Co., Nippon Shinyaku, LSI Medience corp.and Sophion Bioscience (LINK)

Posters from ICMS2019 in Cambridge UK now online

Nine posters from ICMS 2019 in Cambridge UK are online. Thank you to the authors for the contribution to make this years meeting another success

 

  • Cole BA et al 2019. Structure-based identification of novel KNa1.1 inhibitors (Uni of Leeds)
  • Chakrabarti et A l 2019. In vitro inflammatory knee pain: Of Mice and Men (Uni of Cambridge)
  • McCoull et Al 2018. Development of a novel screening system to identify activators of Two-pore domain potassium channels (K2Ps) (LifeArc)
  • Moreels L et al 2019. Generating potent and selective inhibitors of Kv1.3 ion channels by fusing venom derived mini proteins into peripheral CDR loops of antibodies (Iontas)
  • Marklew A et al 2019. Development and validation of NMDA ligand-gated ion channel assays using the Qube 384 automated electrophysiology platform (Charles River Laboratories)
  • Rosholm et al 2019. Characterization of hiPSC-derived neurological disease models using automated patch clamp (Qube and QPatch) (Sophion)
  • Sauter D et al 2019. Biophysical and pharmacological profiling of multiple voltage-gated sodium channel subtypes on QPatch II (Sophion)
  • Williams S and Kammonen J 2019. Adaptive voltage protocols increase precision of voltage-gated ion channel measurements on highthroughput automated patch clamp platforms (Charles River Laboratories)
  • Schombert B et al 2019. A pharmacological synopsis of small molecules, toxins and CiPA compounds targeting human cardiac Kv4.3 channels (Sanofi)

Find them here 

iPSC-derived motor neurons on Qube and QPatch

High success rates and significant differences in diseased versus control cells from Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy patients open for a whole new role for automated patch clamp in relation to neurological diseases. BrainXell has provided cells enabling this work.

Read the report here.

Simultaneous recordings from hERG and Nav1.5

Pfizer safety department demonstrated that it is possible to mix Nav1.5 and hERG cells using multi-hole QChips on Qube. The high success rates combined with the different electrophysiological properties of those channel types gives a very high correlation between this technique and if they are tested in single-cell assays.

See the poster here

New application report: Perforated patch recordings on Qube 384

Would you like to fight run-down but think perforated whole-cell is not possible on a 384-instrument? We have made a new application report with a thorough description of how to make perforated patch experiments on Qube using either of four different perforating agents.

For the full report please click here 

New assay created by Metrion: Nav1.5(Late) cardiac safety on QPatch

Using the QPatch, Metrion has created and validated a NaV1.5(late) assay that removes the requirement for pharmacological enhancers of NaV1.5(Late) and, thereby, delivers improved cardiac safety screening reliability and cost. Read the report here.

Congratulations to our latest Ph.D student Jiaye Zhang

Big congrats to Jiaye Zhang who successfully received his Ph.D. degree for his thesis entitled “Development of an Optogenetic System for Ion Channel Studies” from Cranfield University.

Great that Ph.D. students can come to Sophion and start up new exciting work. In this case Jiaye’s project was prework and inspiration for the Qube Opto solution.

We are also very happy that Jiaye is well underway, currently working at the Chinese Academy of Sciences as a Post Doc within neuronal stem cells.

8 hours unattended hERG screening with >97% success rates

With Qube 384 fitted with stacker and temperature control and with a good hERG cell line, you can perform unattended experiments for more than 8 hours with a single click on “run”. Quality control is applied automatically and results in not less than a minimum of 97% of successful experiments from each plate with an average Z’ value of 0.76 demonstrating a very large screening window.

During prolonged unattended runs the Qube stacker will feed QChips and compound plates, while the temperature control ensures a stable temperature around the cells (in this case 25 °C).

Want to know more? Read the full report here.

New papers, posters and reports from Q1 2019

Learn more about how you can use Sophion patch clamp to characterize iPSC-Derived Motor Neurons in ALS disease models. Learn about our optogenetic Qube, ion channels in cancer, and much more from academic and pharma researchers, from among others Amgen, Axxam, Sanofi, Kings College London, BrainXell etc.

 

Peer-reviewed papers

D Wang et al 2018. Synthesis of Pseudellone Analogs and Characterization as Novel T-type Calcium Channel Blockers. Mar. Drugs, 16(12), 475

B Kaproń et al 2018. Development of the 1,2,4-triazole-based anticonvulsant drug candidates acting on the voltage-gated sodium channels. Insights from in-vivo, in-vitro, and in-silico studies. European Journal of Pharmaceutical Sciences Vol 129, Pages 42-57

S Yadav et al 2018. Benzothiophenes as Potent Analgesics Against Neuropathic Pain. Biochemical and Biophysical Roles of Cell Surface Molecules, Advances in Experimental Medicine and Biology 1112

Reyes-Corral et al 2019. Differential Free Intracellular Calcium Release by Class II Antiarrhythmics in Cancer Cell Lines. The Journal of Pharmacology and Experimental Therapeutics [17 Jan 2019, 369(1):152-162]

Miner et al 2019. Drug Repurposing: The Anthelmintics Niclosamide and Nitazoxanide Are Potent TMEM16A Antagonists That Fully Bronchodilate Airways. Frontiers in Pharmacology, Vol 10, Article 51

Das et al 2019. Novel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis. Nature Scientific Reports, Vol 9, Article 2904

Sanson et al 2019. Electrophysiological and Pharmacological Characterization of Human Inwardly Rectifying Kir2.1 Channels on an Automated Patch-Clamp Platform. Assay Drug Dev Technol. 2019 Mar

Bagchi et al 2019. Disruption of Myelin Leads to Ectopic Expression of KV1.1 Channels with Abnormal Conductivity of Optic Nerve Axons in a Cuprizone-Induced Model of Demyelination

Posters:

Sauter et al 2019. Biophysical and Pharmacological Profiling of Multiple Voltage-Gated Sodium Channel Subtypes on QPatch II. Poster, Biophysics 2019

Rosholm & Schupp 2019. iPSC-Derived Motor Neurons on the Automated Patch Clamp Platforms Qube and QPatch. Poster, Biophysics 2019

Boddum et al 2019. Optical modulation of ion channels using Qube Opto. Poster, Mammalian Sensory Systems 2019

Application Reports:

Boddum, Korsgaard 2019. Pharmacological evaluation of GABAA receptor subtypes on Qube 384. Sophion Application Report

 

Read the latest news on Qube, QPatch II and much more

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Pharmacological evaluation of GABAA receptor subtypes on Qube 384

Ligand-gated experiments require many compound additions for incubation, stimulation, test drug and combinations thereof. Enabling that in 384-format tremendously enhances the throughput which is necessary to find the interesting new NAMs, PAMs or other types of compounds.

Here we report studies of three subtypes of GABAA channels using Qube 384 and with focus on:

  • Short ligand exposure with repetitive stimulations with EC50 concentrations of GABA
  • Effects of agonists, antagonists and modulators
  • Cumulative and non-cumulative concentration-response relationships
  • Characterizing the pharmacological properties of four cell lines expressing different GABAA subtypes

For the full application report, please see here.

