APC & ACADEMIA

包括的自動パッチクランプ

QPatch II – 生理学ソリューションでギガオームシールを取得できる業界唯一のプラットフォームです。個別の圧力パルス制御、適応電圧プロトコル、ガラスコーティングされた液体チャネル、自動Rs補正などと組み合わされます。QPatchⅡは、手動型パッチクランプに最も近い自動パッチクランプです。

自動パッチクランプをツールパックとして所有する研究所が増えています。研究成果と早いフィードバックに注目が集まる中、従来の手動型パッチクランプに加え、自動パッチクランプの価値が高まっています。

 

 数百〜数千倍のデータスループット

 ユーザースキルに依存しない簡単操作

 学術研究機関を上回るテクニカルナレッジ

 細胞株、幹細胞、プライマリ細胞に適用可能

 

「電気生理学者の間では、いまだにベンチマークとしてMPCが行われていますが、多数のトレーニングと技術的な経験を必要とすることがデメリットです。これは、成果と研究プログラムの蓋然性が注目されている学術研究機関で、ますます問題になっています。」

(Bell and Dallas 2018)

 

あなたの研究室に未来を

 

私たちは、研究者が機器の操作に時間を費やすのではなく、優れた研究の実現に時間を費やしてほしいと考えています。
そのためには、最先端の測定ソリューションでも使いやすく、多くのユーザー用に設計された高い耐久性を備えている機器が必要です。Sophionのシステムがリリースされ、10年~15年経ちますが問題なく機能しています。システムの操作も10分ほどで簡単に習得できるため、結果の分析や次の新たな研究に時間を費やすことができます。

しかし予算の心配もありますよね?このシステムは10人~15人の熟練した電気生理学者に匹敵する仕事を簡単にこなしますが、価格はその人件費には及びません。ぜひお問い合わせください。驚くことでしょう。

 

 装置や機器の操作ではなく研究に時間を費やす

 より多くのデータポイントと反復で研究スピードを上げる

 製薬業界の将来の可能性を博士や研究員に提供する

 耐久性のある研究環境を確立する

 

中核研究室 – 共有は思いやり

Qube 384 – 384個の個別アンプ、スタッカー、Rs補正、適応電圧プロトコル、温度制御などを備えたQube384は、大規模なライブラリのスクリーニング用に設計されていますが、多くのクローンがある場合、細胞間の変動が大きい場合、テストのための多くの複製が必要な場合などにも便利です。

過去のAPC機器への投資は、製薬会社と少数のアカデミックグループにのみ限られていましたが、中核研究施設で機器を共有することが徐々に主流となっています。

 

 部門間で技術の共有

 部門間で知識の共有

 部門間でコストの分割

 

「学界で採用されているモデルの1つは、複数の研究グループで資金を提供し、必要な実験を生む中核施設です。」

(Bell and Dallas 2018)

 

科学的価値 – それは間違いない

「一枚の絵は千以上のことを語る」論文全般にも同じことが言えます。
QPatchやQube384を使用している学術機関発行の出版物リストは、
以下を参照してください。

 

APCソリューションについては、こちらをクリ
ックしてください – QPatch IIQube 384

 

出版物リスト(学術機関より)

– 包括リストについては 公表文献など を参照

 

Agwa, Akello J 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(V)1.7.” Bioconjugate Chemistry 29(10): 3309–19.

Agwa, Akello J. et al. 2020. “Manipulation of a Spider Peptide Toxin Alters Its Affinity for Lipid Bilayers and Potency and Selectivity for Voltage-Gated Sodium Channel Subtype 1.7.” Journal of Biological Chemistry 295(15): 5067–80. https://www.jbc.org/content/early/2020/03/05/jbc.RA119.012281.full.pdf.

Ai, Yong et al. 2015. “Synthesis and Biological Evaluation of Novel Olean-28,13β-Lactams as Potential Antiprostate Cancer Agents.” Journal of Medicinal Chemistry 58(11): 4506–20. https://doi.org/10.1021/jm5020023.

Al-Sabi, Ahmed et al. 2010. “Arrangement of Kv1 α Subunits Dictates Sensitivity to Tetraethylammonium.” Journal of General Physiology 136(3): 273–82.

Al-Sabi, Ahmed et al. 2017. “A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves That Improves Their Impaired Axonal Conduction.” Journal of Medicinal Chemistry 60(6): 2245–56. https://doi.org/10.1021/acs.jmedchem.6b01262.

