{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T23:31:14Z","timestamp":1788564674870,"version":"build-2803163510"},"reference-count":32,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100002888","name":"Beijing Municipal Commission of Education","doi-asserted-by":"publisher","award":["KM202010858002"],"award-info":[{"award-number":["KM202010858002"]}],"id":[{"id":"10.13039\/501100002888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology"],"published-print":{"date-parts":[[2021,6]]},"DOI":"10.1016\/j.tox.2021.152822","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T11:40:12Z","timestamp":1622202012000},"page":"152822","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"special_numbering":"C","title":["Computational and experimental studies on the inhibitory mechanism of hydroxychloroquine on hERG"],"prefix":"10.1016","volume":"458","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9211-3760","authenticated-orcid":false,"given":"Ran","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tox.2021.152822_bib0005","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2020.138996","article-title":"Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as coronavirus disease 2019 (COVID-19) pandemic: a global health emergency","volume":"730","author":"Acter","year":"2020","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.tox.2021.152822_bib0010","doi-asserted-by":"crossref","DOI":"10.1016\/j.autneu.2020.102647","article-title":"A novel role of cardiac inwardly rectifying potassium channels explaining autonomic cardiovascular dysfunctions in a cuprizone-induced mouse model of multiple sclerosis","volume":"225","author":"Akyuz","year":"2020","journal-title":"Auton. Neurosci."},{"key":"10.1016\/j.tox.2021.152822_bib0015","doi-asserted-by":"crossref","DOI":"10.1016\/j.cej.2020.126279","article-title":"Degradation of hydroxychloroquine by electrochemical advanced oxidation processes","volume":"402","author":"Bensalah","year":"2020","journal-title":"Chem. Eng. J."},{"issue":"4","key":"10.1016\/j.tox.2021.152822_bib0020","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2019.e01429","article-title":"Functional and pharmacological characterization of an S5 domain hERG mutation associated with short QT syndrome","volume":"5","author":"Butler","year":"2019","journal-title":"Heliyon"},{"issue":"2","key":"10.1016\/j.tox.2021.152822_bib0025","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.drudis.2019.11.005","article-title":"Human ether-\u00e0-go-go-related potassium channel: exploring SAR to improve drug design","volume":"25","author":"Cavalluzzi","year":"2020","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.tox.2021.152822_bib0030","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.3389\/fphar.2020.01091","article-title":"Evidence for the effectiveness of remdesivir (GS-5734), a nucleoside-analog antiviral drug in the inhibition of I K(M) or I K(DR) and in the stimulation of I MEP","volume":"11","author":"Chang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.tox.2021.152822_bib0035","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.yjmcc.2019.07.012","article-title":"Potent hERG channel inhibition by sarizotan, an investigative treatment for Rett Syndrome","volume":"135","author":"Cheng","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"issue":"3","key":"10.1016\/j.tox.2021.152822_bib0040","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jphs.2019.08.001","article-title":"Electrophysiological characterization of a small molecule activator on human ether-a-go-go-related gene (hERG) potassium channel","volume":"140","author":"Dong","year":"2019","journal-title":"J. Pharmacol. Sci."},{"key":"10.1016\/j.tox.2021.152822_bib0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.trac.2020.116082","article-title":"Application of electrophysiological technique in toxicological study: from manual to automated patch-clamp recording","volume":"133","author":"Gao","year":"2020","journal-title":"TrAC Trends Anal. Chem."},{"key":"10.1016\/j.tox.2021.152822_bib0050","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.bpc.2017.06.005","article-title":"Discovery of a new mexiletine-derived agonist of the hERG K+ channel","volume":"229","author":"Gualdani","year":"2017","journal-title":"Biophys. Chem."},{"issue":"1","key":"10.1016\/j.tox.2021.152822_bib0055","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbamem.2020.183448","article-title":"Membrane interactions of non-membrane targeting antibiotics: the case of aminoglycosides, macrolides, and fluoroquinolones","volume":"1863","author":"Khondker","year":"2021","journal-title":"Biochim. Biophys. Acta (BBA) \u2013 Biomembr."},{"issue":"1","key":"10.1016\/j.tox.2021.152822_bib0060","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0014-2999(02)02074-5","article-title":"A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs","volume":"450","author":"Kongsamut","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.tox.2021.152822_bib0065","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ejphar.2019.04.006","article-title":"Effects of cariprazine on hERG 1A and hERG 1A\/3.1 potassium channels","volume":"854","author":"Lee","year":"2019","journal-title":"Eur. J. Pharmacol."},{"issue":"12","key":"10.1016\/j.tox.2021.152822_bib0070","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1016\/j.bpj.2019.07.029","article-title":"Rapid characterization of hERG channel kinetics I: using an automated high-throughput system","volume":"117","author":"Lei","year":"2019","journal-title":"Biophys. J."},{"issue":"5","key":"10.1016\/j.tox.2021.152822_bib0075","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1177\/2042098612454283","article-title":"Drug-induced QT interval prolongation: mechanisms and clinical management","volume":"3","author":"Nachimuthu","year":"2012","journal-title":"Ther. Adv. Drug Saf."