Did you miss our webinar novel patch clamp assays to advance pain research?

Don’t miss out on the valuable insights shared in last week’s webinar on the role of ion channels in pain signaling, particularly in the context of chronic pain conditions. Whether you missed it or want to rewatch it, the recorded webinar is now available for viewing.

First, Daniel Sauter, Scientific Sales Manager, Sophion Bioscience, Inc., gave an overview highlighting assays for typical pain targets recombinantly expressed in model cells and a concise introduction to the utilization of iPSC-derived DRG neurons in pain research. Reza Ghovanloo, a Neuroscientist at Yale School of Medicine, presented their groundbreaking study on recording currents from freshly isolated DRG neurons.

Click below to access the recorded webinar and learn more about Ion Channels in Pain.

New webinar in March – Novel patch clamp assays to advance pain research

In recent years, there has been a growing interest in the role of ion channels in pain signaling, particularly in the context of chronic pain conditions. Researchers have identified several ion channels involved in the sensation of pain, including the transient receptor potential (TRP) channels and the voltage-gated sodium channels (NaV). Understanding how these channels contribute to pain signaling is a key step in developing new and more effective pain therapies.
 

In this webinar, attendees will gain insight into the realm of automated patch clamp assays, exploring the mechanisms of pain. First, Daniel Sauter will offer an overview, highlighting assays for typical pain targets recombinantly expressed in model cells and a concise introduction to the utilization of iPSC-derived DRG neurons in pain research. Reza Ghovanloo will present a groundbreaking study on recording currents from freshly isolated DRG neurons.

ICMS® 2023 UK

We are happy to announce the dates for our next ICMS in Cambridge, UK.

Mark you calendar and keep an eye out for more information here.

Registration opens on 2 February, so click below to secure your seat.

Biophysics in coming up

Meet our ion channel experts at Biophysics this February. You can find us at booth #509 and get a demo on QPatch Compact, the latest member of our APC family.

Also, make sure to sign up for the annual Drug Discovery for Ion Channels XXIII, which takes place on Friday, February 17, in Room 8 at San Diego Convention Center.

Again this year, you are invited to our mini-symposium titled Electrophysiological Characterization of Cardiac Myocytes using Sophion Biosciences’ Automated patch Clamp Systems and the Intracellular Side of Axxam Electrophysiology. This meeting takes place on Tuesday, February 21, 11.30 AM – 1:00 PM in room 9 at San Diego Convention Center.

QPatch & Qube users have been busy in Q3, publishing 19 more publications

Here are some select highlights :

• Ghovanloo et al., PLoS ONE – in a collaboration between Simon Fraser University & Xenon Pharmaceuticals, used the Qube to define the effects of cannabidiol on gramicidin currents, & implications for their antibiotic activities.
• McMahon et al., Toxins; Wang et al., Membranes – the University of Queensland have two papers. McMahon et al. provide biophysical and pharmacological comparisons of marine snail conotoxins, SxIIIC, SmIIIA & KIIIA, blockers of Nav channels. Wang et al. investigated indole-3-carbinol, a natural product found in Brassica vegetables, their block of T-type calcium channels (Cav3.1-3.3) & roles in cancer anti-proliferation.
• Watt et al., JPTM – a thorough examination of cardiac ion channel safety pharmacology in hERG, Cav1.2, and Nav1.5 (peak/late), Dr Steve Jenkinson’s team at Pfizer compared GLP manual patch clamp data, Qube APC & hERG binding data, relating data to compound pro-arrhythmia/Torsades de pointes risk modelling.
• Wade et al., Bioconjugate Chem. – more snakebite antivenom antibody (nanobody) discovery & development in the 4^th publication arising from a fruitful collaboration between Prof. Andreas Laustsen’s lab at DTU & Sophion application scientist Dr Kim Boddum.

To see publications, click on the links below:

McMahon et al. (2022). µ-Conotoxins Targeting the Human Voltage-Gated Sodium Channel Subtype Nav1.7

Davie et al. (2022). A Potent and Selective Small Molecule Plasma Kallikrein Inhibitor Featuring a Novel P1 Group as a Potential Oral On-Demand Treatment for Hereditary Angioedema.

Toti et al. (2022). Structure−Activity Relationship and Neuroprotective Activity of 1,5-Dihydro-2H-naphtho[1,2-b][1,4]diazepine-2,4(3H)-diones as P2X4 Receptor Antagonists.

Sengupta et al. (2022). Novel benzoxazinone derivative as potent human neutrophil elastase inhibitor: Potential implications in lung injury.

Ghovanloo et al. (2022). Cannabidiol increases gramicidin current in human embryonic kidney cells: An observational study.

Caroff et al. (2022). Design, Synthesis, and Pharmacological Evaluation of Benzimidazolo-thiazoles as Potent CXCR3 Antagonists with Therapeutic Potential in Autoimmune Diseases

Wang et al. (2022). Diindolylmethane Derivatives: New Selective Blockers for T-Type Calcium Channels.

Gu et al. (2022). Targeting the LPA1 signaling pathway for fibrosis therapy: a patent review (2010-present).

Abram et al. (2022). Discovery of (R)‑N‑Benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [(R)-AS‑1], a Novel Orally Bioavailable EAAT2 Modulator with Druglike Properties and Potent Antiseizure Activity In Vivo.

Meyer et al. (2022). Discovery and In Vivo Evaluation of ACT-660602: A Potent and Selective Antagonist of the Chemokine Receptor CXCR3 for Autoimmune Diseases.

Watt et al. (2022). Use of high throughput ion channel profiling and statistical modeling to predict off-target arrhythmia risk – One pharma’s experience and perspective.

Jin et al. (2022). Development of fluorine-substituted NH2-biphenyl-diarylpyrimidines as highly potent non-nucleoside reverse transcriptase inhibitors: Boosting the safety and metabolic stability.

Faria et al. (2022). Environmental levels of carbaryl impair zebrafish larvae behaviour: The potential role of ADRA2B and HTR2B.

Wade et al. (2022). Generation of Multivalent Nanobody-Based Proteins with Improved Neutralization of Long α-Neurotoxins from Elapid Snakes. Bioconjugate Chemistry.

Zhang et al. (2022). Structure-Based Optimization of Coumestan Derivatives as Polyketide Synthase 13-Thioesterase(Pks13-TE) Inhibitors with Improved hERG Profiles for Mycobacterium tuberculosis Treatment.

Ma et al. (2022). Use of Solvent Mapping for Characterizing the Binding Site and for Predicting the Inhibition of the Human Ether-á-á-Go-Go-Related K + Channel.

Koester et al. (2022). Discovery of Novel Quinoline-Based Proteasome Inhibitors for Human African Trypanosomiasis (HAT).

Wang et al. (2022). Design, Synthesis, and Biological Evaluation of Androgen Receptor Degrading and Antagonizing Bifunctional Steroidal Analogs for the Treatment of Advanced Prostate Cancer.

Feng et al. (2022). Discovery of Selenium-Containing STING Agonists as Orally Available Antitumor Agents.

ICMS Cambridge 2022 revisited

Many of the delegates have attended all of the Sophion Ion Channel Modulation Symposia during the past five years.

In the below video, you can see why they keep coming back.

Nav1.5 screening in hiPSC-derived cardiomyocytes

Human induced pluripotent stem cells (hiPSC) hold much promise for advances in biomedical research (see our recent review here).

Sophion Bioscience has been leading the field in automated patch clamp recordings in hiPSC-derived cardiomyocytes (hiPSC-CMs – with a webinar on this here)

With developments in the Comprehensive in vitro Proarrhythmia Assay (CiPA) & the FDA Modernization Act calling for improved human model drug discovery assays and an increasing need to reduce animal testing, higher throughput cardiac ion channel assays in hiPSC-CM are in demand.

In our latest Application Report, Stefania Karatsiompani and Beatrice Badone developed a QPatch II automated patch clamp cardiac huNav1.5 ion channel screening assay on hiPSC-CM, made by collaborators iBET.

See these developments in cardiac ion channel safety pharmacology here.

New ion channel posters

You may remember our Cardiac Ion Channels poster we launched some time ago. We have now created two new posters for the collection – one about Ion Channels in Cancer and another about Ion Channels in Pain, and you can get your very own copy of the collection.

In return, we would only ask that you send us a picture of you in front of the posters, which we can share online.

Send us an email, and we will ship the posters to you.

We can’t wait to see some great photos of you/your colleagues in front of the posters.

New QPatch and Qube 384 publications in first half of 2022

45 new publications

The users of Sophion instruments – QPatch and Qube 384 – have had a very productive six months.