Arias, Hugo R et al. 2016. “Positive Allosteric Modulators of Α7 Nicotinic Acetylcholine Receptors Affect Neither the Function of Other Ligand- and Voltage-Gated Ion Channels and Acetylcholinesterase, nor β-Amyloid Content.” The International Journal of Biochemistry & Cell Biology 76: 19–30. http://www.sciencedirect.com/science/article/pii/S1357272516300930.

Bagchi, Bandita et al. 2014. “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.” PLoS ONE 9(2).

Bell, Damian C., and Mark L. Dallas. 2018. “Using Automated Patch Clamp Electrophysiology Platforms in Pain-Related Ion Channel Research: Insights from Industry and Academia.” British Journal of Pharmacology 175(12): 2312–21.

Billakota, Santoshi et al. 2019. “Personalized Medicine: Vinpocetine to Reverse Effects of GABRB3 Mutation.” Epilepsia 60(12): 2459–65.

Billet, Arnaud, Lionel Froux, John W. Hanrahan, and Frederic Becq. 2017. “Development of Automated Patch Clamp Technique to Investigate CFTR Chloride Channel Function.” Frontiers in Pharmacology 8(APR): 1–10.

Brown, Maile R. et al. 2016. “Physiological Modulators of Kv3.1 Channels Adjust Firing Patterns of Auditory Brain Stem Neurons.” Journal of Neurophysiology 116(1): 106–21.

Cardoso, Fernanda C. et al. 2015. “Identification and Characterization of ProTx-III [μ-TRTX-Tp1a], a New Voltage-Gated Sodium Channel Inhibitor from Venom of the Tarantula Thrixopelma Pruriens.” Molecular Pharmacology 88(2): 291–303.

Choi, Ryan et al. 2020. “Bumped Kinase Inhibitors as Therapy for Apicomplexan Parasitic Diseases: Lessons Learned.” International Journal for Parasitology. http://www.sciencedirect.com/science/article/pii/S0020751920300564.

Chow, Chun Yuen et al. 2020. “A Selective NaV1.1 Activator with Potential for Treatment of Dravet Syndrome Epilepsy.” Biochemical Pharmacology (February): 113991. https://doi.org/10.1016/j.bcp.2020.113991.

Chow, Chun Yuen et al. 2020. “Venom Peptides with Dual Modulatory Activity on the Voltage-Gated Sodium Channel NaV1.1 Provide Novel Leads for Development of Antiepileptic Drugs.” ACS Pharmacology & Translational Science 3(1): 119–34. https://doi.org/10.1021/acsptsci.9b00079.

Coleman, Nichole et al. 2014. “New Positive Ca2+-Activated K+ Channel Gating Modulators with Selectivity for KCa3.1.” Molecular Pharmacology 86(3): 342–57.

Daly, D et al. 2015. “Porphyrin Derivatives as Potent and Selective Blockers of Neuronal Kv1 Channels.” Chem. Commun. 51(6): 1066–69. http://dx.doi.org/10.1039/C4CC05639F.

Damann, Nils et al. 2020. “In Vitro Characterization of the Thermoneutral Transient Receptor Potential Vanilloid-1 (TRPV1) Inhibitor GRTE16523.” European Journal of Pharmacology 871: 172934. http://www.sciencedirect.com/science/article/pii/S0014299920300261.

Danahay, Henry L. et al. 2020. “TMEM16A Potentiation: A Novel Therapeutic Approach for the Treatment of Cystic Fibrosis.” American journal of respiratory and critical care medicine 201(8): 946–54. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159426/.

Das, Pragnya et al. 2019. “Novel Chitohexaose Analog Protects Young and Aged Mice from CLP Induced Polymicrobial Sepsis.” Nature Scientific Reports 9(1): 1–12.

del Álamo, Juan C. et al. 2016. “High Throughput Physiological Screening of IPSC-Derived Cardiomyocytes for Drug Development.” Biochimica et Biophysica Acta – Molecular Cell Research 1863(7): 1717–27. http://dx.doi.org/10.1016/j.bbamcr.2016.03.003.

Deuis, Jennifer R. et al. 2016. “Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain.” Toxins 8(3): 1–19.

