{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T19:38:39Z","timestamp":1777837119009,"version":"3.51.4"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100010166","name":"Xiamen Municipal Bureau of Science and Technology","doi-asserted-by":"publisher","award":["3502Z20194072"],"award-info":[{"award-number":["3502Z20194072"]}],"id":[{"id":"10.13039\/100010166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970283"],"award-info":[{"award-number":["81970283"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2021,11]]},"DOI":"10.1016\/j.ejphar.2021.174441","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T10:45:21Z","timestamp":1630320321000},"page":"174441","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Mechanisms of gefitinib-induced QT prolongation"],"prefix":"10.1016","volume":"910","author":[{"given":"Ling-Jun","family":"Jie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-Da","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He-Qiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua-Bin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fa-Guang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian-Li","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Le","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gui-Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin-Ni","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2021.174441_bib1","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1161\/01.CIR.0000048189.58449.F7","article-title":"Spironolactone and its main metabolite, canrenoic acid, block human ether-a-go-go-related gene channels","volume":"107","author":"Caballero","year":"2003","journal-title":"Circulation"},{"key":"10.1016\/j.ejphar.2021.174441_bib2","doi-asserted-by":"crossref","first-page":"H1757","DOI":"10.1152\/ajpheart.00753.2003","article-title":"A rapidly activating delayed rectifier K+ current regulates pacemaker activity in adult mouse sinoatrial node cells","volume":"286","author":"Clark","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"10.1016\/j.ejphar.2021.174441_bib3","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.1111\/bph.12856","article-title":"Experimental design and analysis and their reporting: new guidance for publication in BJP","volume":"172","author":"Curtis","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174441_bib4","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1002\/ijc.25516","article-title":"Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008","volume":"127","author":"Ferlay","year":"2010","journal-title":"Int. J. Canc."},{"key":"10.1016\/j.ejphar.2021.174441_bib5","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1172\/JCI58227","article-title":"Decreased cardiac L-type Ca(2)(+) channel activity induces hypertrophy and heart failure in mice","volume":"122","author":"Goonasekera","year":"2012","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ejphar.2021.174441_bib6","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1124\/jpet.105.098103","article-title":"Molecular determinants of cocaine block of human ether-a-go-go-related gene potassium channels","volume":"317","author":"Guo","year":"2006","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejphar.2021.174441_bib7","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.ahj.2007.01.040","article-title":"Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes","volume":"153","author":"Gupta","year":"2007","journal-title":"Am. Heart J."},{"key":"10.1016\/j.ejphar.2021.174441_bib8","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.vascn.2005.03.003","article-title":"Cardiovascular parameters in anaesthetized Guinea pigs: a safety pharmacology screening model","volume":"52","author":"Hauser","year":"2005","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"10.1016\/j.ejphar.2021.174441_bib9","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/bph.13679","article-title":"Clemizole hydrochloride blocks cardiac potassium currents stably expressed in HEK 293 cells","volume":"174","author":"Jie","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174441_bib10","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1161\/CIRCULATIONAHA.105.550111","article-title":"Restricting excessive cardiac action potential and QT prolongation: a vital role for IKs in human ventricular muscle","volume":"112","author":"Jost","year":"2005","journal-title":"Circulation"},{"key":"10.1016\/j.ejphar.2021.174441_bib11","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1124\/mol.105.020990","article-title":"Molecular determinants of HERG channel block","volume":"69","author":"Kamiya","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174441_bib12","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/bjc.2015.82","article-title":"Incidence and relevance of QTc-interval prolongation caused by tyrosine kinase inhibitors","volume":"112","author":"Kloth","year":"2015","journal-title":"Br. J. Canc."},{"key":"10.1016\/j.ejphar.2021.174441_bib13","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/bjc.2015.82","article-title":"Incidence and relevance of QTc-interval prolongation caused by tyrosine kinase inhibitors","volume":"112","author":"Kloth","year":"2015","journal-title":"Br. J. Canc."},{"key":"10.1016\/j.ejphar.2021.174441_bib14","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/j.1742-7843.2010.00556.x","article-title":"Electrophysiological effects of the anti-cancer drug lapatinib on cardiac repolarization","volume":"107","author":"Lee","year":"2010","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"10.1016\/j.ejphar.2021.174441_bib15","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s10637-006-5269-2","article-title":"Binding of gefitinib, an inhibitor of epidermal growth factor receptor-tyrosine kinase, to plasma proteins and blood cells: in vitro and in cancer patients","volume":"24","author":"Li","year":"2006","journal-title":"Invest. N. Drugs"},{"key":"10.1016\/j.ejphar.2021.174441_bib16","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1200\/JCO.2012.45.3753","article-title":"Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies","volume":"31","author":"Li","year":"2013","journal-title":"J. Clin. Oncol. : official journal of the American Society of Clinical Oncology"},{"key":"10.1016\/j.ejphar.2021.174441_bib17","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.phrs.2015.12.012","article-title":"SKF-96365 blocks human ether-a-go-go-related gene potassium channels stably expressed in HEK 293 cells","volume":"104","author":"Liu","year":"2016","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.ejphar.2021.174441_bib18","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1056\/NEJMoa040938","article-title":"Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib","volume":"350","author":"Lynch","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejphar.2021.174441_bib19","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.vascn.2015.05.007","article-title":"QT interval correction assessment in the anesthetized Guinea pig","volume":"75","author":"Morissette","year":"2015","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"10.1016\/j.ejphar.2021.174441_bib20","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1080\/02841860903229124","article-title":"Cardiotoxicity induced by tyrosine kinase inhibitors","volume":"48","author":"Orphanos","year":"2009","journal-title":"Acta Oncol."