• Three papers on tuberculosis drug discovery, including work from the TB Drug Accelerator (TBDA), an extensive network of academic-industry labs.
• Nanyang Technical University (NTU) and A*STAR in Singapore, also with three papers e.g. a PNAS paper giving beautiful cryo-EM structures of Kv1.3 with/without bound peptide dalazatide.
• And three more papers from the shared, core APC facility in the University of Queensland on Nav channel pharmacology.

……and many more. Scroll through the list below and see them all.

Trovato et al. (2022). Cross clinical-experimental-computational qualification of in silico drug trials on human cardiac Purkinje cells for proarrhythmia risk prediction. Authorea Preprints, 1–25.

Johnson et al. (2022). NBI – 921352, a First-in-Class, Na V 1 . 6 Selective, Sodium Channel Inhibitor That Prevents Seizures in Scn8a Gain-of-Function Mice, and Wild-Type Mice and Rats. ELife.

Lao et al. (2022). Synthesis and biological evaluation of 1,2,4-triazole derivatives as potential Nrf2 activators for the treatment of cerebral ischemic injury. European Journal of Medicinal Chemistry, 236, 114315.

Lake et al. (2022). Neurotoxicity of an Hepatitis B Virus (HBV) Transcript Inhibitor in 13-Week Rat and Monkey Studies. Toxicological Sciences, 186(2), 298–308.

Yue et al. (2022). Novel potent azetidine-based compounds irreversibly inhibit Stat3 activation and induce antitumor response against human breast tumor growth in vivo. Cancer Letters, 534(February), 215613.

Miersch et al. (2022). Synthetic antibodies block receptor binding and current-inhibiting effects of α-cobratoxin from Naja kaouthia. Protein Science, 31(5), e4296.

Tran et al. (2022). Structural and functional insights into the inhibition of human voltage-gated sodium channels by μ-conotoxin KIIIA disulfide isomers. Journal of Biological Chemistry, 298(3), 101728.

Goggi et al. (2022). Imaging Kv1.3 Expressing Memory T Cells as a Marker of Immunotherapy Response. Cancers, 14(5), 1–12.

Taft et al. (2022). Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria. Journal of Medicinal Chemistry, 65(5), 3798–3813.

Ottavi et al. (2022). In Vitro and in Vivo Inhibition of the Mycobacterium tuberculosis Phosphopantetheinyl Transferase PptT by Amidinoureas. Journal of Medicinal Chemistry, 65(3), 1996–2022.

Pitsillou et al. (2022). Identification of novel bioactive compounds from Olea europaea by evaluation of chemical compounds in the OliveNet^TM library: in silico bioactivity and molecular modelling, and in vitro validation of hERG activity. Computers in Biology and Medicine, 142(January), 105247.

del Rosario et al. (2022). Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection. Nature Microbiology, 7(February).

DiMaggio et al. (2022). Anthracene-Walled Acyclic CB[n] Receptors: in vitro and in vivo Binding Properties toward Drugs of Abuse. ChemMedChem, 17(10), 1–10.

Lu et al. (2022). Discovery of Thieno[2,3- e]indazole Derivatives as Novel Oral Selective Estrogen Receptor Degraders with Highly Improved Antitumor Effect and Favorable Druggability. Journal of Medicinal Chemistry, 65(7), 5724–5750.

Huo et al. (2022). Discovery of pyrimidine-bridged CA-4 CBSIs for the treatment of cervical cancer in combination with cisplatin with significantly reduced nephrotoxicity. European Journal of Medicinal Chemistry, 235, 114271.

Kong, J., & Long, Y. Q. (2022). Recent advances in the discovery of protein tyrosine phosphatase SHP2 inhibitors. RSC Medicinal Chemistry, 13(3), 246–257.

Jiao et al. (2022). Design, Synthesis, and Evaluation of Benzoheterocyclic-Containing Derivatives as Novel HDAC1 Inhibitors. Pharmaceutical Fronts, 04(01), e22–e29.

Li et al. (2022). Structure-Activity Relationship Study of Indolin-5-yl-cyclopropanamine Derivatives as Selective Lysine Specific Demethylase 1 (LSD1) Inhibitors. Journal of Medicinal Chemistry, 65(5), 4335–4349.

Goggi et al. (2022). Imaging Kv1.3 expressing memory T cells as a marker of immunotherapy response. Cancers, 1–15.

Gold et al. (2022). Identification of β-Lactams Active against Mycobacterium tuberculosis by a Consortium of Pharmaceutical Companies and Academic Institutions. ACS Infectious Diseases, 8(3), 557–573.

Tyagi et al. (2022). Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug. Proceedings of the National Academy of Sciences, 119(5), 1–10.

Tanaka et al. (2022). Discovery of Brain-Penetrant Glucosylceramide Synthase Inhibitors with a Novel Pharmacophore. Journal of Medicinal Chemistry, 65(5), 4270–4290.

Ghovanloo et al. (2022). Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability. British Journal of Pharmacology, October 2021, 1–21.

Grychowska et al. (2022). Overcoming undesirable hERG affinity by incorporating fluorine atoms: A case of MAO-B inhibitors derived from 1 H-pyrrolo-[3,2-c]quinolines. European Journal of Medicinal Chemistry, 236.

Song et al. (2022). Discovery and Structural Optimization of Toddacoumalone Derivatives as Novel PDE4 Inhibitors for the Topical Treatment of Psoriasis. Journal of Medicinal Chemistry, 65(5), 4238–4254.

Faria et al. (2022). Environmental levels of carbaryl impair zebrafish larvae behaviour: The potential role of ADRA2B and HTR2B. Journal of Hazardous Materials, 431(February).

Dorado et al. (2022). Discovery and Evaluation of Novel Angular Fused Pyridoquinazolinonecarboxamides as RNA Polymerase I Inhibitors. ACS Medicinal Chemistry Letters, 13(4), 608–614.

Bell, D. C., & Dallas, M. L. (2021). Advancing Ion Channel Research with Automated Patch Clamp (APC) Electrophysiology Platforms. In L. Zhou (Ed.), Ion Channels in Biophysics and Physiology (pp. 21–32). Springer Singapore.

User Group Meeting – North America

Sophion Bioscience North America is thrilled to be hosting our in-person user meeting once again! We are excited to welcome all our users together to discuss the latest developments and best practices using the QPatch II and Qube 384 instrumentations. As well as introducing our newest instrument the QPatch Compact.

Topics will vary from techniques to use with iPSCs on automated patch-clamp instrumentation to cutting-edge new assays on a variety of channels.

This year’s meeting will future various speakers and a first look at our brand new facility in Bedford, MA. In between presentations there will be ample time to network and enjoy local brews and snacks.

Speakers include Kevin Sampson (Columbia University), Chris Hinckley (Biogen), Robert Brenner (UTHSCSA) and more.

Place:

Sophion Bioscience Inc. 312 Burlington Road,
Bedford, MA 01730

Nearest Hotels:

Hampton Inn

Homewood Suites

Residence Inn by Marriott

User Group Meeting – Europe

We are happy to invite you to our first in-person User Group Meeting in three years.

This year the meeting will be held at our premises in Copenhagen, and we are preparing a two-day event with a full-day scientific programme on day one and a hands-on workshop on day two, where you can get the chance to discuss with our ion channel experts and get a demo of our new QPatch Compact.

We plan to start at 9.00 AM on Thursday, September 8^th and wrap up just after lunch on Friday, September 9^th giving you the chance to spend the weekend in wonderful Copenhagen.

We currently have confirmed speakers from Metrion Biosciences, the Technical University of Copenhagen (DTU), Evotec, GSK and more. Stay posted for the agenda.

The Safety Pharmacology Society 2022 Annual Meeting

We’re happy to be back at the annual SPS meeting, which this year takes place in Montreal, Canada.

You can meet with experts on-site to hear more about how we can help your lab optimise your work with ion channels.

Drop by our booth no. 210 and get a demo of our new tabletop patch clamp system – QPatch Compact.

Read more about SPS here.

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.

Webinar: Automated Patch Clamping and iPSC Part II

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

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.

One requirement for improved preclinical data is a robust model system. Recent advances in stem cell technology have allowed for the creation of stem cells from patient skin or blood cells, called induced pluripotent stem cells (iPSCs). These patient-derived iPSCs can then be differentiated into neurons to model how a patient mutation causes changes in neuronal function compared with a healthy control neuron, followed by testing of therapeutics for reversal of these in vitro phenotypes. This strategy has already successfully transitioned from the bench to the clinic for amyotrophic lateral sclerosis (ALS). We have recently used this technology to better understand the cellular and molecular consequences of loss of CDKL5 in iPSC-derived neurons.

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.

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.

The NCCR TransCure Final Conference

Sophion is co-sponsoring this conference – NCCR TRansCure Final Conference – Excellence in Membrane Transport Research.