Deuis, Jennifer R. et al. 2017. “Pharmacological Characterisation of the Highly Na v 1.7 Selective Spider Venom Peptide Pn3a.” Nature Scientific Reports 7(January): 1–19.

Diness, Jonas Goldin et al. 2017. “Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca2+-Activated K+ Channels in Pigs.” Circulation: Arrhythmia and Electrophysiology 10(10): 1–13.

Flinspach, M. et al. 2017. “Insensitivity to Pain Induced by a Potent Selective Closed-State Nav1.7 Inhibitor.” Nature Scientific Reports 7(January): 1–16.

Franz, Denise, Hervør Lykke Olsen, Oliver Klink, and Jan Gimsa. 2017. “Automated and Manual Patch Clamp Data of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons.” Nature Scientific Data 4: 1–11.

Ghovanloo, Mohammad Reza et al. 2019. “Inhibitory Effects of Cannabidiol on Voltage-Dependent Sodium Currents.” Journal of Biological Chemistry 293(43): 16546–58.

Grillo, Alessandro et al. 2019. “Development of Novel Multipotent Compounds Modulating Endocannabinoid and Dopaminergic Systems.” European Journal of Medicinal Chemistry 183: 111674. https://doi.org/10.1016/j.ejmech.2019.111674.

Hammami, Sofia et al. 2009. “Cell Volume and Membrane Stretch Independently Control K+ Channel Activity.” Journal of Physiology 587(10): 2225–31.

Hao, Yuchen, Jingshu Tang, and KeWei Wang. 2015. “Development of Automated Patch Clamp Assay for Evaluation of Α7 Nicotinic Acetylcholine Receptor Agonists in Automated QPatch-16.” ASSAY and Drug Development Technologies 13(3): 174–84. https://doi.org/10.1089/adt.2014.622.

He, Linhong et al. 2018. “Design, Synthesis and Biological Evaluation of 7H-Pyrrolo[2,3-d]Pyrimidin-4-Amine Derivatives as Selective Btk Inhibitors with Improved Pharmacokinetic Properties for the Treatment of Rheumatoid Arthritis.” European Journal of Medicinal Chemistry 145: 96–112. http://www.sciencedirect.com/science/article/pii/S0223523417311108.

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): 1–20.

Inserra, Marco C. et al. 2017. “Multiple Sodium Channel Isoforms Mediate the Pathological Effects of Pacific Ciguatoxin-1.” Nature Scientific Reports 7(January): 1–19.

Israel, Mathilde R et al. 2018. “The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and Excitatory Activities on Human NaV1.6.” Journal of Medicinal Chemistry 61(4): 1730–36. https://doi.org/10.1021/acs.jmedchem.7b01609.

Jalily, Pouria H. et al. 2020. “Put a Cork in It: Plugging the M2 Viral Ion Channel to Sink Influenza.” Antiviral Research 178(February): 104780. https://www.sciencedirect.com/science/article/pii/S0166354219305820.

Jenkins, David Paul et al. 2013. “Development of a QPatch Automated Electrophysiology Assay for Identifying KCa3.1 Inhibitors and Activators.” Assay and Drug Development Technologies 11(9–10): 551–60.

Jin, Ai Hua et al. 2015. “δ-Conotoxin SuVIA Suggests an Evolutionary Link between Ancestral Predator Defence and the Origin of Fish-Hunting Behaviour in Carnivorous Cone Snails.” Proceedings of the Royal Society B: Biological Sciences 282(1811).

Kaproń, Barbara et al. 2019. “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 129: 42–57. http://www.sciencedirect.com/science/article/pii/S0928098718305530.

Klint, Julie K., Yanni K.Y. Chin, and Mehdi Mobli. 2015. “Rational Engineering Defines a Molecular Switch That Is Essential for Activity of Spider-Venom Peptides against the Analgesics Target NaV1.7.” Molecular Pharmacology 88(6): 1002–10.

Kramer, James et al. 2013. “MICE Models: Superior to the HERG Model in Predicting Torsade de Pointes.” Nature Scientific Reports 3: 1–7.

Kramer, James 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 10(1): 1–15. http://dx.doi.org/10.1038/s41598-020-62344-w.

Kristof, Arnold S. et al. 2017. “An Official American Thoracic Society Workshop Report: Translational Research in Rare Respiratory Diseases.” Annals of the American Thoracic Society 14(8): 1239–47.