Get the most out of your APC instrument

Sophion instruments are easy to use but there is always something new you can learn. We provide training courses for QPatch and Qube so that you can get better at setting up assays, running the instrument overnight and just all the power in Sophion Analyzer to get all the information from your recordings.

The courses will take place at Sophion in Japan, USA and Denmark starting in Copenhagen, DK on 1st May. We plan to do the courses in Japan and the USA in October. You are welcome to participate if you have a Sophion instrument and for Platinum and Gold service contract customers participation is free of charge.

Contact your application scientist for more information. You can register for the 1st May training here:

Two new posters by Charles River Laboratories on HTS ion channel screening

Using the stacked solution technology Charles River have developed and validated an assay suited for high through screening on both P2X- and GABA receptors. The short exposure of ligand of less than 1 second enables repetitive stimulation which is necessary for this assay. In another assay with voltage-gated target, the vast number of parameters that can be measured with high fidelity e-phys makes it important that the underlying software is powerful enough to cope. Read more here for ligand-gated and here for the NaV1.1 assay.

New Qube software version Eagle released

We have listened to all of our users and implemented a long range of new features – actually, more than 260 feature requests have been met. The most exciting is the ‘first in the 384-world’ individually adapting protocols. This means that you can ask Qube to record from any cell at its own specific voltage of e.g. half maximal activation. This creates very tight data and potential to select your compounds with the right mode of action a lot easier and faster.

Cancer cell membrane potential controlled by Wnt peptides

Wnt ligands play important functional roles during development and in disease. Binding of Wnt to the cell membrane receptors which starts a signalling pathway was made by using QPatch and single cell patch recording.

The findings suggest that Wnt control of membrane potential is a signal amplifying mechanism for low nanomolar levels of Wnt, and modulation of this cell signal transduction pathway could be critical for gene transcription and cellular function. See the poster here.

hiPSC motor neurons on Qube and QPatch

Neurological diseases like Amyotrophic Lateral Sclerosis are detrimental in their nature and not easy to treat. In the search for new interventions it is necessary with model systems to test molecules, genetic modifiers etc. We can record both healthy, diseased and rescued hiPSC on our instruments. Read more here.

Biophysical and pharmacological profiling of multiple voltage-gated sodium channel subtypes on QPatch II

Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell’s plasma membrane.

In this poster, we show biophysical and pharmacological profiling of Nav1.1-8. The study used QPatch ll in combination with adaptive voltage protocols to investigate state-dependent inhibition of tetrodotoxin (TTX), amitriptyline and tetracaine on 8 different VGSC subtypes (NaV1.1-8). We also demonstrate the feasibility to determine the half-inactivation potential V½ (inactivation) for each individual cell. This value was then used during the next steps as a preconditioning pulse. Such an adaptive protocol allowed to determine IC50 values for both the closed and the inactivated state and reduce heterogeneity of the cells.

See the poster here.

Cav1.2 on Qube, no rundown

High success rates and minimal rundown with pharmacology according to literature values. The third CaV1.2 cell line, this time kindly provided by Charles River, helps demonstrate how Ca-currents can be recorded stably on automated patch clamp. So, whether you want to investigate the CiPA protocol, interrogate for state dependent mode of action or biophysical characteristics, Qube is the enabling technology. See the full report here.

2018 in review – another great year has passed

Looking back at 2018 it was another year that was fun and rewarding, but also extremely busy.

But who cares when busy also means happy users, interesting publications, new products and many new installs.

Click to get a brief overview of 2018 from a Sophion perspective.

We are looking forward to 2019.

Season’s greetings

Brisbane Pain Research Symposium on 7th December

We are happy to assist in making the Brisbane Pain Research symposium on 7th December a success. The aim of this symposium is to stimulate scientific discussion, collaboration and ongoing engagement to advance pain research and treatments. What’s not to like. For more information see here.

GABA receptors – HTS electrophysiology and optopharmacology on primary cells and stable cell lines

GABA is an important neurotransmitter in CNS, which controls most of the functions of the body and mind. It’s has been implicated in several health challenges such as anxiety disorders, insomnia, or depression. In this poster, we show pharmacological modulation of GABAAR using QPatch and Qube 384. The study includes a characterization of the heterogeneous GABAAR population of cultured primary hippocampal astrocytes and an evaluation of the GABAAR clone ɑ5β3γ2.

The results demonstrate the feasibility of performing GABAAR-targeted drug-screening on Qube and QPatch, and we also introduce optopharmacology as a viable application possibility for high-throughput pharmacological experiments.

See the poster here.

Qube and QPatch posters presented at SPS 2018

A total of six posters with results from Qube and QPatch were presented at the SPS annual meeting in Washington DC covering cardiac safety channels:

Sophion exhibiting in South Korea for the first time

For the first time ever, Sophion attended a conference with a booth in South Korea at The 70th Annual Meeting of the Korean Physiological Society, held from 25th to 27th October 2018 in Wonju city, South Korea.

The exhibition was organized in cooperation with our South Korean distributor Sure Medical. Inc. and was a great success with plenty of booth traffic and interesting discussions.

Diseased and control hIPSC motor neurons measured on Qube and QPatch

Motor neurons control essential voluntary muscle activity such as speaking, walking, breathing, and swallowing. Motor neuron diseases (MND) are a group of progressive neurological disorders that destroy motor neurons. Some MNDs are inherited, but the causes of most MNDs are not known.

Being able to measure and screen on diseased and wildtype hIPS motor neurons have long been requested from many of our users.

In this new poster just presented at “Neuroscience 2018” we show that measurements on normal and diseased motor neurons are possible with good success rates on both Qube and QPatch

  • Electrophysiological properties of hiPSCs from Spinal Muscular Atrophy (SMA) or Amyotrophic Lateral Sclerosis (ALS) patients was measured and compared to their control cell lines
  • ALS disease cells exhibit a significantly increased NaV current as compared to the control, which could be rescued by a single point mutation.

Find it here

Sophion Seminar in Japan

Friday 19th October we hosted the annual Sophion Seminar in Tokyo. More than 40 interested visitors were there to hear interesting talks and see the QPatch II for the first time in Japan.

QPatch II was presented to the audience and among others, Prof. Koichi Nakajo gave an educational lecture on “Stochiometry and function of potassium channel auxiliary subunits”.

Also, Juha Kammonen from Charles Rivers, UK gave a talk on how they at Charles River have successfully implemented the Qube into their ion channel drug discovery screening cascade, and he presented example data from both a high throughput screening campaign and a hit-to-lead project.

CMIC Pharma Science was hosting the meeting – the settings were fantastic for the reception party that followed the meeting.

QPATCH II AUTOMATED PATCH CLAMP

Come and see our brand new QPatch II

We look forward to greet you at our booth #1933 at the Neuroscience annual meeting in San Diego. Make sure to ask one of our ion channel experts for a demo of QPatch II.

Read more about our activities at the conference here.

See you in San Diego in November.