The meeting will take place in Bern, Switzerland from 17-19 August.

See the program here.

Ion channels and transporters: From molecule to human

We are excited to be co-sponsoring the EMBO/FEBS lecture course: Ion channels and transporters: from molecule to human.

This EMBO Practical Course provides an overview of the latest aspects of ion channel and transporter research. Topics covered include structural, functional and computational aspects, as well as more general themes, such as publishing and the role of women in science.

The meeting is taking place in Erice, Italy.

46th EWGCCE Meeting

This year we will be at the Annual Meeting of the ESC Working Group on Cardiac Cellular Electrophysiology.

We are joining more than 100 professionals specialized in the fields of cardiac ion channel physiology, excitation-contraction coupling, myocardial electrophysiology and related fields of cardiac physiology and pathophysiology.

See you in Toledo in June.

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:

Ion Channel Modulation Symposium 2022 (UK)

After two years of COVID lockdown, we can finally meet in person again, and there’s probably not a better opportunity to do this than at the Sophion Ion Channel Modulation.

This scientific meeting takes place at Clare College in beautiful Cambridge, the United Kingdom.

Read more about the symposium here where you can also see the agenda and register.

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.

Webinar coming up: APC and iPSC

We are happy to announce our next webinar taking place on March 15^th at 6 PM CET.

Human-induced pluripotent stem cells (hiPSC) offer much potential as inducible specialized model cells for biomedical studies and drug discovery.

In this webinar, Sophion Bioscience‘s Daniel Sauter will introduce hiPSC and their use on APC. This will lead to a collaboration with BrainXell, where Mike Hendrickson will present how they’ve used hiPSC in BrainXell’s CNS disease models and drug discovery.

We look forward to seeing you.

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:

Webinar coming up; APC & large molecules: a Venomtech/Charles River Laboratories venom toxin library screen

We are happy to invite you to our very first webinar in 2022.

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.

Drug Discovery for Ion Channels XXII – 2022 Satellite Meeting

This year’s meeting will highlight presentations from drug discovery companies, companies that provide ion channel services to drug discovery companies and companies that provide products to ion channel drug discovery companies, as well as other speakers in the field of ion channel drug discovery, including several academic speakers.

Please read much more about the meeting here

Please click here to register for the meeting. On-site registration will not be available, so please make sure to get your seat now.

Time:      Friday February 18 – 8:30 AM – 5:30 PM PST

Place:      Esplanade, Room 153, Moscone Center, San Francisco, CA

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.

Sophion at the forefront of cardiac ion channel electrophysiology

Cardiac ion channels are critical in the generation and maintenance of the cardiac action potential which drives the heartbeat. Consequently, cardiac ion channel safety assessment of new chemical entities (NCEs) for any new drug approval is a critical element of drug discovery.

In two recent publications, Sophion scientists have added to the cardiac ion channel field.

In collaboration with Toho University, Kazuya Tsurudome, Hironori Ohshiro and Taku Izumi, scientists from Sophion’s Tokyo labs, generated Qube data on the anti-atrial fibrillatory drug Oseltamivir against a panel of cardiac ion channels.

The second publication co-written by Damian Bell and Bernard Fermini, the highly experienced cardiac safety pharmacologist, was a review on automated patch clamp, the latest developments in functionality, how APC has been adopted and is changing cardiac safety assessment in drug discovery.

Both publications can be accessed here.

Read more about cardiac ion channels and Qube/QPatch here.

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 8-11^th (with preview days on 3^rd – 7^th).

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 (Na_V, K_V) 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.

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.

Tricky CRAC channels not so tricky on Qube and QPatch

Calcium release-activated calcium (CRAC) ion channel currents (ICRAC) are critical in many diseases. Compounds modulating ICRAC have been developed towards treatment for autoimmunity (e.g. rheumatoid arthritis, multiple sclerosis, diabetes, inflammatory bowel disease, psoriasis, mast cell-related disorders), metastatic breast cancer, cardiovascular and cerebrovascular diseases and viral infections, and may help to prevent transplant rejection.

One of the most advanced CRAC drug discovery programmes has been performed by CalciMedica, with their Auxora compound in clinical trials for diseases as diverse as pancreatitis & Covid-19.

The ability to efficiently record these channels on automated patch clamp (APC) would be advantageous. However, some APC platforms struggle to make recordings without ‘seal enhancer’ solutions containing high calcium and fluoride, both ions cause problems recording ICRAC.

Addressing this tricky channel on APC, Sophion’s scientists have successfully recorded ICRAC on QPatch and Qube without the need for problematic calcium or fluoride.

For more info & publications on CRAC channels and efficient APC recordings, click here.

TRP channels, Nobel prizes and Automated Patch Clamp

The breakthrough discoveries in this year’s Nobel Prize laureates for physiology or medicine enable us to understand how heat, cold and mechanical forces can initiate the nerve impulses that allow us to perceive and adapt to the world around us. Read more about this year’s laureates here.

At Sophion, we are excited that the prize again this year goes to laureates working in the field of ion channels.

TRP channels are critical for our ability to perceive temperature and also play important roles in nociception, including neuropathic &  inflammatory pain pathways. The Piezo channels endow us with the sense of touch and the ability to feel the position and movement of our body parts (proprioception).

Of course, we have worked on these ion channels for years. While our research at Sophion does not qualify for a Nobel prize (at least not yet), nonetheless, we are proud that our systems contribute to the further understanding of the functionality of these vital membrane proteins.

In honour of this year’s laureates and for those of you that would like to learn more about TRP channels, we have gathered some TRP-themed videos from previous Sophion ICMS symposia for you to watch over morning coffee. If you want to learn even more, check out the list of peer-reviewed publications, application reports and posters below.

As always, if interested in setting up new assays on your QPatch II or Qube 384 or optimizing your existing assay, we recommend discussing this with your dedicated (soon to be laureated?) Application Scientist.

Publications

• Barilli A, Aldegheri L, Bianchi F, Brault L, Brodbeck D, Castelletti L, et al. From High-Throughput Screening to Target Validation: Benzo[d]isothiazoles as Potent and Selective Agonists of Human Transient Receptor Potential Cation Channel Subfamily M Member 5 Possessing In Vivo Gastrointestinal Prokinetic Activity in Rodents. J Med Chem [Internet]. 2021 May 13 [cited 2021 Jul 6];64(9):5931–55. LINK
• Damann N, Bahrenberg G, Stockhausen H, Habermann CJ, Lesch B, Frank-Foltyn R, et al. In vitro characterization of the thermoneutral transient receptor potential vanilloid-1 (TRPV1) inhibitor GRTE16523. Eur J Pharmacol [Internet]. 2020;871:172934.
• McPate M, Bhalay G, Beckett M, Fairbrother S, Gosling M, Groot-Kormelink PJ, et al. The development of automated patch clamp assays for canonical transient receptor potential channels TRPC3, 6, and 7. Assay Drug Dev Technol. 2014 Jun;12(5):282–92.
• Sunesen M, Jacobsen RB. Study of TRP Channels by Automated Patch Clamp Systems. In: Islam MS, editor. Transient Receptor Potential Channels [Internet]. Dordrecht: Springer Netherlands; 2011. p. 107–23.

Application reports and posters

• Jensen 2008. TRPM8 tested on QPatch. Sophion Application Report.
• Jacobsen et al., 2011. TRPV1 tested on QPatch. Sophion Application Report.
• Jensen 2012. TRPM8 cold-sensitive ion channels tested on QPatch. Sophion Application Report
• Jacobsen et al. 2010 TRP’ing in multi-hole mode. Poster Biophysics 2010.
• Chakrabarti et al., 2019. In vitro inflammatory knee pain: Of Mice and Men.

Sophion ICMS talks:

• TRPC1 as a negative regulator for TRPC4 and TRPC5 channels. Professor Insuk So, Seoul National University, Korea. ICMS 2019 Cambridge UK.
• Structural basis for pharmacological modulation of the TRPC6 channel elucidated by cryo-EM. Dr Yonghong Bai, Amgen. ICMS 2019, Boston, USA.
• Redox biology of TRP channels. Professor Yasuo Mori, Kyoto University, Japan. ICMS 2018 Cambridge UK.
• Piezo1 channel function and small-molecule modulation. Professor David Beech, Leeds University, UK. ICMS 2018 Cambridge UK.

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:

Sophion Academy – how-to video tutorials

Whilst we far prefer to see and support our users in person, sometimes for both you and us it’s easier, more efficient & practical to point you in the direction of our excellent video tutorials. These tutorials cover many aspects of the most common aspects of maintenance and data analysis.

