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The Nav1.5 late current in WT and Nav1.5 ΔKPQ mutant channels: An automated patch-clamp LQT3 electrophysiological assay

The cardiac late Na+ current (late INa) generates persistent inward currents throughout the plateau phase of the ventricular action potential and is an important determinant of repolarisation rate, EADs and arrythmia risk. As inhibition of late INa can offset drug effects on hERG and other repolarising K+ conductances it is one of the key cardiac channels in the Comprehensive in vitro Proarrythmia Assay CiPA panel being developed by the FDA to improve human clinical arrythmia risk assessment.

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Designing multiple assay protocols for ligand-gated ion channels using the stacked-tip feature on the Patchliner and SP384i platforms

Marc Rogers (Metrion CSO) presents a talk at the Nanion Virtual User Meeting 2020 entitled “Designing multiple assay protocols for ligand-gated ion channels using the stacked-tip feature on the Patchliner and SP384i platforms”. 14th October 2020.

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Ion Channel Discovery – Partnering to Access Specialized Expertise

Stevens, E. B and Wright, P. D Future Drug Discovery, 2020.

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Using new in vitro cardiac ion channel assays and in silico models to predict proarrhythmia risk with automated patch-clamp

The FDA’s Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is designed to remove the over-reliance on hERG data to predict human clinical cardiac risk, with recent results suggesting that inclusion of additional cardiac ion channels and assays (e.g. peak and late Nav1.5, Cav1.2, dynamic hERG) improve risk predictions of in silico action potential models.

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Validation and optimization of automated patch-clamp voltage-gated Ca2+ channel assays

Marc Rogers (Metrion CSO) takes part in a collaborative webinar with Nanion Technologies entitled “Validation and optimization of automated patch-clamp voltage-gated Ca2+ channel assays”.

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Cross-site and cross-platform variability of automated patch clamp assessments of drug effects on human cardiac currents in recombinant cells

Kramer, J.; Himmel, H. M.; Lindqvist, A.; Stoelzle-Feix, S.; Chaudhary, K. W.; Li, D.; Bohme, G. A.; Bridgland-Taylor, M.; Hebeisen, S.; Fan, J.; Renganathan, M.; Imredy, J.; Humphries, E. S. A.; Brinkwirth, N.; Strassmaier, T.; Ohtsuki, A.; Danker, T.; Vanoye, C.; Polonchuk, L.; Fermini, B.; Beck Pierson, J.; Gintant, G. Scientific Reports, 2020, 10; 5627

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A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm

Bradley J. Ridder, Derek J. Leishman, Matthew Bridgland-Taylor, Mohammadreza Samieegohar, Xiaomei Han, Wendy W. Wu, Aaron Randolph, Phu Tran, Jiansong Sheng, Timm Danker, Anders Lindqvist, Daniel Konrad, Simon Hebeisen, Liudmila Polonchuk, Evgenia Gissinger, Muthukrishnan Renganathan, Bryan Koci, Haiyang Wei, Jingsong Fan, Paul Levesque, Jae Kwagh, John Imredy, Jin Zhai, Marc Rogers, Edward Humphries, Robert Kirby, Sonja Stoelzle-Feix, Nina Brinkwirth, Maria Giustina Rotordam, Nadine Becker, Søren Friis, Markus Rapedius, Tom A. Goetze, Tim Strassmaier, George Okeyo, James Kramer, Yuri Kuryshev, Caiyun Wu, Herbert Himmel, Gary R. Mirams, David G. Strauss, Rémi Bardenet, Zhihua Lia. Toxicology and Applied Pharmacology, 394: 114961

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Identification of novel ion channel binders: TRPA1 antagonist case study (Collaboration with Domainex)

Domainex and Metrion Biosciences have formed an alliance to identify new chemical hits against ion-channel targets. Key to this collaboration are Domainex’s experience in hit identification and Metrion Bioscience’s expertise in ion channel screening and pharmacology.

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Identification of novel scorpion venom peptide inhibitors of the Kv1.3 ion channel and their potential as drug discovery leads for human T-cell mediated disease

Activated effector memory T-cells (TEM) have been implicated in the pathogenesis of autoimmune diseases.1 TEM cells express high levels of the voltage-gated potassium channel, Kv1.3, which plays a role in controlling the function of TEM. Inhibition of Kv1.3 reduces the release of pro-inflammatory mediators, inhibits T-cell proliferation and migration to inflamed tissues, and has been shown to ameliorate autoimmune disease symptoms in preclinical animal models.

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Validation of an impedance-based phenotypic screening assay able to detect multiple mechanisms of chronic cardiotoxicity in human stem cell-derived cardiomyocytes

Presentation by Marc Rogers, CSO Metrion Biosciences, Nanion technologies Exhibitor session, 2020 Biophysical Society meeting, San Diego USA.

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