 

31 new Publications and Reports from Q3

We have been informed that we missed a few publications from the Q3 list we posted some weeks ago. Thanks for letting us know…thats what friends are for.

Here is the (hopefully) complete list of publications from Q3 (and a part of Q2).

Learn more about how cannabis inhibits Nav currents at therapeutically relevant concentrations or venom from the giant red bull ant published by, among others, Xenon Pharmaceuticals, GSK, AstraZeneca, Sanofi, Eisai, Uni Queensland and more

Peer reviewed publications

  • Sokolov et Al 2018. Co-expression of β Subunits with the Voltage-Gated Sodium Channel NaV1.7: the Importance of Subunit Association and Phosphorylation and Their Effects on Channel Pharmacology and Biophysics. Journal of Molecular Neuroscience (LINK)
  • Kanase et Al 2018. 4-Substituted carbamazepine derivatives: Conformational analysis and sodium channel-blocking properties. Bioorganic & Medicinal Chemistry, Volume 26, Issue 9 (LINK)
  • Gonçalves et Al. 2018. Direct evidence for high affinity blockade of NaV1.6 channel subtype by huwentoxin-IV spider peptide, using multiscale functional approaches. Neuropharmacology, Volume 133, 404-414 (LINK)
  • Zha et Al. 2018. Design, synthesis and biological evaluation of tetrahydronaphthyridine derivatives as bioavailable CDK4/6 inhibitors for cancer therapy. European Journal of Medicinal Chemistry, Volume 148, Pages 140-153 (LINK)
  • Israel et Al. 2018. The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and Excitatory Activities on Human NaV1.6. J. Med. Chem., 2018, 61 (4), pp 1730–1736 (LINK)
  • Loucif et Al. 2018. GI‐530159, a novel, selective, mechanosensitive two‐pore‐domain potassium (K2P) channel opener, reduces rat dorsal root ganglion neuron excitability. British Journal of Pharmacology (LINK)
  • Xu et Al. 2018. Synthesis and biological evaluation of a series of multi-target N-substituted cyclic imide derivatives with potential antipsychotic effect. European Journal of Medicinal Chemistry, Volume 145, Pages 74-85 (LINK)
  • Agwa et Al 2018. Efficient Enzymatic Ligation of Inhibitor Cystine Knot Spider Venom Peptides: Using Sortase A To Form Double-Knottins That Probe Voltage-Gated Sodium Channel NaV7. Bioconjug Chem. 2018 Sep 12. (LINK)
  • Colley et Al 2018. Screening strategies for the discovery of ion channel monoclonal antibodies. Current Protocols in Pharmacology, 82, e44. (LINK)
  • Robinson et Al 2018. A comprehensive portrait of the venom of the giant red bull ant, Myrmecia gulosa, reveals a hyperdiverse hymenopteran toxin gene family. Science Advances 12 Sep 2018:Vol. 4, no. 9 (LINK)
  • Procopiou et Al 2018. Discovery of (S)-3-(3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a Nonpeptidic αvβ6 Integrin Inhibitor for the Inhaled Treatment of Idiopathic Pulmonary Fibrosis. Med. Chem (LINK)
  • Ghovanloo et Al 2018. Inhibitory effects of cannabidiol on voltage-dependent sodium currents. Journal of Biological Chemistry (LINK)
  • Bankar et Al 2018. Selective Nav1.7 Antagonists with Long Residence Time Show Improved Efficacy against Inflammatory and Neuropathic Pain. (LINK)

Posters

  • Bettini et Al 2018. NMDA Receptor Modulators in QPatch. Evotech Gmbh (LINK)
  • Boddum et Al 2018. Optical modulation of ion channels. Sophion Bioscience. (LINK)
  • Boddum et Al 2018. GABAA receptor pharmacology evaluted in overexpressing HEK cells and primary astrocytes on QPatch. Sophion Bioscience. (LINK)
  • Standing et Al 2018. Development of high-throughput electrophysiological assay for the screening of hERG ion channel modulators using Sophion Qube 384. GlaxoSmithKline (LINK)
  • Klint et Al 2018. HT Automation for patch clamp based primary screen for Nav1.1 using Qube 384. Lundbeck A/S (LINK).
  • Bouyer and Hebeisen 2018. NaV5 big late : An inactivation deficient mutant of NaV1.5 as screening tool for late sodium currents of the cardiac action potential. B’SYS (LINK)
  • Douglin Guo et Al. 2018 Simultaneous measurement of cardiac Nav5 peak and late current in an automated QPatch platform. Pfizer. SPS 2018
  • Koci et Al 2018. Optimization of Cardiac CiPA targets (Cav2 and KCNQ1/MinK) on the QPatch HT automated system. Eurofins. SPS 2018
  • Huphries et Al 2018. New CiPA ion channel cell lines and assays for in vitro proarythmia risk assessment. Metrion Biosciences. SPS 2018. (Will be uploaded soon)
  • Donglin Guo et Al 2018. Simultaneous measurement of cardiac hERG and Nav5 currents using an automated Qube patch clamp platform. Pfizer. SPS 2018. (Will be uploaded soon)
  • Renganathan et Al 2018. Automated High Throughput Na+ Late current Assay on QPatch HT platform for CiPA28. Eurofins. SPS 2018 (Will be uploaded soon)
  • Lindqvist and Christensen 2018. Estimating hERGdrug binding using temperature-controlled high throughput automated patch clamp. Sophion Bioscience. SPS 2018 (Will be uploaded soon)

Application Reports

  • Humphries and Binzer 2018. CiPA hERG Milnes kinetic assay on Qpatch (LINK)
  • Sauter D 2018. Voltage and current clamp recordings of Cor.4U® human iPS cell-derived cardiomyocytes using Sophion’s QPatch (LINK)
  • Boddum K 2018. Ligand gated ion channels: GABAA receptor pharmacology on QPatch (LINK)
  • Sauter D 2018. Human iPS cell-derived cardiomyocytes (Cor.4U®) on Sophion’s Qube 384: voltage and current clamp recordings (LINK)
  • Rosholm & Schupp 2018.2 recordings using QPatch (LINK)
  • Schupp 2018. 8 hours unattended hERG run with ≥97% success rate and consistent pharmacology results (LINK)

Mechanism of action elucidated with Qube

Two papers were recently published mechanistic studies; in Inhibitory effects of cannabidiol on voltage-dependent sodium currents Xenon together with Simon Frasier University used temperature control on Qube to describe the potency and mechanism of cannabidiol binding to voltage-gated sodium channels. Interestingly the potency is higher at lower temperatures. In Selective Nav1.7 Antagonists with Long Residence Xenon together with Genentech describe the mechanism of several of their compounds in selectively inhibiting Nav1.7, which is relevant in relation to inflammatory and neuropathic pain. These compounds act very slowly, but Qube allows more than one hour long experiments with very good voltage control during the whole experiment or as the authors state:

“Appropriate filters for minimum seal resistance and minimum current size were applied, and series resistance was compensated >80% to yield high- quality sodium channel recordings on par with manual voltage clamp techniques”

Qube is designed for drug discovery

We asked one of our customers how they screen several hundred thousands of compounds with high fidelity electrophysiology?