Unlike our application scientists and field service engineers that need to rest – they’re good, pretty close to super-human, but even they need to sleep occasionally – these handy tutorials will always be at your side 24/7/365.

So, whether you need to clean your bed-of-nails, save a debug file for us to do a deeper dive into your APC’s performance and data or brush up on your data analyses like grouped Hill fits in Sophion Analyzer, we’ve got you covered.

See more video tutorials here, where you can also see our services for additional courses and training:

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.

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.

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.

Ion Channels and Cancer

Ion channels are critical signaling proteins in all of the main hallmarks of cancer – see image above. Indeed, Prof. Saverio Gentile of the University of Illinois, Chicago, has pithily defined this inextricable connection as ‘a channelopathy called cancer’.

Sophion are at the forefront of ion channel research supporting and collaborating with world-leading oncochannelopathy labs, including hosting presentations on their findings at our Ion Channel Modulation Symposia, User Meetings & webinars.

Links to recordings of these lectures are given below.

Ion Channels and Cancer

Prof. Annarosa Archangeli, ICMS 2017, ‘hERG Channels: From anti-targets to novel targets for cancer therapy’

Dr Luis Pardo, ICMS 2017, ‘Kv10.1 and the cell cycle: A two-way road’

Prof. Mustafa Djamgoz, ICMS 2019, ‘In vivo evidence for expression of voltage-gated sodium channels in cancer and potentiation of metastasis’

Prof. Saverio Gentile, User Meeting 2021, ‘Targeting potassium channels in cancer from cell signaling to precision medicine

Safety Pharmacology Society – Annual Meeting 2021 (virtual)

For the second year in a row, SPS will be virtual. Sophion will be having a virtual booth again. Read about the meeting here.

Stay tuned for more information.

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

Sophion User Meeting – Virtual (Europe)

You are invited to the annual Sophion User Meeting, which will be a virtual one. We had hoped that it would be possible to finally meet in person again this autumn for the traditional User Meeting in Europe. Still, we acknowledge that many of you don’t know if you can travel yet due to company policies or are concerned about the COVID-19 situation in general.

Even though we initially planned it as a European meeting, everyone is welcome. So virtual meetings aren’t always for the worse.

Speakers:

• Eddy Stevens from Metrion Biosciences
  Title: Development of a QPatch current-clamp assay as a physiologically relevant screen for Kv1.3 inhibitors
• Juha Kammonen from Charles River Labs
• David Penton Ribas from the University of Zürich
  Title: Automated patch clamp in academic research. Challenges and opportunities
  
• Mads P. G. Korsgaard, Product Manager – Qube 384
  Title: News & updates on Sophion instruments
• Thomas Binzer, VP R&D and Marketing
  Title: Sophion Management Update

We have more speakers in the pipeline.

Stay tuned.

We reserve the right to turn down any registrant.

Q2 sees a bumper crop of 15 publications using Qube 384 and QPatch

Q2’s bumper crop of papers is a nice mix of industry & academic institutions – see the list of contributing labs below. The 15 publications cover a broad range of ion channels (P2X7, hERG, NMDAR, nicotinic acetyl choline receptors, TRPM5, Kv7.2/7.3) & research (Alzheimer’s, multiple sclerosis, cancer, schizophrenia, amnesia, chronic pain, diabetes, anti-bacterials, epilepsy).

Two of the publications were Sophion authored on cardiac ion channel pharmacology. In collaboration with Toho University, Tokyo, Kazuya Tsurudome, Hironori Ohshiro & Taku Izumi studied the anti-atrial fibrillation drug Oseltamivir. A second publication written by Damian Bell & Bernard Fermini – one of the godfathers of cardiac safety pharmacology – is a wide-ranging review on APC in safety assessment.

Finally, what quarter would be complete without yet more great research emanating from the publishing machine that is the University of Queensland.

In Jiang et al., Glenn King’s lab have published on a tarantula toxin that blocks Nav1.7 ion channels, showing its ability to reduce chronic visceral pain in irritable bowel syndrome (IBS).

Jensen et al., another paper involving the King lab in collaboration with Jennifer Deuis, Irina Vetter & Samuel Robinson’s labs, have done a deep dive into the venomous peptides of the velvet ant.

Congratulations to all labs publishing this quarter including: Yale, Stanford, University of Utah, Lundbeck, Gedeon Richter, Orion Pharma, Boehringer Ingelheim, Peking University, Guizhou University, ESTEVE, Barcelona Institute of Science & Technology, Aptuit, Takeda, Novartis, Linköping University, University of Chinese Academy of Sciences.

Here you can see all the latest publications:

Kambayashi et al., 2021 Translational Studies on Anti-Atrial Fibrillatory Action of Oseltamivir by its in vivo and in vitro Electropharmacological Analyses

Jensen et al, 2021 Venom chemistry underlying the painful stings of velvet ants (Hymenoptera: Mutillidae)

Hopper et al., 2021 Synthesis and Characterization of the Novel Rodent-Active and CNS-Penetrant P2X7 Receptor Antagonist Lu AF27139

Bell, D.C. & Fermini, B., 2021 Use of automated patch clamp in cardiac safety assessment: past, present and future perspectives

Li et al., 2021 Identification of poly(ADP-ribose)polymerase 1 and 2 (PARP1/2) as targets of andrographolide using an integrated chemical biology approach

Schuelert et al., 2021 The Glycine Transport Inhibitor Bi 425809 Restores Translatable EEG Deficits in an Acute Mouse Model for Schizophrenia-Related Sensory Processing and Cortical Network Dysfunction

Paradkar et al., 2021 Creation of a new class of radiosensitizers for glioblastoma based on the mibefradil pharmacophore

Ledneczki et al., 2021 HTS-based discovery and optimization of novel positive allosteric modulators of the α7 nicotinic acetylcholine receptor

Díaz et al., 2021 Tricyclic Triazoles as σ1Receptor Antagonists for Treating Pain

Barilli et al., 2021 From High-Throughput Screening to Target Validation: Benzo[d]isothiazoles as Potent and Selective Agonists of Human Transient Receptor Potential Cation Channel Subfamily M Member 5 Possessing In Vivo Gastrointestinal Prokinetic Activity in Rodents

Lapointe et al., 2021 Discovery and Optimization of DNA Gyrase and Topoisomerase IV Inhibitors with Potent Activity against Fluoroquinolone-Resistant Gram-Positive Bacteria.

Ottosson et al., 2021 Synthetic resin acid derivatives selectively open the hKV7.2/7.3 channel and prevent epileptic seizures.

Kong et al., 2021 Design, Synthesis, and Biological Evaluation of Novel Pyrimido[4,5-b]indole Derivatives Against Gram-Negative Multidrug-Resistant Pathogens

Jiang et al., 2021 Pharmacological Inhibition of the Voltage-Gated Sodium Channel NaV1.7 Alleviates Chronic Visceral Pain in a Rodent Model of Irritable Bowel Syndrome

Zheng et al., 2021 Discovery of Methylene Thioacetal-Incorporated α-RgIA Analogues as Potent and Stable Antagonists of the Human α9α10 Nicotinic Acetylcholine Receptor for the Treatment of Neuropathic Pain

74th Annual Meeting of the Society of General Physiologists

We are happy to be co-sponsoring the 74th Annual Meeting of the Society of General Physiologists themed Ion Channels & Transporters in Immunity, Inflammation &
Antitumor Immunity.

The 74th Annual Meeting of the Society of General Physiologist will be the first international conference fully dedicated to the topic of Ion Channels and Transporters (ICTs) in the immune system. This meeting will provide a unique opportunity for immunologists and ion channel physiologists to discuss latest advances in the regulation, function and physiological roles of ion channels in innate and adaptive immunity.

The meeting will take place in September at Marine Biological Laboratory in Woods Hole, MA, the United States and it’s possible to attend both online as well as in person.

Find out more about registration here.

71st National Congress of The Italian Society of Physiology

We are happy to be co-sponsoring the 71st National Congress of The Italian Society of Physiology. This event will be virtual.

Our very own Beatrice Badone will give a talk on 7th September at 16.30 (Hall D). Beatrice will present Sophion’s data on High throughput screening using QPatch II and Qube 384 systems: electrophysiological evaluation of primary neurons, glial cells and hiPSC-derived motor neurons.