},{"key":"10.1016\/j.tox.2021.152822_bib0080","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.resuscitation.2019.04.030","article-title":"Fluoroquinolone use and serious arrhythmias: a nationwide case-crossover study","volume":"139","author":"Porta","year":"2019","journal-title":"Resuscitation"},{"issue":"8","key":"10.1016\/j.tox.2021.152822_bib0085","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.tim.2014.04.007","article-title":"Fluoroquinolone resistance: mechanisms, impact on bacteria, and role in evolutionary success","volume":"22","author":"Redgrave","year":"2014","journal-title":"Trends Microbiol."},{"key":"10.1016\/j.tox.2021.152822_bib0090","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2020.114961","article-title":"A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm","volume":"394","author":"Ridder","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"issue":"4","key":"10.1016\/j.tox.2021.152822_bib0095","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.bpj.2019.10.010","article-title":"hERG function in light of structure","volume":"118","author":"Robertson","year":"2020","journal-title":"Biophys. J."},{"key":"10.1016\/j.tox.2021.152822_bib0100","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.vascn.2015.08.032","article-title":"The source of hERG IC50 values (manual vs. automated patch clamp) may influence in silico modeling","volume":"75","author":"Rohrbacher","year":"2015","journal-title":"J. Pharmacol. Toxicol. Methods"},{"issue":"13","key":"10.1016\/j.tox.2021.152822_bib0105","doi-asserted-by":"crossref","first-page":"3848","DOI":"10.1016\/j.bmcl.2013.04.074","article-title":"The synergic modeling for the binding of fluoroquinolone antibiotics to the hERG potassium channel","volume":"23","author":"Ryu","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"7","key":"10.1016\/j.tox.2021.152822_bib0110","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.jacep.2020.05.037","article-title":"Inhibition of human ether-a-go-go-related gene (hERG) potassium current by the novel sotalol analogue, soestalol","volume":"6","author":"Shugg","year":"2020","journal-title":"JACC Clin. Electrophysiol."},{"key":"10.1016\/j.tox.2021.152822_bib0115","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2020.104176","article-title":"Design and synthesis of novel desfluoroquinolone-aminopyrimidine hybrids as potent anti-MRSA agents with low hERG activity","volume":"103","author":"Song","year":"2020","journal-title":"Bioorg. Chem."},{"issue":"3","key":"10.1016\/j.tox.2021.152822_bib0120","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.hroo.2020.06.002","article-title":"QT interval and arrhythmic safety of hydroxychloroquine monotherapy in coronavirus disease 2019","volume":"1","author":"Sridhar","year":"2020","journal-title":"Heart Rhythm O2"},{"key":"10.1016\/j.tox.2021.152822_bib0125","doi-asserted-by":"crossref","DOI":"10.1016\/j.vascn.2020.106743","article-title":"Reliable identification of hERG liability in drug discovery by automated patch clamp","volume":"105","author":"Stoelzle-Feix","year":"2020","journal-title":"J. Pharmacol. Toxicol. Methods"},{"issue":"3","key":"10.1016\/j.tox.2021.152822_bib0130","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1152\/physrev.00036.2011","article-title":"hERG K+ channels: structure, function, and clinical significance","volume":"92","author":"Vandenberg","year":"2012","journal-title":"Physiol. Rev."},{"issue":"3","key":"10.1016\/j.tox.2021.152822_bib0135","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.bmcl.2017.12.020","article-title":"Molecular determinants of loperamide and N-desmethyl loperamide binding in the hERG cardiac K+ channel","volume":"28","author":"Vaz","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"8","key":"10.1016\/j.tox.2021.152822_bib0140","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1016\/j.mayocp.2020.05.005","article-title":"Acute QT interval modifications during hydroxychloroquine-azithromycin treatment in the context of COVID-19 infection","volume":"95","author":"Voisin","year":"2020","journal-title":"Mayo Clin. Proc."},{"issue":"3","key":"10.1016\/j.tox.2021.152822_bib0145","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2017.03.048","article-title":"Cryo-EM structure of the open human Ether-\u00e0-go-go-related K+ channel hERG","volume":"169","author":"Wang","year":"2017","journal-title":"Cell"},{"issue":"2","key":"10.1016\/j.tox.2021.152822_bib0150","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ccep.2016.01.002","article-title":"Molecular basis of cardiac delayed rectifier potassium channel function and pharmacology","volume":"8","author":"Wu","year":"2016","journal-title":"Card. Electrophysiol. Clin."},{"issue":"4","key":"10.1016\/j.tox.2021.152822_bib0155","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0024-3205(03)00296-0","article-title":"Effects of lomefloxacin and norfloxacin on pancreatic \u03b2-cell ATP-sensitive K+ channels","volume":"73","author":"Z\u00fcnkler","year":"2003","journal-title":"Life Sci."},{"issue":"2","key":"10.1016\/j.tox.2021.152822_bib0160","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.tox.2006.09.002","article-title":"Effects of fluoroquinolones on HERG channels and on pancreatic \u03b2-cell ATP-sensitive K+ channels","volume":"228","author":"Z\u00fcnkler","year":"2006","journal-title":"Toxicology"}],"container-title":["Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X21001451?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X21001451?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T23:45:59Z","timestamp":1759535159000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0300483X21001451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":32,"alternative-id":["S0300483X21001451"],"URL":"https:\/\/doi.org\/10.1016\/j.tox.2021.152822","relation":{},"ISSN":["0300-483X"],"issn-type":[{"value":"0300-483X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Computational and experimental studies on the inhibitory mechanism of hydroxychloroquine on hERG","name":"articletitle","label":"Article Title"},{"value":"Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tox.2021.152822","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"152822"}}