“We let the Qube run our large screening campaigns unattended during the night so we can run and develop other assays on the same instruments during the day”

Juha Kammonen, Principal Scientist, Charles River Laboratories

QPatch II attracts a full house in Washington DC

QPatch II has it’s first public show at the Safety Pharmacology Society annual meeting in Washington DC the last few days.

It has been very well received by the many current and future users that have passed by the booth for a demonstration. Most are excited by the new icon-based operator software, that makes operation even easier, but also the speed, the reduced cell consumption and the preloaded standard protocols. And the looks off course. Isn’t she a beauty? Besides that, we have had excellent feedback on the new online V½ estimation…. The first QPatch II has been sold and we are we are currently producing more so you all can have something cool under your Christmas tree this year.

Read more here

CiPA recommended Milnes kinetic hERG assay on QPatch

Up to now, only high-fidelity manual patch clamp recordings have been used to reliably measure hERG channel binding kinetics and drug trapping, both important aspects of drug action and potency as well as cardiac liability.

We have together with Metrion Biosciences implemented the challenging Milnes hERG cardiac safety assay on QPatch.

The Milnes assay meets the FDA’s CiPA requirements for improved arrhythmia prediction and data has a very good correlation with FDA’s manual patch clamp data.

  • High fidelity QPatch hERG kinetic data closely mimics FDA’s manual patch clamp Milnes protocol data
  • Stable hERG current profile during repetitive long depolarizing test pulses
  • The assay can detect changes in hERG amplitude and decay kinetics due to drug binding and trapping
  • Pharmacologically validated with clinical drugs showing a wide range of drug trapping activity

Download the application report here

New papers, posters and reports (Q3 2018)

Papers:

  • Sokolov et Al 2018. Co-expression of β Subunits with the Voltage-Gated Sodium Channel NaV1.7: the Importance of Subunit Association and Phosphorylation and Their Effects on Channel Pharmacology and Biophysics. Journal of Molecular Neuroscience (LINK)
  • Kanase et Al 2018. 4-Substituted carbamazepine derivatives: Conformational analysis and sodium channel-blocking properties. Bioorganic & Medicinal Chemistry, Volume 26, Issue 9 (LINK)
  • Gonçalves et Al. 2018. Direct evidence for high affinity blockade of NaV1.6 channel subtype by huwentoxin-IV spider peptide, using multiscale functional approaches. Neuropharmacology, Volume 133, 404-414 (LINK)
  • Zha et Al. 2018. Design, synthesis and biological evaluation of tetrahydronaphthyridine derivatives as bioavailable CDK4/6 inhibitors for cancer therapy. European Journal of Medicinal Chemistry, Volume 148, Pages 140-153 (LINK)
  • Israel et Al. 2018. The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and Excitatory Activities on Human NaV1.6. J. Med. Chem., 2018, 61 (4), pp 1730–1736 (LINK)
  • Loucif et Al. 2018. GI‐530159, a novel, selective, mechanosensitive two‐pore‐domain potassium (K2P) channel opener, reduces rat dorsal root ganglion neuron excitability. British Journal of Pharmacology (LINK)
  • Xu et Al. 2018. Synthesis and biological evaluation of a series of multi-target N-substituted cyclic imide derivatives with potential antipsychotic effect. European Journal of Medicinal Chemistry, Volume 145, Pages 74-85 (LINK)
  • Agwa et Al 2018. Efficient Enzymatic Ligation of Inhibitor Cystine Knot Spider Venom Peptides: Using Sortase A To Form Double-Knottins That Probe Voltage-Gated Sodium Channel NaV7. Bioconjug Chem. 2018 Sep 12. (LINK)
  • Colley et Al 2018. Screening strategies for the discovery of ion channel monoclonal antibodies. Current Protocols in Pharmacology, 82, e44. (LINK)
  • Robinson et Al 2018. A comprehensive portrait of the venom of the giant red bull ant, Myrmecia gulosa, reveals a hyperdiverse hymenopteran toxin gene family. Science Advances 12 Sep 2018:Vol. 4, no. 9 (LINK)
  • Procopiou et Al 2018. Discovery of (S)-3-(3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a Nonpeptidic αvβ6 Integrin Inhibitor for the Inhaled Treatment of Idiopathic Pulmonary Fibrosis. Med. Chem (LINK)

 

Posters:

  • Bettini et Al 2018. NMDA Receptor Modulators in QPatch (LINK)
  • Boddum et Al 2018. Optical modulation of ion channels (LINK)
  • Boddum et Al 2018. GABAA receptor pharmacology evaluted in overexpressing HEK cells and primary astrocytes on QPatch (LINK)
  • McCoull et Al 2018. Development of a novel screening system to identify activators of Two-pore domain potassium channels (K2Ps)(LINK)
  • Standing et Al 2018. Development of high-throughput electrophysiological assay for the screening of hERG ion channel modulators using Sophion Qube 384 (LINK)
  • Klint et Al 2018. HT Automation for patch clamp based primary screen for Nav1.1 using Qube 384. (LINK)
  • Bouyer and Hebeisen 2018. NaV5 big late : An inactivation deficient mutant of NaV1.5 as screening tool for late sodium currents of the cardiac action potential (LINK)

 

Application reports:

  • Sauter D 2018. Voltage and current clamp recordings of Cor.4U® human iPS cell-derived cardiomyocytes using Sophion’s QPatch (LINK)
  • Boddum K 2018. Ligand gated ion channels: GABAA receptor pharmacology on QPatch (LINK)
  • Sauter D 2018. Human iPS cell-derived cardiomyocytes (Cor.4U®) on Sophion’s Qube 384: voltage and current clamp recordings (LINK)
  • Rosholm & Schupp 2018. Cav1.2 recordings using QPatch (LINK)
  • Schupp & Korsgaard 2018. 8 hours unattended hERG run with ≥97% success rate and consistent pharmacology results (LINK)

 

Introducing QPatch II

QPatch has been the benchmark automatic patch clamp solution for cardiac safety and advanced electrophysiology since the early 00’s.

With the new QPatch II we raise the bar for efficiency and usability, while maintaining the proven data quality from QPatch.

If you want to find out how QPatch II can increase the efficiency in your ion channel lab, come visit our booth #113 at SPS in Washington or send a mail to info@sophion.com to book a private demo

 

Did you miss the Ion Channel Modulation Symposium in June?

We video recorded most of the talks for you to watch on our website. Just click here, sit back and enjoy

Sophion co-organized channelopathy symposium in China

In mid-July Sophion Bioscience co-organized a meeting at the University of Peking entitled

“International Symposium on channelopathy and drug discovery – Ion channels as drug targets”

The meeting was hosted by the State Key Laboratory of Natural and Biomimetic Drugs, Health Science Center of Peking University.