Łażewska, Dorota et al. 2017. “Biphenyloxy-Alkyl-Piperidine and Azepane Derivatives as Histamine H3 Receptor Ligands.” Bioorganic & Medicinal Chemistry 25(20): 5341–54. http://www.sciencedirect.com/science/article/pii/S0968089617310696.

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. https://doi.org/10.1016/j.ejmech.2020.112309.

Loucif, Alexandre J.C. et al. 2018. “GI-530159, a Novel, Selective, Mechanosensitive Two-Pore-Domain Potassium (K 2P ) Channel Opener, Reduces Rat Dorsal Root Ganglion Neuron Excitability.” British Journal of Pharmacology 175(12): 2272–83.

Marcinkowska, Monika et al. 2016. “Design, Synthesis, and Biological Evaluation of Fluorinated Imidazo[1,2-a]Pyridine Derivatives with Potential Antipsychotic Activity.” European Journal of Medicinal Chemistry 124: 456–67. http://www.sciencedirect.com/science/article/pii/S0223523416307152.

Menegon, A. et al. 2017. “A New Electro-Optical Approach for Conductance Measurement: An Assay for the Study of Drugs Acting on Ligand-Gated Ion Channels.” Nature Scientific Reports 7(September 2016): 1–13.

Miner, Kent et al. 2019. “Drug Repurposing: The Anthelmintics Niclosamide and Nitazoxanide Are Potent TMEM16A Antagonists That Fully Bronchodilate Airways.” Frontiers in Pharmacology 10(FEB).

Mistry, Hitesh B., Mark R. Davies, and Giovanni Y. Di Veroli. 2015. “A New Classifier-Based Strategy for in-Silico Ion-Channel Cardiac Drug Safety Assessment.” Frontiers in Pharmacology 6(MAR): 1–6.

Mueller, Alexander et al. 2020. “Mapping the Molecular Surface of the Analgesic Na V 1.7-Selective Peptide Pn3a Reveals Residues Essential for Membrane and Channel Interactions.” ACS Pharmacology & Translational Science. https://pubs.acs.org/doi/abs/10.1021/acsptsci.0c00002.

Nausch, Bernhard et al. 2014. “NS19504: A Novel BK Channel Activator with Relaxing Effect on Bladder Smooth Muscle Spontaneous Phasic Contractions.” Journal of Pharmacology and Experimental Therapeutics 350(3): 520–30.

Okada, Jun Ichi et al. 2015. “Screening System for Drug-Induced Arrhythmogenic Risk Combining a Patch Clamp and Heart Simulator.” Science Advances 1(4): 1–8.

Okumu, Antony et al. 2020. “Novel Bacterial Topoisomerase Inhibitors Derived from Isomannide.” European Journal of Medicinal Chemistry 199: 112324. https://doi.org/10.1016/j.ejmech.2020.112324.

Ong, Seow Theng et al. 2019. “Extracellular K + Dampens T Cell Functions: Implications for Immune Suppression in the Tumor Microenvironment.” Bioelectricity 1(3): 169–79.

Petrou, Terry et al. 2017. “Intracellular Calcium Mobilization in Response to Ion Channel Regulators via a Calcium-Induced Calcium Release Mechanism.” Journal of Pharmacology and Experimental Therapeutics 360(2): 378–87.

Prashanth, Jutty Rajan, Nojod Hasaballah, and Irina Vetter. 2017. “Pharmacological Screening Technologies for Venom Peptide Discovery.” Neuropharmacology 127: 4–19. http://www.sciencedirect.com/science/article/pii/S0028390817301302.

Procopiou, Panayiotis A. et al. 2018. “Discovery of (S)-3-(3-(3,5-Dimethyl-1H-Pyrazole-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.” Journal of Medicinal Chemistry 61(18): 8417–43. https://doi.org/10.1021/acs.jmedchem.8b00959.

Rao, Vidhya R., Mathew Perez-Neut, Simon Kaja, and Saverio Gentile. 2015. “Voltage-Gated Ion Channels in Cancer Cell Proliferation.” Cancers 7(2): 849–75.

Reyes-Corral, Marta et al. 2019. “Differential Free Intracellular Calcium Release by Class II Antiarrhythmics in Cancer Cell Lines.” Journal of Pharmacology and Experimental Therapeutics 369(1): 152–62.

