患者由来および正常hIPS運動ニューロンにおけるQubeおよびQPatchによる評価

運動ニューロンは発声、歩行、呼吸および嚥下など、基幹的な随意筋活動を制御しています。 運動ニューロン疾患（MND）は、運動ニューロンを破壊する進行性神経障害の疾患群です。一部のMNDは遺伝性ですが、ほとんどのMNDの原因は解明されていません。

患者由来と野生型のhIPS運動ニューロンを用いた評価によりスクリーニングできることが、長い間多くのユーザーから望まれていました。

新たにSfN 2018で発表するポスターでは、QubeとQPatchのいずれでも良好な成功率にて、正常および患者由来の運動ニューロンでの評価が可能であることを示しています。

• 脊髄性筋萎縮症（SMA）または筋萎縮性側索硬化症（ALS）患者由来のヒトiPS細胞を用いて電気生理学的特性を評価し、それらの結果を対照の細胞株と比較した。
• ALS罹患細胞では、正常細胞と比較してナトリウム電流が有意に増加したが、単一の点突然変異の導入により回復することができた。

ポスターはこちらからご覧いただけます。

Come and see our brand new QPatch II

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

Read more about our activities at the conference here.

See you in San Diego in November.

31 new Publications and Reports from Q3

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

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

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

Peer reviewed publications

• Sokolov et Al 2018. Co-expression of β Subunits with the Voltage-Gated Sodium Channel NaV1.7: the Importance of Subunit Association and Phosphorylation and Their Effects on Channel Pharmacology and Biophysics. Journal of Molecular Neuroscience (LINK)
• Kanase et Al 2018. 4-Substituted carbamazepine derivatives: Conformational analysis and sodium channel-blocking properties. Bioorganic & Medicinal Chemistry, Volume 26, Issue 9 (LINK)
• Gonçalves et Al. 2018. Direct evidence for high affinity blockade of NaV1.6 channel subtype by huwentoxin-IV spider peptide, using multiscale functional approaches. Neuropharmacology, Volume 133, 404-414 (LINK)
• Zha et Al. 2018. Design, synthesis and biological evaluation of tetrahydronaphthyridine derivatives as bioavailable CDK4/6 inhibitors for cancer therapy. European Journal of Medicinal Chemistry, Volume 148, Pages 140-153 (LINK)
• Israel et Al. 2018. The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and Excitatory Activities on Human NaV1.6. J. Med. Chem., 2018, 61 (4), pp 1730–1736 (LINK)
• Loucif et Al. 2018. GI‐530159, a novel, selective, mechanosensitive two‐pore‐domain potassium (K2P) channel opener, reduces rat dorsal root ganglion neuron excitability. British Journal of Pharmacology (LINK)
• Xu et Al. 2018. Synthesis and biological evaluation of a series of multi-target N-substituted cyclic imide derivatives with potential antipsychotic effect. European Journal of Medicinal Chemistry, Volume 145, Pages 74-85 (LINK)
• Agwa et Al 2018. Efficient Enzymatic Ligation of Inhibitor Cystine Knot Spider Venom Peptides: Using Sortase A To Form Double-Knottins That Probe Voltage-Gated Sodium Channel Na_V7. Bioconjug Chem. 2018 Sep 12. (LINK)
• Colley et Al 2018. Screening strategies for the discovery of ion channel monoclonal antibodies. Current Protocols in Pharmacology, 82, e44. (LINK)
• Robinson et Al 2018. A comprehensive portrait of the venom of the giant red bull ant, Myrmecia gulosa, reveals a hyperdiverse hymenopteran toxin gene family. Science Advances 12 Sep 2018:Vol. 4, no. 9 (LINK)
• Procopiou et Al 2018. Discovery of (S)-3-(3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a Nonpeptidic αvβ6 Integrin Inhibitor for the Inhaled Treatment of Idiopathic Pulmonary Fibrosis. Med. Chem (LINK)
• Ghovanloo et Al 2018. Inhibitory effects of cannabidiol on voltage-dependent sodium currents. Journal of Biological Chemistry (LINK)
• Bankar et Al 2018. Selective Nav1.7 Antagonists with Long Residence Time Show Improved Efficacy against Inflammatory and Neuropathic Pain. (LINK)