The aim was to provide a platform for communication and knowledge exchange in channelopathy area for basic researchers, doctors, and pharmaceutical companies in China. Chinese and international speakers was invited to give presentations on novel scientific ideas, cutting‐edge technologies and latest research achievements on ion channels as well as the relevant diseases. Our own Application Scientist Melanie Schupp also gave a talk on “Nav1.1 in high throughput screening”.

It was a great pleasure for us at Sophion to co-organize this event in China and we were happy to see the large attendance from engaged researchers.

For full program and speaker biographies see here (It takes a while to load)

Sophion User Meeting Europe 2018 – sign up now!

Sign up for the Sophion User Meeting 2018 on 5th and 6th September now. You can read much more about the event here.

 

Sophion Japan website is now live!

新しくなったSophionのウエブサイトに、日本からアクセス頂いたお客さまを歓迎いたします。このたびSophionでは、当社の製品に関連した文献、アプリケーションレポート、学会発表ポスター、そしてイオンチャネル研究分野における最新情報を取りまとめたリソースライブラリを、日本語環境でも皆さまにご利用頂けるよう、ウエブサイトをリニューアルいたしました。当社の新しいウエブサイトにてご提供する情報が、皆さまのご研究の一助となれば幸いです。

To reflect our growing customer base in Japan we are happy to introduce our new Japanese version of www.sophion.com. The new Japanese website ensures that also our Japanese customers and partners have access to our publication database with posters, publications and application reports, as well as our application database where you can browse content grouped by ion channel type or disease area.

ICMS2018 – thank you very much

We would like to thank you for participating at the 3rd Sophion Ion Channel Modulation Symposium in Cambridge last week. We truly appreciate that you took the time to attend and we hope you enjoyed yourselves as much as we did. A special thanks to our sponsors; Roche, MaxCyte, SB Drug Discovery, B’SYS, Charles River and Metrion for being part of ICMS2018. And last but not least a huge thanks to the speakers and the advisory board whom all contributed making the event a success. See you on 19th and 20th June next year.

Super-short ligand exposure time on Qube Opto 384

With the new optical capability of Qube Opto in combination with the microfluidic system of the QChip, the exposure time of a ligand can be drastically reduced. Here we use rubi-GABA, a caged GABA compound, and demonstrate two strategies to obtain short ligand exposure.

RuBi-GABA activation followed by wash-out

When 1mM RuBi-GABA is washed in, no response is seen, as the caged GABA does not activate the GABA receptors. Upon stimulation with light for 100 ms, GABA is uncaged and activates the GABAA receptor. 500 ms after the stimulus, the microfluidic channel is flushed, the response terminated, and the channels are completely deactivated.

HEK 293 / GABAA (α5β3γ2) Caged GABA (Rubi-GABA – Tocris). Light stimulus 475 nm, 100 ms. Compound consumption: 7 µL/site

RuBi-GABA activation during perfusion

To further decrease the ligand exposure time, the light stimulation was executed during perfusion with RuBi-GABA. The uncaged GABA was instantaneously washed out, and in combination with a shortening of the light stimulus to 20ms, a sharp, ultrashort GABA response was recorded with an exposure time approaching that of a synaptic response.

HEK 293 / GABAA (α5β3γ2)
Caged GABA, 330µ (Rubi-GABA – Tocris)
Light: 475 nm, 20 ms
Compound consumption: 7 µL/site

 

Updated privacy policy

We have also updated our privacy policy in relation to the new requirements (GDPR).

In short:

  • We only collect personal information to facilitate commercial engagements with you or to provide you with the world class service that is expected from us.
  • You can always ask us to correct, change or delete personal data, and unsubscribe to news by clicking the “unsubscribe button” in the footer of all our communication.

So all in all…. no changes on our side. We will continue to handle your personal information with integrity and respect

You can read the full privacy policy here

hCav1.2 recordings using QPatch

The development of screening assays for the CaV1.2 channel has been challenging due to the tendency of the channel to exhibit declining current levels (rundown) during the experiment. Here we report about a robust CaV1.2 QPatch assay yielding high success rates, low rundown and reliable pharmacology.

  • Pharmacology and current-voltage relationship in accordance with literature values
  • Success rates of up to 98%
  • Stable currents with rundown as low as 2% per minute
  • For the full application report please see here.

ICMS 2018 coming up shortly…..

We look very much forward to seeing so many people again in Cambridge for the third Ion Channel Modulation Symposium. All the tickets have been sold out for quite a while, but you can still register on our waiting list – there may be cancellations.

You can see the full agenda here. Please click here if you’d like to see some of the great talks from last years’ ICMS.

GABAA pharmacology on cell lines and primary astrocytes on QPatch

In this new Sophion Application report  GABA receptor pharmacology was evaluated on QPatch. We did thorough compound evaluations in a GABAA(α5β3γ2) cell line and investigated the GABA response of primary hippocampal rat astrocytes with emphasis on:

  • Effects of agonists, antagonists, and modulators
  • Concentration-response relationships
  • EC50 and IC50 determination
  • Characterizing both the pharmacology of a specific isolated GABAA subtype and the physiological GABA response of cultured rat astrocytes

Read the full report here.

Also, you are welcome to check out our other publications on GABA here.

Light activated rubi-GABA on Qube Opto 384

The new optical capability of Qube Opto introduces the possibility of employing optopharmacology in combination with patch clamp in a 384 format. As we continue to challenge our system we will present some of the results here. Recently we have been playing with experiments employing rubi-GABA, a caged GABA compound activated by visual wavelengths.

GABAAR mediated currents was elicited by optical uncaging of GABA in both a concentration and light dependant fashion.

Stay tuned for more news on Qube Opto 384 in the coming weeks

Concentration-response relationship

  • HEK 293 / GABAA5β3γ2)
  • Caged GABA (Rubi-GABA – Tocris)
  • Light: 475 nm for 200 ms @ 100% light output intensity
  • Rubi-GABA: 3-fold dilution series
  • EC50: 10,6 uM +/- 0,5 uM

Optical dose-response relationship

  • HEK 293 / GABAA5β3γ2)
  • Caged GABA (Rubi-GABA – Tocris)
  • Light: 475 nm for 200 ms @ 10-100% light output intensities
Optical Dose Response relationship. Left: Current traces at 10%, 33% and 100% light intensity. Right: Response as a function of light intensity

See application report here.

For more information on Optogenetic capabilities on Qube Opto 384 contact SWI@sophion.com

Cor.4U® human iPS cell-derived cardiomyocytes

Cor.4U human iPS cell-derived cardiomyocytes on QPatch and Qube

Two new application reports with Cor.4U® human iPS cell-derived cardiomyocytes from Ncardia on QPatch and Qube.

The hiPSC – CM provide new strategies to assess cardiotoxicity in vitro and different technologies are available to assess compound effects on cardiomyocytes.

Here we demonstrate

  • High throughput and high fidelity voltage and current clamp recordings
  • Presence of INa, ICa and IKr
  • Paced and spontaneous action potentials
  • We also show that the use of fluoride in the internal solution resulted in lower ICa and shortened action potential durations on QPatch.

See the report for QPatch (Link) and for Qube (Link)

Also, you are welcome to check out our other publications on stem cells here

Orion with their brand new Qube

How easy is it to use Qube?