Abstract:

The QPatch II and Qube 384 are two automated patch-clamp (APC) systems useful for evaluating the electrophysiological properties of different cell models, with the possibility to perform high throughput compound screening for drug discovery. These systems provide high fidelity recordings which, in combination with accurate, low volume applications, make them ideal for studying both voltage- and ligand-gated ion channels. With a rapidly increasing number of ion channels identified as potential therapeutic targets in neurological diseases, there is an urgency of finding valid neuronal cell models. Among these, primary brain cells and human-induced pluripotent stem cells (hiPSCs)-derived neurons are promising physiological models for evaluating ion channels properties and potential drugs. Here we used our APC systems for studying both voltage-gated (Na, K ) and ligand-gated (GABA ) 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. Patch-clamp recordings require healthy membranes for high resistance sealing; however, different isolation methods may alter the membrane composition and change intracellular characteristics. Here we demonstrate that the electrophysiological properties of both brain cell models are maintained during APC recordings, confirming that both QPatch II and Qube 384 are powerful platforms for investigating brain cell models.

You can read much more about the event here.

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.

Sophion Virtual User Meeting – North America

With the continually evolving Coronavirus situation the Sophion North America team has made the decision to host our October 13th, 2021 User Meeting entirely virtually. While this does mean no Lord Hobo beer tasting this year, we are still very excited to see all of our wonderful users virtually and to hear presentations from our group of distinguished speakers.

When: 11 AM ET October 13th

Where: Online

Speakers:

If you have any questions please reach out to ski@sophion.com

Sophion is committed to following the CDC’s guidance regarding the COVID-19 pandemic and will encourage social distancing and mask-wearing whenever necessary.

Sophion User Meeting – Japan

Stay tuned for more information about the virtual User Meeting in Japan 10th September 2021.

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):

SLAS2022

Meet us at SLAS2022 at Boston Convention and Exhibition Center. You can find us in booth #1548.

Make sure to drop by our booth  – we are bringing our brand new semi-automated patch clamp system, QPatch Compact, for demos.

Poster presentation:

Tuesday, 8th February – 5:00 PM – 6:00 PM

1088-D: Characterization of the rapidly-desensitizing α7 nicotinic acetylcholine receptor using the Qube (click here to see the abstract)

Weifeng Yu, PhD – Director, SOPHION BIOSCIENCE

Exhibition hours are:

Monday 7th February 10:00 AM – 7:00 PM
Tuesday 8th February 10:00 AM – 7:00 PM
Wednesday 9th February 10.30 AM – 1:30 PM

Biophysics 2022

We will be at the 66th Biophysical Society Annual Meeting meeting in 2022.

Meet our ion channel team at booth #519 from Sunday  to Tuesday (20th to 22nd February) where we will showcase our brand new QPatch Compact – a semi-automated patch clamp system.

You can also try to do a bit of virtually automated patch clamping in our VR Sophion universe at the booth.

Monday February 21st

Poster presentation at 1:45 PM – poster board no. B449 – Presenter: Mei Zhang

Title: Using automated patch clamp for high throughput characterization of sodium and potassium channels in human induced pluripotent stem cell-derived sensory neurons

Tuesday February 22nd

Poster presentation at 1:45 PM – poster board no. LB65 – Presenter: Application Scientist Mei Zhang

Title: Electrophysiological characterization of human iPSC-derived cardiomyocytes in physiological solutions using QPatch II, including measurements of ik1 and compound effects on paced action potentials

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.

SLAS Annual Meeting 2022

You can find us at booth #1548 at the 2022 SLAS International Conference and Exhibition. We look forward to finally seeing you in person.

The conference will take place at the Boston Convention and Exhibition Center, MA.

Neuroscience 2021 – Virtual Meeting

Neuroscience 2021 will take place online November 8-11, 2021

For more information about the meeting, click here

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 V_½) have been expanded to V_xx so you can manipulate the channels into precisely the state you find relevant. The individual V_xx can be used both to stimulate and as V_hold. 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 Ca_V2.2 & Na_V1.7 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 6^th 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.

Texas Pain Research Highlights 2021

We are happy to be part of the Texas Pain Research Highlights 2021 meeting that takes place on April 7th and 8th.

You can meet us in our virtual booth where it will be possible to chat with our ion channel experts. More information will follow shortly.

On April 8, 12:35 – 1:15 PM CST, Dr Daniel Sauter, Scientific Sales Manager will be presenting a poster titled:

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

In the meantime, you can read relevant publications, papers, reports and posters on ion channels in pain right here.

Webinar: Automated Patch Clamping in CROs – How APC is advancing cardiac safety assessment

In this webinar, Sophion’s Dr Anders Lindqvist will give an introduction to how APCs have revolutionised our capabilities to efficiently determine cardiac safety liabilities & how the latest advances in APC technology are making tomorrow’s drugs safer.

Our guest speaker will be Dr Michael Morton of ApconiX, a CRO that specialises in drug toxicology & safety assessment. Dr Morton will present examples of cardiac ion channel safety pharmacology studies showcasing the development of APC technologies & where the latest technology will take our drug discovery efforts.

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.

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

The K_v1.5 channel is found in many tissues and is the molecular background behind I_kur 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.

Webinar: Automated Patch Clamp in Academia Part II

The role of ion channels as promising pharmacological targets in oncology is well-documented. Ion channel inhibition has the potential to reduce proliferation, migration and invasion of cancer cells, as well as block tumour angiogenesis pathways. In the last decade, our understanding of ion channel function in carcinogenesis has dramatically accelerated due to Automated Patch Clamping and will continue to be a key focus of future research in the ion channel field. Although further work is needed to fully understand ion channel function in carcinogenesis and possible side effects, it is an exciting and emerging area of research in the ion channel field.

In this webinar, we will provide a brief overview of the ion channels of interest in oncology and Dr Aamir Ahmed from King’s College London will discuss his work using QPatch for the investigations of the overlap between ion channels, wnt-signalling and intracellular calcium release in cancer cells. Aamir will be followed by application scientist, Naja Møller Sørensen, from Sophion who will give a short presentation about ion channels and cancer

BPS2021 65th Biophysical Annual Meeting

Biophysics 2021 will be virtual. Sophion will be attending as usual but with a virtual booth.

Read more about the meeting here. More information about the annual satellite meeting: Drug Discovery in Ion Channels will follow shortly, so stay posted.

SfN Global Connectome – a virtual event

Neuroscience, which was planned for late October 2020, was cancelled due to the global pandemic situation.

SfN has now organised the SfN Global Connectome virtual event instead and Sophion will be part of this event with a virtual booth. At our booth you can meet with Daniel Sauter, Scientific Sales Manager and Gus Fish, Sales Account Manager, both from Sophion Bioscience, North America.

Dr Weifeng Yu, Senior Application Scientist with Sophion Bioscience, North America will be presenting a poster titled:

“Evaluation of positive allosteric modulators of SK2 channels using QPatch”

Abstract:

Small-conductance Ca²⁺-activated K+ (SK) channels mediate afterhyperpolarization in neurons and dampen the firing frequency of action potentials. Calmodulin is constitutively associated with the SK2 channels and serves as the Ca²⁺ sensor for the SK-calmodulin complex. The SK2 channel subtype plays a key role in the regulation of excitability of Purkinje cells in the cerebellum. Given their importance in Purkinje cells, SK2 channels are a promising drug target for ataxia, a movement disorder.

Automated patch clamp (APC) machines, such as QPatch, have been used in the pharmaceutical industry to study drug interaction with varieties of ion channels. Over the past decade, the technology has contributed significantly to pharmaceutical research and drug discovery. Here, we report to use QPatch as a tool for testing and evaluating the positive allosteric modulators of SK2 channels. A stable cell line of the rat SK2 channel tagged with GFP was established through transfection of HEK293 cells followed by puromycin selection and enrichment using repeated GFP fluorescence-activated cell sorting.

Positive allosteric modulators were tested under whole-cell voltage-clamp configuration with automated QPatch. The compounds that positively modulate the SK2 channels in the automated QPatch was further tested with the inside-out patch manual recordings. The results from automated whole-cell recordings and inside-out patch manual recordings were consistent.

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 3^rd 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 K_v1.5 channel is found in many tissues and is the molecular background behind I_kur 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 Ca_v1.2. 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.

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, Na_V1.1 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.

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.

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.

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, Na_V1.1 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

On 5^th 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.

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, Na_V1.7, 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 5^th 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

Ca_V1.2 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 Ca_V1.2 on the QPatch, we regularly achieve success rates of >85%, however rundown can be high in some Ca_V1.2 assays, something that makes it inherently difficult. We tested a new Ca_V1.2 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 Ca_V1.2 assay on Qube 384 and QPatch here.

If you have issues with rundown in your Ca_V1.2 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 5^th 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 V^½ reduces data variability compared to traditional standard methods and that commercialized drugs with state-dependent effects were successfully detected by V^½ 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 Na_v1.7 on a Qube automated patch‐clamp system. Three protocols along with step‐by‐step details are provided. First, we describe a protocol to estimate V_½, 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 V_½ 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 Na_v1.7.

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.

