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Research Article

A High-Throughput HERG Potassium Channel Function Assay: An Old Assay with a New Look

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Pages 177-191 | Published online: 04 Aug 2002

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Calum A MacRae. (2010) Cardiac arrhythmia: in vivo screening in the zebrafish to overcome complexity in drug discovery. Expert Opinion on Drug Discovery 5:7, pages 619-632.
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Phillip J Stansfeld, Michael J Sutcliffe & John S Mitcheson. (2006) Molecular mechanisms for drug interactions with hERG that cause long QT syndrome. Expert Opinion on Drug Metabolism & Toxicology 2:1, pages 81-94.
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Articles from other publishers (56)

Taeho Kim, Kee-Choo Chung & Hwangseo Park. (2023) Derivation of Highly Predictive 3D-QSAR Models for hERG Channel Blockers Based on the Quantum Artificial Neural Network Algorithm. Pharmaceuticals 16:11, pages 1509.
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Aziza El Harchi & Jules C. Hancox. (2023) hERG agonists pose challenges to web-based machine learning methods for prediction of drug-hERG channel interaction. Journal of Pharmacological and Toxicological Methods 123, pages 107293.
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Hongsong Feng & Guo-Wei Wei. (2023) Virtual screening of DrugBank database for hERG blockers using topological Laplacian-assisted AI models. Computers in Biology and Medicine 153, pages 106491.
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Mengyi Shan, Chen Jiang, Lu‐Ping Qin & Gang Cheng. (2022) A Review of Computational Methods in Predicting hERG Channel Blockers. ChemistrySelect 7:31.
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Hamideh P Fallah, Ekta Ahuja, Haoquan Lin, Jinlong Qi, Qian He, Shan Gao, Hailong An, Jian Zhang, Yongzhen Xie & Dong Liang. (2022) A Review on the Role of TRP Channels and Their Potential as Drug Targets_An Insight Into the TRP Channel Drug Discovery Methodologies. Frontiers in Pharmacology 13.
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Xudong Zhang, Jun Mao, Min Wei, Yifei Qi & John Z. H. Zhang. (2022) HergSPred: Accurate Classification of hERG Blockers/Nonblockers with Machine-Learning Models. Journal of Chemical Information and Modeling 62:8, pages 1830-1839.
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Jinghua Zhao & Menghang Xia. 2022. High-Throughput Screening Assays in Toxicology. High-Throughput Screening Assays in Toxicology 21 28 .
Nataraj Sekhar Pagadala. (2021) Computational prediction of hERG blockers using homology modelling, molecular docking and QuaSAR studies. Results in Chemistry 3, pages 100101.
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Leela Sarath Kumar Konda, S. Keerthi Praba & Rajendra Kristam. (2019) hERG liability classification models using machine learning techniques. Computational Toxicology 12, pages 100089.
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Reka A. Otvos, Kristina B.M. Still, Govert W. Somsen, August B. Smit & Jeroen Kool. (2019) Drug Discovery on Natural Products: From Ion Channels to nAChRs, from Nature to Libraries, from Analytics to Assays. SLAS Discovery 24:3, pages 362-385.
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Xiao Li, Yuan Zhang, Huanhuan Li & Yong Zhao. (2017) Modeling of the hERG K+ Channel Blockage Using Online Chemical Database and Modeling Environment (OCHEM). Molecular Informatics 36:12, pages 1700074.
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Paul A. Lapchak & John H. Zhang. (2016) The High Cost of Stroke and Stroke Cytoprotection Research. Translational Stroke Research 8:4, pages 307-317.
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Paul A. Lapchak & Paul D. Boitano. 2017. Neuroprotective Therapy for Stroke and Ischemic Disease. Neuroprotective Therapy for Stroke and Ischemic Disease 3 71 .
Hai-bo Yu, Bei-yan Zou, Xiao-liang Wang & Min Li. (2016) Investigation of miscellaneous hERG inhibition in large diverse compound collection using automated patch-clamp assay. Acta Pharmacologica Sinica 37:1, pages 111-123.