At Sophion we believe that ease of use is important. When a customer spontaneously express clear appreciation of how easy it is to use our systems, we know we got it right:

“It was true that it’s really up and running after two days training. We are very pleased”

Maija Ivaska, Research Assistant, Orion Pharma

Ease of use does not come by itself with sophisticated electrophysiological recordings in automated patch clamp, but is embedded in the Sophion DNA.

Ask for a demo anywhere in the world to experience this yourself. We are so confident that you will be allowed to run your own experiments at the end of the first day….and that is not always the case with APC instruments.

With our instruments you can perform experiments with a very low risk of human error and large degree standardization, enabling easy learning, many operators and high laboratory efficiency.

Read more about Qube here.

Qube Opto 384 – for optical stimulation of ion channels or compounds.

Optical stimulation combined with Automated Patch Clamp allows for precise control of e.g. channelrhodopsins, caged compounds and pacing studies. To allow for even better control than with our standard APC solutions, we have now integrated 384 adjustable LEDs to allow for optical stimulation of ion channels, ligands or compounds.

To compensate for heating due to the large amount of energy released, we have adapted our on-site temperature control, so temperature effects are reduced to a minimum.

To avoid desensitization from ambient light we have darkened the cabinet so Qube looks even cooler, having a distant resemblance to a well-known character from a movie happening in a galaxy far, far away.

  • 384 LEDs to ensure consistent and even light distribution throughout all 384 sites
  • Light ramps and other waveforms through adjustment of timing, duration and intensity of light
  • Integrated temperature control to avoid unwanted temperature effect
  • Full LED control integrated in Qube software
  • Dark cabinet allows for automated handling of light sensitive compounds and cells

During the coming months we will be playing with this new setup ourselves together with a few select partners. If you are also interested to discover the full potential of this setup and would like to come play with us, you are welcome to contact Sandra Wilson (swi@sophion.com) or visit booth #518 at Biophysics for more information.

Qube 384 and Qube Opto 384 – The darker cabinet on the Opto version is to avoid desensitization from ambient light and to ensure compliance to EU directives
Optical dose-response study with ten sweeps from 10% to 100% light intensity, show light saturation around 40-50% intensity
Light ramps or other waveforms can be defined directly in the Qube software for more advanced control

High throughput screening on Nav1.1 using Qube

The voltage-gated sodium channel NaV1.1 is highly expressed in fast spiking interneurons (FSIs), which are important for memory encoding and other cognitive functions. An impaired function of FSIs is associated with disorders like autism, schizophrenia, Alzheimer’s and others. Potentiators of NaV1.1 have been shown to minimize cognitive dysfunction in transgenic mice with decreased levels of NaV1.1 in parvalbumin-positive neurons and this target thus lend itself to therapeutic intervention. The challenge is to identify the molecule with the desired mode-of-action which inherently requires electrophysiology. In summary we show that Qube 384 provides:

  • Success rates up to 97%
  • Stable, unattended measurements over 7 hours
  • Consistent current voltage relationship
  • High reliability of detecting NaV1.1 activators

For the full application report please see here.

Welcome to our new field service engineer, Thomas Byrne

To ensure our customers continue to get the best service, especially with the increasing number of instrument purchases in North America, we are staffing up our Service Operation.

Thomas Byrne comes to Sophion from Olympus Scientific Solutions Americas where he was a systems engineer supporting clients worldwide onsite and remotely. He also worked as a Senior Field Service Engineer at Hospira Worldwide Inc supporting their products and services to hospitals in the Northeast.

We are very excited to have Thomas on board, and together with Lars Maul the two of them will continue to provide the best in class service to our customers as our business continues to grow.

Virtual Qube – Increase value from your CRO data

A Contract Research Organization will supply you with reports of your data. But in case you are interested in digging deeper into the immense value contained in high fidelity recordings from Qube, you can benefit for Qube External Data server solution.

Qube External Data server enables all the analysis needed to evaluate the results, from raw current traces, via current-time plots to Hill-fits of pharmacological effects or estimation of voltage of half maximal inactivation found on the Boltzmann-curve. If you want to export data e.g. to an inhouse database, this is also possible at all levels of data-maturity.

In case you have your own Qube, the analysis part is familiar and the use of the external data server could be segmenting large portions of data as well as release space on the internal data drive in Qube when that starts to fill up…however, we supply Qube with 8 TB memory and intelligent data reduction so it can take a while but good to know that it still shouldn’t limit you.

The Virtual Qube comes with two years free upgrade of Sophion software.

hCav1.2 recordings on Qube 384 using step, train and CiPA protocols

Some ion channels have a tendency to exhibit reducing current level in the course of an experiment. A notable member of this class is the CaV1.2 channel, a very important ion channel expressed in nervous tissue, the heart and smooth muscle and thus a target for a range of therapeutics as well as a liability target for other groups of medications. Therefore it is important to be able to record reliably, stably and with a high success rate in the pursue of novel compounds with the desired profile on CaV1.2 modulation. Qube 384 provides a stable assay with the CaV1.2 channel generated by SB Drug Discovery with these characteristics:

  • Pharmacology and current-voltage relationship in accordance with literature values
  • Success rates up to 94%
  • Stable currents with rundown as low as (1.2 ± 0.9)% per minute
  • The CiPA protocol yields stable currents with rundown as low as (1 ± 1)% per minute

For the full application report please see here.

Note that we have another Qube Application Report on Cav1.2 on another commercially available cell line underlining the robustness of the Qube platform. Find both of them here

For more information please contact info@sophion.com

Biophysics 2018 – here we come!

Time flies and soon BPS2018 will kick-off in San Francisco. We look forward to see you in San Francisco and hope that you will join us for the below events:

  • Satellite meeting – Friday, February 16th
  • Beer tasting and dining – Saturday, February 17th
  • Sophion Ion Channel meeting – Tuesday, February 20th
  • Poster presentation – Wednesday, February 21st

Read much more about each event here and make sure to sign up as the seats fill up quickly.

 

 

2017 in brief

What a year!

For Sophion it has been a year with many changes, a lot of news and countless achievements. It has also, by far, been the best year in the history of Sophion Bioscience and on behalf of the whole Sophion Bioscience team we would like to thank all our partners and customers for their continued support. Read more about 2017 seen from our perspective here “Sophion 2017 in brief

 

 

Happy New Year

We look very much forward to working with both new and old customers in 2018.

Registration for ICMS2018 is now open

Wednesday and Thursday 20th and 21st June, 2018 Sophion will be arranging and hosting the third Ion Channel Modulation Symposium at Clare College in Cambridge (UK) and it is now possible to register for the event.

Click here to read more.

We look forward to seeing you in Cambridge next June.

Santa’s little helpers…..?

No, this is not Santa Claus’ little helpers packing up toys for children, but our great production guys getting more systems ready for our happy customers.

Fast desensitizing ion channels recorded on Qube 384

Some ligand gated ion channels have a tendency to desensitize over time, making it difficult to establish a stable assay baseline. Rapid compound washout can counteract desensitization by reducing ligand exposure time to a minimum.