Posters

• Bettini et Al 2018. NMDA Receptor Modulators in QPatch. Evotech Gmbh (LINK)
• Boddum et Al 2018. Optical modulation of ion channels. Sophion Bioscience. (LINK)
• Boddum et Al 2018. GABAA receptor pharmacology evaluted in overexpressing HEK cells and primary astrocytes on QPatch. Sophion Bioscience. (LINK)
• Standing et Al 2018. Development of high-throughput electrophysiological assay for the screening of hERG ion channel modulators using Sophion Qube 384. GlaxoSmithKline (LINK)
• Klint et Al 2018. HT Automation for patch clamp based primary screen for Nav1.1 using Qube 384. Lundbeck A/S (LINK).
• Bouyer and Hebeisen 2018. Na_V5 big late : An inactivation deficient mutant of Na_V1.5 as screening tool for late sodium currents of the cardiac action potential. B’SYS (LINK)
• Douglin Guo et Al. 2018 Simultaneous measurement of cardiac Na_v5 peak and late current in an automated QPatch platform. Pfizer. SPS 2018
• Koci et Al 2018. Optimization of Cardiac CiPA targets (Ca_v2 and KCNQ1/MinK) on the QPatch HT automated system. Eurofins. SPS 2018
• Huphries et Al 2018. New CiPA ion channel cell lines and assays for in vitro proarythmia risk assessment. Metrion Biosciences. SPS 2018. (Will be uploaded soon)
• Donglin Guo et Al 2018. Simultaneous measurement of cardiac hERG and Na_v5 currents using an automated Qube patch clamp platform. Pfizer. SPS 2018. (Will be uploaded soon)
• Renganathan et Al 2018. Automated High Throughput Na+ Late current Assay on QPatch HT platform for CiPA28. Eurofins. SPS 2018 (Will be uploaded soon)
• Lindqvist and Christensen 2018. Estimating hERGdrug binding using temperature-controlled high throughput automated patch clamp. Sophion Bioscience. SPS 2018 (Will be uploaded soon)

Application Reports

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

New papers, posters and reports (Q3 2018)

Papers:

• Sokolov et Al 2018. Co-expression of β Subunits with the Voltage-Gated Sodium Channel NaV1.7: the Importance of Subunit Association and Phosphorylation and Their Effects on Channel Pharmacology and Biophysics. Journal of Molecular Neuroscience (LINK)
• Kanase et Al 2018. 4-Substituted carbamazepine derivatives: Conformational analysis and sodium channel-blocking properties. Bioorganic & Medicinal Chemistry, Volume 26, Issue 9 (LINK)
• Gonçalves et Al. 2018. Direct evidence for high affinity blockade of NaV1.6 channel subtype by huwentoxin-IV spider peptide, using multiscale functional approaches. Neuropharmacology, Volume 133, 404-414 (LINK)
• Zha et Al. 2018. Design, synthesis and biological evaluation of tetrahydronaphthyridine derivatives as bioavailable CDK4/6 inhibitors for cancer therapy. European Journal of Medicinal Chemistry, Volume 148, Pages 140-153 (LINK)
• Israel et Al. 2018. The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and Excitatory Activities on Human NaV1.6. J. Med. Chem., 2018, 61 (4), pp 1730–1736 (LINK)
• Loucif et Al. 2018. GI‐530159, a novel, selective, mechanosensitive two‐pore‐domain potassium (K2P) channel opener, reduces rat dorsal root ganglion neuron excitability. British Journal of Pharmacology (LINK)
• Xu et Al. 2018. Synthesis and biological evaluation of a series of multi-target N-substituted cyclic imide derivatives with potential antipsychotic effect. European Journal of Medicinal Chemistry, Volume 145, Pages 74-85 (LINK)
• Agwa et Al 2018. Efficient Enzymatic Ligation of Inhibitor Cystine Knot Spider Venom Peptides: Using Sortase A To Form Double-Knottins That Probe Voltage-Gated Sodium Channel Na_V7. Bioconjug Chem. 2018 Sep 12. (LINK)
• Colley et Al 2018. Screening strategies for the discovery of ion channel monoclonal antibodies. Current Protocols in Pharmacology, 82, e44. (LINK)
• Robinson et Al 2018. A comprehensive portrait of the venom of the giant red bull ant, Myrmecia gulosa, reveals a hyperdiverse hymenopteran toxin gene family. Science Advances 12 Sep 2018:Vol. 4, no. 9 (LINK)
• Procopiou et Al 2018. Discovery of (S)-3-(3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a Nonpeptidic αvβ6 Integrin Inhibitor for the Inhaled Treatment of Idiopathic Pulmonary Fibrosis. Med. Chem (LINK)