},{"key":"10.1016\/j.ejphar.2021.174441_bib21","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1200\/JCO.2012.42.9829","article-title":"New targetable oncogenes in non-small-cell lung cancer","volume":"31","author":"Oxnard","year":"2013","journal-title":"J. Clin. Oncol. : official journal of the American Society of Clinical Oncology"},{"key":"10.1016\/j.ejphar.2021.174441_bib22","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S0008-6363(02)00846-5","article-title":"Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development","volume":"58","author":"Redfern","year":"2003","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.ejphar.2021.174441_bib23","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ctrv.2007.07.019","article-title":"Molecular-targeted therapies: lessons from years of clinical development","volume":"34","author":"Rosa","year":"2008","journal-title":"Canc. Treat Rev."},{"key":"10.1016\/j.ejphar.2021.174441_bib24","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1183\/09059180.00008413","article-title":"First-line treatment of EGFR-mutated nonsmall cell lung cancer: critical review on study methodology","volume":"23","author":"Sebastian","year":"2014","journal-title":"Eur. Respir. Rev. : an official journal of the European Respiratory Society"},{"key":"10.1016\/j.ejphar.2021.174441_bib25","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1200\/JCO.2006.07.3585","article-title":"Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer","volume":"25","author":"Sequist","year":"2007","journal-title":"J. Clin. Oncol. : official journal of the American Society of Clinical Oncology"},{"key":"10.1016\/j.ejphar.2021.174441_bib26","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1200\/JCO.2012.44.5353","article-title":"ALK in lung cancer: past, present, and future","volume":"31","author":"Shaw","year":"2013","journal-title":"J. Clin. Oncol. : official journal of the American Society of Clinical Oncology"},{"key":"10.1016\/j.ejphar.2021.174441_bib27","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/379833a0","article-title":"The inward rectification mechanism of the HERG cardiac potassium channel","volume":"379","author":"Smith","year":"1996","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2021.174441_bib28","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1085\/jgp.107.5.611","article-title":"Fast inactivation causes rectification of the IKr channel","volume":"107","author":"Spector","year":"1996","journal-title":"J. Gen. Physiol."},{"key":"10.1016\/j.ejphar.2021.174441_bib29","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.yjmcc.2003.10.017","article-title":"Mesoridazine: an open-channel blocker of human ether-a-go-go-related gene K+ channel","volume":"36","author":"Su","year":"2004","journal-title":"J. Mol. Cell. Cardiol."},{"key":"10.1016\/j.ejphar.2021.174441_bib30","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1248\/bpb.29.827","article-title":"Characterization of the halothane-anesthetized Guinea-pig heart as a model to detect the K+ channel blocker-induced QT-interval prolongation","volume":"29","author":"Takahara","year":"2006","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.ejphar.2021.174441_bib32","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0160-5402(89)90015-6","article-title":"An improved method to correct the QT interval of the electrocardiogram for changes in heart rate","volume":"22","author":"Van de Water","year":"1989","journal-title":"J. Pharmacol. Methods"},{"key":"10.1016\/j.ejphar.2021.174441_bib33","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1161\/CIRCEP.113.000239","article-title":"Slow delayed rectifier potassium current blockade contributes importantly to drug-induced long QT syndrome","volume":"6","author":"Veerman","year":"2013","journal-title":"Circulation. Arrhythmia and electrophysiology"},{"key":"10.1016\/j.ejphar.2021.174441_bib34","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1161\/01.CIR.99.18.2466","article-title":"Effects of IKr and IKs heterogeneity on action potential duration and its rate dependence: a simulation study","volume":"99","author":"Viswanathan","year":"1999","journal-title":"Circulation"},{"key":"10.1016\/j.ejphar.2021.174441_bib35","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0031906","article-title":"A novel classification of lung cancer into molecular subtypes","volume":"7","author":"West","year":"2012","journal-title":"PloS One"},{"key":"10.1016\/j.ejphar.2021.174441_bib36","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1046\/j.1540-8167.2004.03632.x","article-title":"Electrophysiologic effects of nicorandil on the Guinea pig long QT1 syndrome model","volume":"15","author":"Yang","year":"2004","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"10.1016\/j.ejphar.2021.174441_bib37","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1378\/chest.128.1.452","article-title":"Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003","volume":"128","author":"Yang","year":"2005","journal-title":"Chest"},{"key":"10.1016\/j.ejphar.2021.174441_bib38","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1073\/pnas.0709662105","article-title":"The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP","volume":"105","author":"Yun","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.ejphar.2021.174441_bib39","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1161\/01.RES.84.9.989","article-title":"Mechanism of block and identification of the verapamil binding domain to HERG potassium channels","volume":"84","author":"Zhang","year":"1999","journal-title":"Circ. Res."},{"key":"10.1016\/j.ejphar.2021.174441_bib40","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1111\/j.1476-5381.2010.00916.x","article-title":"The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide directly blocks human ether a-go-go-related gene potassium channels stably expressed in human embryonic kidney 293 cells","volume":"161","author":"Zhang","year":"2010","journal-title":"Br. J. Pharmacol."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921005951?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921005951?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:16:38Z","timestamp":1762143398000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299921005951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11]]},"references-count":39,"alternative-id":["S0014299921005951"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174441","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2021,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mechanisms of gefitinib-induced QT prolongation","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174441","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":"174441"}}