On Qube 384 the minimum washout is now less than 1 second (0.8 s), enabling stable assay for fast desensitizing ion channels.

With nAChRa1 as model, acetyl choline as agonist and tetracaine as test compound, a stable and high performance assay was established with:

  • Ligand exposure time 0.8 s
  • Whole-cell resistance of average 1.2 GΩ
  • Overall success rate of 89%
  • Very tight data – CV of ≤ 9% for control rows and columns
  • Z’ > 0.70
  • No desensitization observed

You can read the whole report here.

Five new QPatch publications from top pharma companies

The past month five new publications has been published from GSK, Pfizer, Gilead, Lundbeck and Acesion Pharma.

Donovan et Al 2017 – Discovery and electrophysiological characterization of SKF-32802: A novel hERG agonist found through a large-scale structural similarity search

Jenkinson et Al 2017- Cardiac sodium channel antagonism – Translation of preclinical in vitro assays to clinical QRS prolongation

Diness et Al 2017 – Termination of vernakalant-resistant atrial fibrillation by inhibition of small-conductance Ca2+-activated K+ channels in pigs

El-Bizri et Al 2017 – Eleclazine exhibits enhanced selectivity for long QT syndrome type 3–associated late Na+ current

Schoubye et Al 2017 – The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/− mice

Sophion user meeting in our new facilities in Japan

To accommodate the needs of a growing customer base in Japan, we have expanded our laboratory and demo space in our Japanese facilities in Honjo-Waseda. This was celebrated with a three day user meeting; two days with work shop and one day with seminar with great talks on science. Both the demo room with QPatch and Qube side by side as well as the conference room were in use to accommodate the approx. 30 users that wanted to learn about the latest tips, tricks and software for QPatch and Qube 384. A great success with active interaction and continuing into the evenings with delicious Japanese foods.

High throughput screening for mode-of-action on Nav1.7

A high-fidelity patch clamp set up is necessary to discover use-dependent mode of action. Qube is a second-generation automated patch clamp system that fulfils this requirement and allows for testing of many thousands of compounds per day in an unattended fashion. Using Qube in a drug development cascade allows asking the right questions during the primary screen, making a follow-up validation study obsolete. Some key points for a Qube screening like this are:

  • Giga-ohm seal
  • 99% average success rates
  • Very tight data
  • Discrimination between different modes-of-action

To read the full report click here

ICMS 2018

The dates have been fixed so mark your calendar for the 20th and 21st June, 2018. We look forward to seeing you at Clare College in Cambridge next year.

More information will be posted here shortly.

Eight new QPatch publications, two of them in Nature.com

A lot of new peer reviewed publications have seen the light over the summer. Here is some selected new publications. For more interesting publilcations on QPatch and Qube you can always search our publication database here

Huang et Al 2017 Synthesis and biological evaluation of novel 6,11-dihydro-5H-benzo[e]pyrimido- [5,4-b][1,4]diazepine derivatives as potential c-Met inhibitors

Kristof et Al 2017 An Official American Thoracic Society Workshop Report: Translational Research in Rare Respiratory Diseases. Official workshop report of the American Thoracic Society

Lazewska et Al 2017 Biphenyloxy-alkyl-piperidine and azepane derivatives as histamine H3 receptor ligands

Menegon et Al 2017 A new electro-optical approach for conductance measurement: an assay for the study of drugs acting on ligand-gated ion channels

Prashanth et Al 2017 Pharmacological screening technologies for venom peptide discovery

Sousa et Al 2017 Discovery and mode of action of a novel analgesic β-toxin from the African spider Ceratogyrus darlingi

Zhou et Al 2017 Design, synthesis and biological evaluation of 4,7,12,12a-tetrahydro-5Hthieno [3′,2’:3,4]pyrido[1,2-b]isoquinolines as novel adenosine 5′-monophosphate-activated protein kinase (AMPK) indirect activators for the treatment of type 2 diabetes

Zidar et Al 2017 Clathrodin, hymenidin and oroidin, and their synthetic analogues as inhibitors of the voltage-gated potassium channels

Poster presented at SPS in Berlin in September on temperature effect using Qube

Until recently, the only possibility to test compound potency under voltage control conditions has been the manual patch clamp technique. Now automated patch clamp instruments with temperature control have become available making it possible to perform up to 384 parallel recordings at controlled temperatures ranging from 8°C and above. Qube has a temperature controlled test environment and in these studies, we show that temperature merits being taken into consideration when evaluating for hERG pharmacology. See the poster here.

 

 

New faces at Sophion

To meet the increasing demand of new application development and customer support, we have hired two new application specialists.

Kim Boddum has a PhD in neuropharmacology and comes from a post doc at the Department of Biomedical Sciences at the Uni of CPH. Kim has for the past 7-8 years worked on membrane receptors and ion channels function and pharmacology.

Kadla Røskva Rosholm has a PhD in Nanoscience working on high-throughput fluorescence-based cell assays. Also she been done two post docs working on electrophysiological and fluorescence methodologies to investigate the molecular mechanism of ion-channel signaling.

You can meet Dr. Kadla Røskva Rosholm and Dr. Kim Boddum at customer sites, demos or conferences.

Qube 384 recordings with very short exposure time of ligand

Some like it slow, some like it fast. A Qube user wanted faster washout of activator in ligand-gated experiments and contacted their application scientist. We adapted the protocol in a matter of a week to obtain faster washout of ligand. That is how versatile the Qube Viewpoint software is. We thus reduced the ligand exposure time from 32 s to 0.8 s. The user has already used it and presented data on our Sophion User Meeting last week in Paris. Above is shown data from applying EC20 concentration of Acetylcholine to AChRa1 with the slow protocol (32 s) respectively the fast (0.8 s) protocol. There was not used esterases in any of the washouts. With the fast protocol it is clear that the current can be stimulated multiple times without desensitization.

Tecan publishing article about QPatch

We are proud to share with you an article published in Tecans latest journal about Sophion and our work with the QPatch. You can read the article here.

See some of the great talks from ICMS 2017 in Cambridge

We have the pleasure of sharing with you some of the great talks from the Sophion Ion Channel Modulation Symposium which took place in Cambridge in June.

See the talks here.

Enjoy

 

Temperature control on Qube 384 – pharmacological dependency of hERG reference compounds

Studies of temperature dependencies can be done efficiently and reliably on Qube 384. In this study we directly measure change in potency with change in temperature on four different compounds, emphasizing the importance of temperature when studying drug candidates.

See the new application report here.

Sophion Bioscience is acquired by Sophion CEO, management and investors

Sophion Bioscience has been acquired by Sophion CEO Thais T. Johansen, its management and a group of experienced investors.

Sophion was founded in 2000 as a spinoff from Neurosearch and have since the beginning been pioneering ion channel research and drug discovery. In 2004 Sophion launched the QPatch automated patch clamp solution, which still today is benchmark for advanced electrophysiology and cardiac safety in drug discovery. In 2013 Sophion Qube was launched taking automated patch clamp to the HTS space and taking automated patch clamping to a whole new level of usability. In between Sophion has continuously improved performance and capabilities and launched pioneering new features such as automated Rs compensation, automated current clamp, integrated cell preparation, etc.