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., 2019. Enzymatic 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., 2019. Validation 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 V_half values and reliable potentiation of Kv7.3/7.2 currents on Qube 384
 
Rosholm 2019. Electrophysiological 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.

CANCELLED: Ion Channel Modulation Symposium, Cambridge, UK

We regret to inform that due to COVID-19, the 5^th Ion Channel Modulation Symposium in Cambridge, United Kingdom, has been cancelled.

It hardly comes as a surprise that we, due to the severe situation caused by the COVID-19 pandemic, have to cancel the 5^th 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

2^nd and 3^rd June 2021

We look forward to seeing everyone in 2021.

See here why you should attend the ICMS:

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, Na_V1.1 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

SLAS 2020

You can meet us at SLAS 2020 from 27th to 29th January at the San Diego Convention Center.

From the Sophion team, you can meet our ion channels team Katherine Webster, President NA, Gus Fish, Sales Manager NA, Daniel Sauter, Application Scientist NA and Rasmus B Jacobsen, Application Development Manager.

Send us an email if you want to arrange a meeting with us or if you wish to have a demo on our high-throughput, automated patch clamp system, Qube 348 that we are showcasing.

Tuesday, 28 January

Poster presentation:

Title: Development of an Automated Patch Clamp Assay for recording STIM1/Orai1 – mediated currents using Qube 384

Presented by application scientist Daniel R Sauter

Time: 2:00 PM to 3:00 PM

Poster No.: 1287-C

Read more about SLAS2020 here.

Stable Kv7.2/7.3 current on Qube

The heteromer K_v7.2/7.3 underlying the M-current was recorded in Qube. With high success rates, we saw stable V_½ 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.

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.

ICMS 2019, Boston, MA

We are thrilled to announce the dates for the very first US-based Ion Channel Modulation Symposium and look forward to seeing many ion channel professionals in October in Cambridge, MA (USA). Sophion has joined forces with Amgen and together we will host a two-day event packed with great talks and excellent networking opportunities.

The meeting will be held at the Royal Sonesta Hotel in Cambridge, MA.

See much more information about this meeting 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 assay created by Metrion: Nav1.5(Late) cardiac safety on QPatch

Using the QPatch, Metrion has created and validated a Na_V1.5(late) assay that removes the requirement for pharmacological enhancers of Na_V1.5(Late) and, thereby, delivers improved cardiac safety screening reliability and cost. Read the report here.

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

If you didn’t receive our latest newsletter you can read it by clicking here.

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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 Na_V1.1 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.

Neuroscience 2019

This years’ SfN conference will take place in Chicago. Please drop by our booth #1608 and have an ion channel talk with our specialists.

We will keep you updated. In the meantime, you can read more about the meeting here.

Safety Pharmacology Society – annual meeting

We look forward to seeing you in Barcelona for this years’ SPS. You can meet our dedicated ion channel experts at our booth #501.

Meeting Location:

Centre de Convencions Internacional de Barcelona
Plaça de Willy Brandt, 11–14
08019 Barcelona, Spain

More information about our activities at SPS will follow. Read more about SPS here.

Sophion User Meeting – Japan

Please mark your calendars. We are planning the Sophion User Meeting in Japan.

Venue:

Knowledge Capital Conference Rooms, Room C04
Grand Front Osaka, North Bild., Tower C, 8F
3-1 Ofuka-cho, Kita-ku, Osaka 530-0011, Japan

Click here to see the agenda in English and in Japanese

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 (Na_V1.1-8). 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.

SOT 58th Annual Meeting & ToxExpo

This year will will be at the SOT ToxExpo which takes place in Baltimore Convention Center. Make sure to come at see us at our booth #4298 and get a demo of our brand new QPatch II.

We look forward to see you in Baltimore – read more about SOT ToxExpo here.

Cav1.2 on Qube, no rundown

High success rates and minimal rundown with pharmacology according to literature values. The third Ca_V1.2 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.

Sophion User Meeting, Boston 2019

We look forward to seeing you again this year for our Sophion User Meeting in Boston.

Venue:

Hilton Boston/Woburn, 2 Forbes Rd. Woburn, MA 01801

Agenda:

April 9

11:30 AM          Registration and lunch buffet

01:00 PM          Novel small molecule Nav channel blockers selectively targeting nociceptors
Dr Xiaguang Victor Chen, Nocion

01:30 PM          KnotBodies: an efficient platform to generate ion channel modulating antibodies by fusing venom-derived knottins into antibody CDR loops
Dr Damian Bell, Iontas

02:00 PM          Utilising the Qube in a CRO environment: Case studies from HTS and hit-to-lead projects
Dr Abigail Marklew, Charles River Laboratories

02:30 PM          Coffee break

03:30 PM          IPSC-Derived Human Neurons for Disease Modeling and Drug Discovery
Dr Mike Hendrickson, BrainXell

04:00 PM          Expanding ion channel assay capabilities using high-performance cell engineering
Dr Joan Foster, MaxCyte

04:30 PM          Qube update – version Eagle, motor neurons and adaptive protocols
Dr. Mads P G Korsgaard, Sophion Bioscience A/S

05:00 PM          Dinner

April 10

08:00 AM          Coffee

09:00 AM          Profiling sodium channels to improve drug candidate safety and efficacy using the
QPatch HT
Dr Bryan Koci, Eurofins

09:30 AM          Inhibitory effects of cannabidiol on voltage-dependent sodium currents
Dr Reza Ghovanloo, Simon Fraser University and Xenon Pharmaceuticals

10:00 AM          Coffee break

10:30 AM        Impact of equilibrium om interpretation of hERG QPatch data
Dr Anatoli Lvov, Novartis

11:00 AM          QPatch II – The next generation QPatch
Dr Göran Mattsson, Sophion Bioscience A/S

11:30 AM          Lunch at the hotel

01:00 PM          Open house at Sophion Bioscience, Inc.

05:00 PM          Wrap-up

Our sponsors:

Gold sponsor:

Silver sponsor:

Local hotels:

Hilton Boston/Woburn
2 Forbes Road, Woburn, MA
Phone: +1 781-932-0999

Crowne Plaza Boston/Woburn
15 Middlesex Canal Park Drive, Woburn, MA
Phone: +1 781-935-8760

Comfort Inn Boston/Woburn
14 Hill St, Woburn, MA 01801
Phone: +1 781-933-5363

Sophion User Meeting, Copenhagen 2019

We look forward to seeing you for the annual European Sophion User Meeting. This year the meeting will be held at our premises in Copenhagen, and we are preparing a two-day event with a full-day scientific programme on day 1 and a hands-on workshop on day two, where you can get the chance to discuss with our ion channel experts.

We plan to start around 9.00 AM on Thursday, September 5th and wrap up just after lunch on Friday, September 6th giving you the chance to spend the weekend in wonderful Copenhagen.

The user meeting is kindly sponsored by:

5th September 2019

09.00     Registration – tea/coffee

09.15     Welcome remarks
Thais Johansen, Sophion Bioscience A/S

09.30     P2X3 and P2X2/3: The hare and the tortoise….
Jean Francois Rolland, Axxam SpA

10.00     Strategies for reducing attrition in early drug discovery
David Downie, GSK

10.30     Tea/coffee

11.00     NDMA assays on the Qube system
Abigail Marklew, Charles River Labs

11.30    QPatch HTX assay development for TRPM5 channel to successfully identify potentiators and blockers
Caterina Virginio, Aptuit (Evotec)

12.00    Potency determination of positive Nav1.1 modulators  measured on QPatch II
Julie Klint, Lundbeck

12.30     Lunch

13.30    TMEM16A potentiation: a novel therapeutic approach for the treatment of cystic fibrosis
Sarah Lilley, Enterprise Therapeutics

14.00    Resin-acid derivatives as hKv7.2/7.3 channel openers
Nina Ottosson, Lindköping University

14.30     Recent drug discovery applications run on QPatch in CRO collaborative mode
Edward Humphries, Metrion Biosciences

15.00     Tea/coffee

15.30     Update on QPatch II
Göran Mattsson, Sophion Bioscience A/S

15.50     Update on Qube; adaptive protocols and more…..
Mads P G Korsgaard, Sophion Bioscience A/S

16.10     Sophion developments projects update
Sandra Wilson, Sophion Bioscience A/S

16.30     Wrap up
17.00     Transport to the evening event
18.00     Dinner at Færgen Ellen / Kontiki Bar

6th September 2019

09.00    Tea/coffee
09.30    Workshop day is a day dedicated the user where we will touch base with the below issues:

• Adaptive voltage protocols NEW FEATURE!
• Temperature control, new feature on QPatch II coming up!
• Custommade protocols
• Advanced analysis – bring your own assays
• Tips and tricks for cultivating cells
• Learn about the daily cleaning procedure of your APC system

If you have other issues you’d like to hear about please let us know. Drop us an email.