Posters:

• Bettini et Al 2018. NMDA Receptor Modulators in QPatch (LINK)
• Boddum et Al 2018. Optical modulation of ion channels (LINK)
• Boddum et Al 2018. GABAA receptor pharmacology evaluted in overexpressing HEK cells and primary astrocytes on QPatch (LINK)
• McCoull et Al 2018. Development of a novel screening system to identify activators of Two-pore domain potassium channels (K2Ps)(LINK)
• Standing et Al 2018. Development of high-throughput electrophysiological assay for the screening of hERG ion channel modulators using Sophion Qube 384 (LINK)
• Klint et Al 2018. HT Automation for patch clamp based primary screen for Nav1.1 using Qube 384. (LINK)
• Bouyer and Hebeisen 2018. Na_V5 big late : An inactivation deficient mutant of Na_V1.5 as screening tool for late sodium currents of the cardiac action potential (LINK)

Application reports:

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

新機種QPatch IIの発表について

QPatchは2000年代の初めより、安全性薬理および創薬スクリーニングの研究フィールドにおいて、イオンチャネル評価系のベンチマーク的なオートパッチクランプシステムして、日本国内でも多くユーザー様にご愛用頂いて参りました。

今回発表いたしますQPatch IIでは、QPatchで高く評価されてきたデータの品質を維持しつつ、実際の運用における作業効率と使い勝手の良さが著しく向上しております。

9月30日（日）より米国ワシントンDCにて開催されるSPS（安全性薬理学会）では、Sophionのブース（113番）にてQPatch IIの実機の展示を行い、日本からのご参加の皆さまには日本語でこの新機種の発表会を行います。SPSへご参加なさる方は、是非Sophionのブースにお越し頂くとともに、発表会へもご参加下さい。なお、発表会の日程と会場はブースにてお知らせいたします。

また10月19日（金）には、東京にてSophionセミナーが開催され、そちらの会場でもQPatch IIの実機展示を行います。本セミナーでも新機種の機能とバリデーションデータ等を紹介いたしますので、皆さまのお越しをお待ち申し上げております。お申し込みはこちらからお手続きをください。セミナーの概要はこちらになります。

なお、年内には当社の国内ラボにもQPatch IIが設置される予定でございます。新機種のデモをご希望のお客様は、info@sophion.co.jpまでメールにてご予約のリクエストをお送りください。後ほど担当者よりご連絡差し上げます。

Sophion co-organized channelopathy symposium in China

ソフィオン・バイオサイエンスは、7月中旬に北京大学で

「チャネル病と創薬に関する国際シンポジウム – 薬物標的としてのイオンチャンネル」

というタイトルでチャネロパチーミーティングを共催しました．

この会議は，北京大学健康科学センターの天然およびバイオミメティック薬国家重点研究室によって主催されました．

中国の基礎研究者，医師，および製薬企業のためのチャネロパシー領域におけるコミュニケーションと知識交換のためのプラットフォームを提供するという目的で開催されました．中国と海外の講演者が招かれ，イオンチャンネルならびに関連疾患に関する最新の科学的アイデア，最先端技術および最新の研究成果の発表が行われました．弊社のアプリケーションサイエンティストのMelanie Schuppが「Nav1.1のハイスループットスクリーニング」について講演しました．

ソフィオンではこのイベントを中国で共催し，多くの研究者の交流に寄与することができたことを大変うれしく思っています．

プログラムと講演者の経歴についてはこちらをご覧ください．（読み込みには時間がかかる場合がございます）

Super-short ligand exposure time on Qube Opto 384

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

RuBi-GABA activation followed by wash-out

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

RuBi-GABA activation during perfusion

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

Updated privacy policy

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

In short:

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

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

You can read the full privacy policy here

Light activated rubi-GABA on Qube Opto 384

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

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

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

Concentration-response relationship

• HEK 293 / GABA_A (α₅β₃γ₂)
• Caged GABA (Rubi-GABA – Tocris)
• Light: 475 nm for 200 ms @ 100% light output intensity
• Rubi-GABA: 3-fold dilution series
• EC50: 10,6 uM +/- 0,5 uM

Optical dose-response relationship

• HEK 293 / GABA_A (α₅β₃γ₂)
• Caged GABA (Rubi-GABA – Tocris)
• Light: 475 nm for 200 ms @ 10-100% light output intensities

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