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Li Di & Edward H. Kerns. 2016. Drug-Like Properties. Drug-Like Properties 423 432 .
Claire Townsend & Barry S. Brown. (2013) Predicting Drug‐Induced QT Prolongation and Torsades de Pointes: A Review of Preclinical Endpoint Measures. Current Protocols in Pharmacology 61:1.
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Shiva A. Portonovo, Carl S. Salazar & Jacob J. Schmidt. (2012) hERG drug response measured in droplet bilayers. Biomedical Microdevices 15:2, pages 255-259.
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A Wickenden, B Priest & G Erdemli. (2012) Ion channel drug discovery: challenges and future directions. Future Medicinal Chemistry 4:5, pages 661-679.
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Paweł Szymański, Magdalena Markowicz & Elżbieta Mikiciuk-Olasik. (2011) Adaptation of High-Throughput Screening in Drug Discovery—Toxicological Screening Tests. International Journal of Molecular Sciences 13:1, pages 427-452.
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Xiaojing Su, Edmond W.K. Young, Heather A.S. Underkofler, Timothy J. Kamp, Craig T. January & David J. Beebe. (2011) Microfluidic Cell Culture and Its Application in High-Throughput Drug Screening: Cardiotoxicity Assay for hERG Channels. SLAS Discovery 16:1, pages 101-111.
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Ingemar Jacobson, Leif Carlsson & Göran Duker. (2011) Beat-by-beat QT interval variability, but not QT prolongation per se, predicts drug-induced torsades de pointes in the anaesthetised methoxamine-sensitized rabbit. Journal of Pharmacological and Toxicological Methods 63:1, pages 40-46.
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Xi-Ping HuangThomas ManganoSandy HufeisenVincent SetolaBryan L. Roth. (2010) Identification of Human Ether-à-go-go Related Gene Modulators by Three Screening Platforms in an Academic Drug-Discovery Setting . ASSAY and Drug Development Technologies 8:6, pages 727-742.
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Terry R. BridalMichael MargulisXin WangMichael DonioSteve Sorota. (2010) Comparison of Human Ether-à-go-go Related Gene Screening Assays Based on IonWorks Quattro and Thallium Flux . ASSAY and Drug Development Technologies 8:6, pages 755-765.
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Munikumar R. Doddareddy, Elisabeth C. Klaasse, Shagufta, Adriaan P. IJzerman & Andreas Bender. (2010) Prospective Validation of a Comprehensive In silico hERG Model and its Applications to Commercial Compound and Drug Databases. ChemMedChem 5:5, pages 716-729.
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Vito G. Sasseville, William R. Foster & Bruce D. Car. 2009. Evaluation of Drug Candidates for Preclinical Development. Evaluation of Drug Candidates for Preclinical Development 219 252 .
Khuram W. Chaudhary & Barry S. Brown. 2009. Evaluation of Drug Candidates for Preclinical Development. Evaluation of Drug Candidates for Preclinical Development 253 279 .
Steven A. Titus, Daniel Beacham, Sampada A. Shahane, Noel Southall, Menghang Xia, Ruili Huang, Elizabeth Hooten, Yong Zhao, Louie Shou, Christopher P. Austin & Wei Zheng. (2009) A new homogeneous high-throughput screening assay for profiling compound activity on the human ether-a-go-go-related gene channel. Analytical Biochemistry 394:1, pages 30-38.
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Dimitri Mikhailov, Martin Traebert, Qiang Lu, Steven Whitebread & William Egan. 2009. Hit and Lead Profiling. Hit and Lead Profiling 387 413 .
Jerzy Karczewski, Jixin Wang, Stefanie A. Kane, Laszlo Kiss, Kenneth S. Koblan, J. Christopher Culberson & Robert H. Spencer. (2009) Analogs of MK-499 are differentially affected by a mutation in the S6 domain of the hERG K+ channel. Biochemical Pharmacology 77:10, pages 1602-1611.