13.00    Lunch
Wrap up

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:

• Pfizer (Donglin et al): Simultaneous Measurement of Cardiac Na_V1.5 Peak and Late Currents in an Automated QPatch Platform
• Pfizer (Donglin et al): Simultaneous Measurement of Cardiac hERG and Na_V1.5 Currents Using an Automated Qube^® Patch Clamp Platform
• Metrion Biosciences (Humphries et al): New CiPA cardiac ion channel cell lines and assays for in vitro proarrhythmia risk assessment
• Eurofins (Koci et al): Optimization of Cardiac CiPA Targets (hCa_V1.2 and hKCNQ1/hminK) on the QPatch HT Automated System
• Eurofins (Renganathan et al): Automated High Throughput Na+ Late Current Assay on QPatch HT Platform for CiPA28
• Sophion Bioscience (Lindqvist et al): Estimating hERG drug binding using temperature-controlled high throughput automated patch clamp

Kv7 Channels Symposium 2019

We are happy to be taking part in this symposium which will provide comprehensive insight into the myriad aspects of Kv7 research almost 25 years after the first KCNQ gene was identified.

The symposium will be hosted at the University of Naples Federico II in the beautiful surroundings of the bay of Naples, Italy.

Read more about the Kv7 Channels Symposium here.

See you in sunny Naples in September.

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.

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.

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.

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

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

Biophysical Society 63rd Annual Meeting 2019

As always at Biophysics we have a lot of activities going on. Please see below.

Friday, 1st March

Ion Channel Satellite Meeting

Sophion will be co-hosting the recurring satellite meeting, Drug Discovery for Ion Channels. Read more about the meeting here.

Saturday, 2nd March

Customer outing

Monday, 4th March

01:45 PM – Poster presentation:

Title: IPSC-derived motor neurons on the automated patch clamp platforms Qube and QPatch

Poster presenter: Application scientist Kadla Rosholm

Location: Exhibit Hall A-E – Poster board No.: B332

Abstract:

Human induced pluripotent stem cells (hiPSCs) can be differentiated into multiple cell types, including neurons and cardiomyocytes. This gives rise to a novel way of establishing human disease models, which in turn can be used for drug development in vitro. Ion channels represent highly attractive therapeutic targets in the nervous and the cardiovascular system, rendering electrophysiological studies of hiPSCs important for their usage in drug discovery. However, such studies have traditionally been limited by the labor-intensive and low-throughput nature of patch-clamp electrophysiology. Here we use our automated patch clamp systems Qube 384 and QPatch 48 in order to increase throughput and reduce timelines.
Our observations include channel expression versus time in culture, the pharmacological dissection of endogenous ion channels (e.g. Nav and Kv), identification of ligand-gated receptors, and recordings of action potentials using the current clamp feature. Also, we show the electrophysiology of a spinal muscular atrophy (SMA) and an amyotrophic lateral sclerosis (ALS) model. The disease model for SMA was derived by mutations in the SMN1 gene and shows enhanced sodium channel activity but no shift in the normalized current-voltage relationship. ALS was here mimicked by a single point mutation in the superoxide dismutase 1 protein (SOD1), D90A, which had previously been identified in recessive, dominant and seemingly sporadic pedigrees. Cells carrying this point mutation displayed larger sodium currents, which eventually led to neurofilament aggregation, neurite degeneration and other phenotypes. We could confirm that the electrophysiological effect could be reversed by point mutation to D90D.

Our measurements validate the feasibility of measuring hiPSC ion channel currents using the APC platforms Qube and QPatch. Altogether, these results can facilitate evaluating the use of hiPSC for early drug development and in extension personal medicine.

Tuesday, 5th March

Sophion Seminar

9:30-11:00 AM – Sophion will be hosting a mini ion channel symposium in Room A at Baltimore conference center titled:

Electrophysiological characterization using automated patch clamp (QPatch and Qube) of hiPSC-derived neurological disease models, new automated patch clamp ion channel assays for CiPA cardiac safety testing (dynamic hERG and LQT3 late Na_V1.5) and Na_V1.7 drug discovery.

• Marc Rogers (Metrion Bioscience): Milnes and late Na_v1.5 for cardiac safety,
• Bryan Moyer (Amgen): HTS drug discovery,
• Kadla Rosholm (Sophion): hIPS neuronal disease models
• Sarah Williams (Charles River): Adaptive online V½ estimation.

Poster presentation

01:45 PM – Poster presentation:

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

Poster presenter: Application scientist Daniel Sauter

Location: Exhibit Hall A-E – Poster board No.: B285

Abstract:

Voltage-gated sodium channels (VGSC) are responsible for the initiation and propagation of action potentials in excitable cells. VGSC have been identified as excellent drug targets for treatment of pain, epilepsy and to other neurological disorders. Early compounds, however, were developed using empirical approaches. The identification of the molecular identity of VGSC in combination with technological advances, such as the automated patch clamp technique, provide the basis for a rational design of subtype-selective compounds.

To date, 9 functional mammalian isoforms (Na_V1.1–1.9) have been described in the literature. The various subtypes differ in their expression pattern and exhibit distinct biophysical and pharmacological profiles. All have in common that they produce a transient inward current in response to membrane depolarization. During this process, the VGSC transitions from a closed to an open into an inactivated state. Interestingly, inhibitor compounds often exhibit different pharmacological profiles dependent upon the ion channel conformational state.

In the present study, the second generation QPatch (QPatch II; Sophion Bioscience) was used in combination with adaptive voltage protocols to investigate state-dependent inhibition of tetrodotoxin (TTX) and tetracaine on 8 different VGSC subtypes (Na_V1.1-8). A first step was to determine the half-inactivation potential V_½(inactivation) for each individual cell. This value was then used during the next steps as 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. Both IC₅₀ values and biophysical parameters of the different subtypes align well with literature values.

SLAS2019

Make sure to come and see us at booth #1703 at SLAS2019 in Washington DC. The conference will take place at the Walter E. Washington Convention Center.

Read more about SLAS2019 here.

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 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.

Sophion User Meeting 2018 – Europe

Join us for a couple of days of great QPatch and Qube talks and good company

We are happy to invite you to our European Sophion User Meeting on 5th and 6th September 2018 and we are very pleased to announce that GSK in Stevenage kindly has offered to host the meeting this year.

We are preparing an interesting programme starting at noon on 5th September giving everyone a chance to travel to Stevenage in the morning. Wrap-up on 6th September just around lunchtime.

More information about the meeting will follow shortly.

Make sure to register for the meeting now as there are a limited number of seats.

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.

hCav1.2 recordings using QPatch

The development of screening assays for the Ca_V1.2 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 Ca_V1.2 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.

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 I_Na, I_Ca and I_Kr
• Paced and spontaneous action potentials
• We also show that the use of fluoride in the internal solution resulted in lower I_Ca 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

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.

Safety Pharmacology Society Annual Meeting 2018

We look forward to seeing you in Washington D.C. for the annual SPS meeting.

Venue:

Marriott Wardman Park
2660 Woodley Rd NW,
Washington, DC 20008

Come and see us for an ion channel talk at booth #113. Read more about the event here.

Channelopathy 2018

Join us and 180 peers in this international conference on ion channel diseases with emphasis on sharing the latest discoveries and technologies.

Venue: Feinberg School of Medicine in Chicago

Read more about the event here.

Neuroscience 2018

Hope to see you in San Diego in November for the annual SfN meeting. You can find us at booth #1933. Want to know more about Neuroscience click here.

You will get a chance to see our latest product – the QPatch II. Please visit our booth and ask for a demo.

Mads P G Korsgaard, global product manager, Sophion Bioscience A/S will be giving a presentation:

Title: Cutting-edge screening for ion channels: Na_V1.1 Case Study

Presentation time: Sunday November 4, 2018

2:00 PM at the Charles River booth #2519

Poster sessions:

Ligand-activation of GABA_A receptors on the automated patch clamp platforms QPatch and Qube 384 using conventional electrophysiology and optopharmacology

Application scientist, Melanie Schupp

Presentation time: Sunday, November 4, 2018, 2:00 PM – 3 PM, Poster board: D40

High-throughput screening of induced pluripotent stem cell-derived motor neurons on Qube and QPatch

Application scientist, Daniel Sauter

Presentation time: Monday, November 5, 2018, 8:00 AM –  9:00 AM, Poster board: B27

High throughput screening on Nav1.1 using Qube

The voltage-gated sodium channel Na_V1.1 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 Na_V1.1 have been shown to minimize cognitive dysfunction in transgenic mice with decreased levels of Na_V1.1 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 Na_V1.1 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.