Robinson, Samuel D. 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 4(9): 1–13.

Shcherbatko, Anatoly et al. 2016. “Modulation of P2X3 and P2X2/3 Receptors by Monoclonal Antibodies.” Journal of Biological Chemistry 291(23): 12254–70.

Simó-Vicens, Rafel et al. 2017. “Effect of Antiarrhythmic Drugs on Small Conductance Calcium-Activated Potassium Channels.” European Journal of Pharmacology 803: 118–23. http://www.sciencedirect.com/science/article/pii/S0014299917302091.

Singh, Vinayak et al. 2017. “The Inosine Monophosphate Dehydrogenase, GuaB2, Is a Vulnerable New Bactericidal Drug Target for Tuberculosis.” ACS Infectious Diseases 3(1): 5–17.

Skarsfeldt, Mark A et al. 2016. “PH-Dependent Inhibition of K2P3.1 Prolongs Atrial Refractoriness in Whole Hearts.” Pflügers Archiv – European Journal of Physiology 468(4): 643–54. https://doi.org/10.1007/s00424-015-1779-0.

Solly, Kelli et al. 2015. “High-Throughput Screen of GluK1 Receptor Identifies Selective Inhibitors with a Variety of Kinetic Profiles Using Fluorescence and Electrophysiology Assays.” Journal of Biomolecular Screening 20(6): 708–19.

Sousa, Silmara R. et al. 2017. “Discovery and Mode of Action of a Novel Analgesic β-Toxin from the African Spider Ceratogyrus Darlingi.” PLoS ONE 12(9): 1–22.

Tay, Bryan et al. 2019. “Development of a High-Throughput Fluorescent No-Wash Sodium Influx Assay.” PLoS ONE 14(3): 1–14.

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. https://doi.org/10.1021/acs.bioconjchem.9b00744.

Wacker, Sören J. et al. 2012. “Identification of Selective Inhibitors of the Potassium Channel Kv1.1-1.2(3) by High-Throughput Virtual Screening and Automated Patch Clamp.” ChemMedChem 7(10): 1775–83.

Walsh, Kenneth B. 2020. “Screening Technologies for Inward Rectifier Potassium Channels: Discovery of New Blockers and Activators.” SLAS Discovery.

Wang, Dan et al. 2018. “Synthesis of Pseudellone Analogs and Characterization as Novel T-Type Calcium Channel Blockers.” Marine Drugs 16(12): 1–12.

Wu, Chunhui et al. 2019. “Synthesis and Biological Evaluation of Five-Atom-Linker-Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile.” ChemMedChem 14(24): 2042–51. https://doi.org/10.1002/cmdc.201900439.

Xu, Mingshuo 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 145: 74–85. https://doi.org/10.1016/j.ejmech.2017.12.099.

Yadav, Saurabh, Vishnu Kumar Dwivedi, Sarika Gupta, and Avadhesha Surolia. 2018. “Benzothiophenes as Potent Analgesics against Neuropathic Pain.” Advances in Experimental Medicine and Biology 1112: 245–54.

Yang, Daryl C. et al. 2016. “The Snake with the Scorpion’s Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake (Calliophis Bivirgatus).” Toxins 8(10): 1–21.

Yang, Yang et al. 2016. “Scaffold Hopping toward Agomelatine: Novel 3, 4-Dihydroisoquinoline Compounds as Potential Antidepressant Agents.” Nature Scientific Reports 6(September): 1–20.

Zha, Chuantao et al. 2018. “Design, Synthesis and Biological Evaluation of Tetrahydronaphthyridine Derivatives as Bioavailable CDK4/6 Inhibitors for Cancer Therapy.” European Journal of Medicinal Chemistry 148: 140–53. http://www.sciencedirect.com/science/article/pii/S0223523418301442.

Zhang, Zhengping et al. 2016. “A Novel Acetylcholinesterase Inhibitor and Calcium Channel Blocker SCR-1693 Improve Aβ25–35-Impaired Mouse Cognitive Function.” Psychopharmacology 233(4): 599–613. https://doi.org/10.1007/s00213-015-4133-5.

Zhu, Fang et al. 2020. “Structural Optimization of Aminopyrimidine-Based CXCR4 Antagonists.” European Journal of Medicinal Chemistry 187: 111914. http://www.sciencedirect.com/science/article/pii/S0223523419310669.