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Sebastian Polak, Barbara Wiśniowska & Jerzy Brandys. (2008) Collation, assessment and analysis of literature in vitro data on hERG receptor blocking potency for subsequent modeling of drugs' cardiotoxic properties . Journal of Applied Toxicology 29:3, pages 183-206.
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Sitarama B. Gunturi, Kotu Archana, Akash Khandelwal & Ramamurthi Narayanan. (2008) Prediction of hERG Potassium Channel Blockade Using kNN-QSAR and Local Lazy Regression Methods. QSAR & Combinatorial Science 27:11-12, pages 1305-1317.
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Keith A. Houck & Robert J. Kavlock. (2008) Understanding mechanisms of toxicity: Insights from drug discovery research. Toxicology and Applied Pharmacology 227:2, pages 163-178.
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Edward H. Kerns & Li Di. 2008. Drug-like Properties: Concepts, Structure Design and Methods. Drug-like Properties: Concepts, Structure Design and Methods 378 385 .
David J. Diller & Doug W. Hobbs. (2007) Understanding hERG inhibition with QSAR models based on a one-dimensional molecular representation. Journal of Computer-Aided Molecular Design 21:7, pages 379-393.
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David H. Singleton, Helen Boyd, Jill V. Steidl-Nichols, Matt Deacon, Marcel J. de Groot, David Price, David O. Nettleton, Nora K. Wallace, Matthew D. Troutman, Christine Williams & James G. Boyd. (2007) Fluorescently Labeled Analogues of Dofetilide as High-Affinity Fluorescence Polarization Ligands for the Human Ether-a-go-go-Related Gene (hERG) Channel. Journal of Medicinal Chemistry 50:13, pages 2931-2941.
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Matt Deacon, David Singleton, Nikki Szalkai, Rodger Pasieczny, Chris Peacock, David Price, James Boyd, Helen Boyd, Jill V. Steidl-Nichols & Christine Williams. (2007) Early evaluation of compound QT prolongation effects: A predictive 384-well fluorescence polarization binding assay for measuring hERG blockade. Journal of Pharmacological and Toxicological Methods 55:3, pages 255-264.
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Mark D. McBriar, Henry Guzik, Sherry Shapiro, Ruo Xu, Jaroslava Paruchova, John W. Clader, Kim O’Neill, Brian Hawes, Steve Sorota, Michael Margulis, Kristal Tucker, Daniel J. Weston & Kathleen Cox. (2006) Bicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists: Impacting hERG liability via aryl modifications. Bioorganic & Medicinal Chemistry Letters 16:16, pages 4262-4265.
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Tim Hammond & Jean-Pierre Valentin. 2006. The Process of New Drug Discovery and Development, Second Edition. The Process of New Drug Discovery and Development, Second Edition 243 289 .
Han Choe, Kwang Hoon Nah, Soo Nam Lee, Han Sam Lee, Hui Sun Lee, Su Hyun Jo, Chae Hun Leem & Yeon Jin Jang. (2006) A novel hypothesis for the binding mode of HERG channel blockers. Biochemical and Biophysical Research Communications 344:1, pages 72-78.
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Khuram W. ChaudharyJanet M. O'NealZun-Li MoBernard FerminiRobert H. GallavanAnthony Bahinski. (2006) Evaluation of the Rubidium Efflux Assay for Preclinical Identification of hERG Blockade. ASSAY and Drug Development Technologies 4:1, pages 73-82.
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Brian D. Guth. 2006. Drug Discovery and Evaluation. Drug Discovery and Evaluation 61 94 .
Giovanni Cianchetta, Yi Li, Jiesheng Kang, David Rampe, Arnaldo Fravolini, Gabriele Cruciani & Roy J. Vaz. (2005) Predictive models for hERG potassium channel blockers. Bioorganic & Medicinal Chemistry Letters 15:15, pages 3637-3642.