Sophion was in 2011 acquired by Biolin Scientific Holding AB, a company owned by Swedish private equity firm Ratos AB.

Sophion CEO Thais Johansen states “Our new ownership structure and financial partners bring a long-term orientation and expertise in building a high-growth life science business. With this involvement, we are well-positioned to continue investing in innovation, technologies and people”.

Thais also said, “we will continue to build on the Sophion legacy with focus on quality, innovation and customer satisfaction” and continues “I am looking forward to talk to our partners over the next weeks to discuss these changes as well as discuss the many great news we have in pipeline”.

Sophion Bioscience employs approximately 60 people worldwide. It is headquartered in Copenhagen, Denmark and has subsidiaries in Boston, Tokyo and Shanghai, as well as distributors in Japan, India and Korea. Sophion has an install base of 100+ automated patch clamp systems and presence in more than 75% of the TOP20 largest Pharma companies in the world.

Sophion Bioscience, Inc. is in the building

ICMS2017 – thanks everyone for contributing

Another great Sophion Ion Channel Modulation Symposium meeting at the amazing Clare College. Knowledge sharing, socializing and presentations of new discoveries in our field from the top notch researchers from academia and pharma industry. …. and good food and beer not to mention. Great way to spend a week. ICMS2018 already in pipeline.

Ph.D. course at Sophion Denmark

Sophion was hosting a PhD summer school on cardiac electrophysiology Wednesday the 7th of June.
The course consists of 30 students from many different institutions all around Europe and will be in conjunction with a European Marie Sklodowska Curie training network.
The students will be introduced to our company and the spirit of Sophion Bioscience but will also learn about patch clamp technique and even get some hands-on experience with our high throughput devices.

QPatch automated patch clamp

New paper on KCa2.X (SK) on QPatch

Small conductance calcium-activated K+ channels (KCa2.X, SK channels) are promising new targets for the treatment of Atrial fibrillation (AF), the most common type of arrhythmia. In a collaboration with Acesion Pharma, Bo Bentzen and his group revealed an inhibitory effect of some established AF drugs on SK channels using Sophion`s QPatch.   The paper benefits from QPatch`s capability to gain gigaohm seal resistances without relying on the presence of seal enhancing fluoride in the internal solution.

Read more here

Interested in CFTR? ….or traditional Chinese/Japanese medicine?

Another paper has just been published using QPatch, showing that the Kampo medicine Mashiningan (MNG) improves opioid-induced constipation in rats by activating cystic fibrosis transmembrane conductance regulator. The effects were determined using QPatch.

To our knowledge this is one of the first papers on traditional Japanese/Chinese medicine-based on studies with a QPatch, which we find rather exciting.

For those of you who are not acquainted with Japanese Kampo, it is based on traditional Chinese medicine but adapted to Japanese culture. Kampo is widely practiced in Japan, and is fully integrated into the modern healthcare system.

You can read more about Kampo here and read more from the paper here

Ion channel blocking antibodies

Exciting work from Iontas. Concentration-dependent inhibition of Kv1.3 and ASIC1a currents were demonstrated using QPatch automated patch clamp.

Read more here

High throughput screening

Internal solution exchange on Qube 384 – New application report

Internal addition of compounds targeting the chloride channel CIC-1.

We demonstrate a robust ClC-1 assay on Qube with internal addition of compounds. The assay shows biophysical characteristics as expected for ClC-1 with good pharmacology and high Z-score. We further introduce Sophion`s Analyzer software that allows rapid analysis of large data sets to answer advanced electrophysiological questions, in the present case: What is the mode of action of a novel, unknown compound?

See the full application report here

Sophion in the US is moving to Boston

We are happy to announce that we will be moving our US facilities to Boston over the summer. The Boston offices and laboratory will, when finished, be fully operational for application and assay development, and as a training and demonstration laboratory for customers and development partners. Although our current laboratory in New Jersey was conveniently close to Manhattan and the Yankee Stadium, we have for the last couple of years wanted to move to Boston. The recent split from Biolin Scientific gave us that opening. Keep the line open and wait for the invitation for housewarming during the autumn.

QPatch automated patch clamp

New Nature paper on QPatch and neuronal stem cells

A group from University of Rostock has together with Sophion proved the feasibility of automated electrophysiological characterization of neuronal cells. The automated electrophysiology was done on a Sophion QPatch. With the QPatch’ unique ability to create gigaseals in physiological solutions the QPatch has again has shown its worth for advanced ephys measurements.

The QPatch data was done during a 6 weeks stay at Sophion as a part of Denise Franz Pd.D project. Congrats on the publication Denise, hope to see you again soon.

Read more here

Ion Channel Modulation Symposium 2017 – see the agenda

We are working with the final details for this years’ agenda and we are very proud of the line up. Again this year we have a good programme with excellent speakers and interesting topics.

You can see the agenda here.

 

 

Voltage- and current clamp on induced pluripotent cardiomyocytes with Qube 384

Action potentials are induced in both HL-1 mouse atrial cardiomyocytes and Axiogenesis Cor.4U iPS cell-derived cardiomyocytes.

Voltage- and current clamp on induced pluripotent cardiomyocytes with Qube 384. Action potentials are induced in both HL-1 mouse atrial cardiomyocytes and Axiogenesis Cor.4U iPS cell-derived cardiomyocytes. Qube can combine voltage clamp and current clamp in the same sweep for added experimental control. Click here to read more.

High throughput screening

Cav1.2 on Qube 384

For a long time, screening assays on CaV1.2 have been challenged by the tendency of CaV1.2 cell lines to exhibit declining current levels in the course of the experiment. Here we report a robust assay with high success rates and reliable pharmacology.

  • Success rates of 91% for Ca2+ currents and 98% for Ba2+ were achieved
  • Stable currents with as low as 0.6 ± 1.8% rundown per minute
  • Reference pharmacology in accordance with literature values
  • Use-dependent and use-independent mode of action distinguished with different voltage protocols

The voltage-sensitive L-type Ca2+-channel (LTCC) CaV1.2 is a crucial component for controlling intracellular activity and thereby essential in the cardiovascular and neuronal system. It is widely expressed in vascular smooth muscle tissue and the heart muscle 1-3. The opening of the channels leads to an increase of intracellular calcium, which act as second messenger, and thereby affects a variety of cellular processes 4 including heart muscle contraction and CaV1.2 is therefore an important target in e.g. safety pharmacology screening. CaV1.2 channels are known to require a large depolarization for their activation and once activated they display a long-lasting current flow, which typically can be blocked by low micromolar concentrations of e.g. dihydropyridines, phenylalkylamines and benzothiazepines 5,6.

In these studies, currents from HEK-hCaV1.2 were recorded on the high-throughput platform Qube 384 in both single-hole and multi-hole mode. Success rates, IV characteristics and the pharmacological effects of three different compounds were determined.