Japanese Safety Pharmacology Society 9th Annual Meeting

We look forward to JSPS 9^th annual meeting at The University of Tokyo, Yayoi Auditorium. You can find the entire program here.

You can meet with our ion channel experts at our booth #I at the Yayoi Auditorium. We are participating in the stamp rally.

Poster Presentation

On Saturday, 10th February between 11.30 AM and 12.30 PM, Dr. Kazuya Tsurudome will present a poster titled:

Voltage and current clamp recordings from human iPS cell-derived cardiomyocytes on 384-channel automated patch-clamp system

Poster board no. 16

A list of all poster presented at JSPS can be found here.

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.

SLAS2018

This year you can meet the following Sophion people:

• Richard Kondo, sales manager, North America
• Weifeng Yu, director of customer support, North America
• Daniel Sauter, applications scientist, North America
• Thomas Binzer, vice president – R&d & Marketing

On Wednesday, February 7, 2018, 11:30 AM – 12:30 PM Daniel Sauter will be presenting a poster titled (Poster Number 1319-E-):

HT Automation for patch clamp based primary screen for Na_V1.1 using Qube384

Read more about SLAS2018 here.

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 Ca_V1.2 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 Ca_V1.2 modulation. Qube 384 provides a stable assay with the Ca_V1.2 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.

Happy New Year

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

Sophion User Meeting, Boston – Save the date!

We are still working with the agenda but can, at this point, reveal that we have the pleasure of having Julie Klint, Lundbeck as one of several speakers. Julie will give a talk titled: Finding Na_V1.1 activators – development and validation of a HTS suitable assay on the Qube. Also Noah Shuart from Xenon will be giving a talk.

Venue:

Hilton Boston/Woburn, 2 Forbes Rd. Woburn, MA 01801

Agenda:

April 10th

11.30 AM        Registration and lunch buffet

01.00 PM        Dr Kelly Gatfield, GSK: Tools for drug discovery: Early safety profiling and electrophysiology platforms for reducing attrition

01.30 PM        Dr Julie Klint, Lundbeck: Finding Na_V1.1 activators – development and validation of a HTS suitable assay for the Qube 384

02.00 PM        Dr Noah Shuart, Xenon: Using Qube to assess IPSC neuronal sodium currents and studying mechanism of VSD4 binding ligands in heterologous expression systems

02.30 PM        Coffee break

03.00 PM        Bryan Koci, Eurofins: Optimization of cardiac safety pharmacology assay on the QPatch HT

03.30 PM        Dr Kris Kahlig, Praxis Precision Medicines: Benchmarking Eleclazine: Biophysical characterization of a cardiac late I_Na inhibitor

04.00 PM        Dr Mads P G Korsgaard, Sophion Bioscience A/S: Update on Qube 384

04.30 PM        Dr Daniel Sauter, Sophion Bioscience, Inc.: Light stimulated electrophysiology on Qube: applications for ligand-gated ion channels

05.30 PM        Wine tasting and tapas

April 11th

08.30 AM        Registration and coffee

09.00 AM        Dr Kathryn Henckels, Amgen: Development of a TMEM16A QPatch assay for assessing small molecule antagonists

09.30 AM        Dr Robert Petroski, Dart: Using the QPatch HTX for lead optimization of ligand-gated ion channels

10.00 AM        Coffee break

10.30 AM        Dr Haoyu Zeng, Merck: Systematic Performance Comparison between QPatch and PatchXpress for Cardiac Ion Channel Assays, and GLP-readiness Evaluation of QPatch for the CiPA Paradigm

11.00 AM        Dr Rasmus B Jacobsen, Sophion Bioscience A/S: QPatch, Past, Present and Future

11.30 AM        Lunch at hotel

01.00 PM        Open house at our new premises

05.00 PM        Wrap-up

Sponsor:

Use this link for room booking at Hilton, Woburn.

Local hotels:

Hilton Boston/Woburn
2 Forbes Road, Woburn, MA
Phone: +1 781-932-0999

Crowne Plaza Boston/Woburn
15 Middlesex Canal Park Drive, Woburn, MA
Phone: +1 781-935-8760

Comfort Inn Boston/Woburn
14 Hill St, Woburn, MA 01801
Phone: +1 781-933-5363

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.

Biophysical Society 62nd Annual Meeting

We look forward to Biophysics 2018 where we will be doing a lot of activities:

First of all you can meet with our ion channel experts at our booth #518 at the Moscone Center.

Satellite Meeting

Friday, 16th February Sophion will be hosting the annually recurring satellite meeting, Drug Discovery for Ion Channels. 

See the agenda for the meeting here and make sure to sign up as the spaces are limited. 

Beer Tasting & Dinner

Saturday, 17th February we have the pleasure of inviting you to an informal evening of beer tasting, good food and great networking at the Bartlett Hall in San Francisco.

Make sure to sign up for this event here. Limited number of seats so be quick.

Ion Channel Mini Symposium

Tuesday, 20th February we will be having a short meeting at the conference center with the presentation title: Drug discovery and electrophysiological characterization using automated patch clamp (QPatch).

Venue: Room 6, Moscone Center, San Francisco – sign up here for the meeting:

10:30 – 11:00
Dr Damian Bell, Iontas Ltd.
Efficient ion channel cell line generation using MaxCyte electroporation and QPatch validation

11:00 – 11:30
Dr Daniel Sauter, Application Scientist, Sophion Bioscience A/S
Induced pluripotent stem cell-derived cardiomyocytes (Cor.4U) characterized on an automated planar patch clamp set up (QPatch HT)

11:30 – 12:00
Dr Alan Wickenden, Scientific Director & Fellow, Molecular & Cellular Pharmacology, Janssen R&D, L.L.C
NaViGATING the long and winding road to new analgesics: Discovery of potent, selective, closed-state peptide Nav1.7 blockers

Refreshments will be served.

Poster Presentation

Wednesday, 21st February between 10.30 AM and 11.30 AM, Dr Daniel Sauter will present a poster titled:

Induced pluripotent stem cell-derived cardiomyocytes (Cor.4U) characterized on an automated planar patch clamp setup (QPatch HT)

Poster board no. B301

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.

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.

Sophion Seminar & Workshop – Japan

You are invited to the Sophion Seminar & Workshop in Japan at Sophion Bioscience K.K.’s premises:

Venue

Waseda Research Park
1011 Nishitomida, Honjo, Saitama 367-0035, Japan

Programme

10:00          Registration

10:30          Welcome remarks and safety briefing
Dr. Yuji Tsurubuchi, Country Manager, Sophion Bioscience K.K., Japan

10:40          New ownership and future strategy at Sophion (tentative)
Mr. Thais Johansen, CEO, Sophion Bioscience A/S, Denmark

11:00          Educational lecture: Redox Physiology of TRP channels
Prof. Yasuo Mori, Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Japan

12:00          Lunch break and new Sophion K.K. lab tour
Each participant is assigned to either group A or B at the time of registration. The tour starts at 12:00 and 12:45 for group A and B, respectively. Lunch is served for group A after the tour.

13:30          Potency of ReproNeuro “Human iPS derived neurons” in the drug discovery support
Dr. Makoto Honda, ReproCELL, Inc., Japan

13:50          iPS derived human cells; iCel®, MyCell® DDP/ “disease in a dish” and ideas of application for drug discovery
Dr. Ko Zushida, Cellular Dynamics International Japan Co., Ltd.

14:20          Using the QPatch HTX to drive drug discovery: ligand-gated ion channels
Dr. Robert E. Petroski, Scientist IV/Manager Neurophysiology, Dart Neuroscience LLC, USA

15:00          Coffee break

15:30          Targeting T-type calcium channel for anti-pain drug discovery
Dr. Norio Hashimoto, Nissan Chemical Industries, Ltd., Japan

16:10          Exemplar of optical recording from neural and cardiac activities
Mr. Kenji Tsubokura, Brain Vision Co., Ltd., Japan

16:30          CiPA – novel drug safety assessment
Ms. Melanie Schupp, Application Scientist, Sophion Bioscience A/S, Denmark

16:50          Closing remarks
Mr. Naoto Ueda, President & CEO, Physio-Tech Co., Ltd., Japan

16.55          Bus transportation to the venue of reception

17:30          Reception (food and beverages are served)
Saitama Grand Hotel Honjo

19:30          Bus transportation to Honjo Waseda Station

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.

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.

Neuroscience

See you at Neuroscience 2017, the world’s largest neuroscience conference for scientists and physicians devoted to understanding the brain and nervous system. You can find us at booth #823 where we look forward to meet you for an ion channel talk.

Venue:  Walter E. Washington Convention Center, Washington, DC