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Arnulf Dorn, Francis Hermann, Andreas Ebneth, Hendrick Bothmann, Gerhard Trube, Klaus Christensen & Christian Apfel. (2005) Evaluation of a High-Throughput Fluorescence Assay Method for hERG Potassium Channel Inhibition. SLAS Discovery 10:4, pages 339-347.
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Michael C. Sanguinetti & John S. Mitcheson. (2005) Predicting drug–hERG channel interactions that cause acquired long QT syndrome. Trends in Pharmacological Sciences 26:3, pages 119-124.
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Steve SorotaXue-Song ZhangMichael MargulisKristal TuckerTony Priestley. (2005) Characterization of a hERG Screen Using the IonWorks HT: Comparison to a hERG Rubidium Efflux Screen. ASSAY and Drug Development Technologies 3:1, pages 47-57.
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Haiyan Sun, Sojin Shikano, Qiaojie Xiong & Min Li. (2004) Function recovery after chemobleaching (FRAC): Evidence for activity silent membrane receptors on cell surface. Proceedings of the National Academy of Sciences 101:48, pages 16964-16969.
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CHRISTINA DAVIE, JEAN PIERRE‐VALENTIN, CHRIS POLLARD, NICK STANDEN, JOHN MITCHESON, PAUL ALEXANDER & BOB THONG. (2004) Comparative Pharmacology of Guinea Pig Cardiac Myocyte and Cloned hERG (I Kr ) Channel . Journal of Cardiovascular Electrophysiology 15:11, pages 1302-1309.
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Gilbert J. Diaz, Katina Daniell, Sandra T. Leitza, Ruth L. Martin, Zhi Su, Jeffrey S. McDermott, Bryan F. Cox & Gary A. Gintant. (2004) The [3H]dofetilide binding assay is a predictive screening tool for hERG blockade and proarrhythmia: Comparison of intact cell and membrane preparations and effects of altering [K+]o. Journal of Pharmacological and Toxicological Methods 50:3, pages 187-199.
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Saman Rezazadeh, J. Christian Hesketh & David Fedida. (2004) Rb+ Flux through hERG Channels Affects the Potency of Channel Blocking Drugs: Correlation with Data Obtained Using a High-Throughput Rb+ Efflux Assay. SLAS Discovery 9:7, pages 588-597.
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Larisa StankovichDavid WicksSasko DespotovskiDong Liang. (2004) Atomic Absorption Spectroscopy in Ion Channel Screening. ASSAY and Drug Development Technologies 2:5, pages 569-574.
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Keith Finlayson, Harry J. Witchel, James McCulloch & John Sharkey. (2004) Acquired QT interval prolongation and HERG: implications for drug discovery and development. European Journal of Pharmacology 500:1-3, pages 129-142.
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Charles A. Blum, Xiaozhang Zheng & Stéphane De Lombaert. (2004) Design, Synthesis, and Biological Evaluation of Substituted 2-Cyclohexyl-4-phenyl-1 H -imidazoles:  Potent and Selective Neuropeptide Y Y5-Receptor Antagonists . Journal of Medicinal Chemistry 47:9, pages 2318-2325.
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Paul B Bennett & Heather R.E Guthrie. (2003) Trends in ion channel drug discovery: advances in screening technologies. Trends in Biotechnology 21:12, pages 563-569.
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Sikander Gill, Raj Gill, Soo Sen Lee, J. Christian Hesketh, David Fedida, Saman Rezazadeh, Larisa Stankovich & Dong Liang. (2003) Flux Assays in High Throughput Screening of Ion Channels in Drug Discovery. ASSAY and Drug Development Technologies 1:5, pages 709-717.
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Clay W Scott, Deidre E Wilkins, Shephali Trivedi & Denis J Crankshaw. (2003) A medium-throughput functional assay of KCNQ2 potassium channels using rubidium efflux and atomic absorption spectrometry. Analytical Biochemistry 319:2, pages 251-257.
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J. Fraser Glickman. (2003) Literature Search and Review. ASSAY and Drug Development Technologies 1:supplement 2, pages 209-214.
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