{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:44:03Z","timestamp":1792374243715,"version":"4.4.0"},"reference-count":49,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2022,3]]},"DOI":"10.1016\/j.jbc.2022.101731","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T21:59:51Z","timestamp":1644875991000},"page":"101731","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":30,"title":["Zafirlukast inhibits the growth of lung adenocarcinoma via inhibiting TMEM16A channel activity"],"prefix":"10.1016","volume":"298","author":[{"given":"Sai","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fude","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2022.101731_bib1","series-title":"World Cancer Report 2014","author":"Stewart","year":"2014"},{"key":"10.1016\/j.jbc.2022.101731_bib2","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ijc.33588","article-title":"Cancer statistics for the year 2020: An overview","volume":"149","author":"Ferlay","year":"2021","journal-title":"Int. J. Cancer"},{"key":"10.1016\/j.jbc.2022.101731_bib3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.5334\/aogh.2419","article-title":"Global epidemiology of lung cancer","volume":"85","author":"Barta","year":"2019","journal-title":"Ann. Glob. Health"},{"key":"10.1016\/j.jbc.2022.101731_bib4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0136584","article-title":"Inhibition of calcium-activated chloride channel ANO1\/TMEM16A suppresses tumor growth and invasion in human lung cancer","volume":"10","author":"Jia","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.jbc.2022.101731_bib5","doi-asserted-by":"crossref","first-page":"11369","DOI":"10.1073\/pnas.172285799","article-title":"High-resolution mapping of the 11q13 amplicon and identification of a gene, TAOS1, that is amplified and overexpressed in oral cancer cells","volume":"99","author":"Xin","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2022.101731_bib6","doi-asserted-by":"crossref","first-page":"7856","DOI":"10.1002\/jcp.27865","article-title":"Recent advances in TMEM16A: Structure, function, and disease","volume":"234","author":"Ji","year":"2019","journal-title":"J.\u00a0Cell Physiol."},{"key":"10.1016\/j.jbc.2022.101731_bib7","doi-asserted-by":"crossref","first-page":"8698","DOI":"10.1002\/jcp.27529","article-title":"Matrine is a novel inhibitor of the TMEM16A chloride channel with antilung adenocarcinoma effects","volume":"234","author":"Guo","year":"2019","journal-title":"J.\u00a0Cell Physiol."},{"key":"10.1016\/j.jbc.2022.101731_bib8","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1111\/bph.13841","article-title":"Inhibition of transmembrane member 16A calcium-activated chloride channels by natural flavonoids contributes to flavonoid anticancer effects","volume":"174","author":"Zhang","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jbc.2022.101731_bib9","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/nature07313","article-title":"TMEM16A confers receptor-activated calcium-dependent chloride conductance","volume":"455","author":"Yang","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2022.101731_bib10","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1126\/science.1163518","article-title":"TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity","volume":"322","author":"Caputo","year":"2008","journal-title":"Science"},{"key":"10.1016\/j.jbc.2022.101731_bib11","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.cell.2008.09.003","article-title":"Expression cloning of TMEM16A as a calcium-activated chloride channel subunit","volume":"134","author":"Schroeder","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2022.101731_bib12","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0115443","article-title":"Inhibition of TMEM16A expression suppresses growth and invasion in human colorectal cancer cells","volume":"9","author":"Sui","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.jbc.2022.101731_bib13","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/sj.bjc.6605823","article-title":"ANO1 amplification and expression in HNSCC with a high propensity for future distant metastasis and its functions in HNSCC cell lines","volume":"103","author":"Ayoub","year":"2010","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.jbc.2022.101731_bib14","doi-asserted-by":"crossref","first-page":"11029","DOI":"10.1074\/jbc.M114.549188","article-title":"Small molecule-facilitated degradation of ANO1 protein: A new targeting approach for anticancer therapeutics","volume":"289","author":"Bill","year":"2014","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2022.101731_bib15","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1111\/bph.15606","article-title":"Honokiol inhibits proliferation of colorectal cancer cells by targeting anoctamin 1\/TMEM16A Ca(2+) -activated Cl(-) channels","volume":"178","author":"Wang","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jbc.2022.101731_bib16","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1074\/jbc.M110.175109","article-title":"TMEM16A inhibitors reveal TMEM16A as a minor component of calcium-activated chloride channel conductance in airway and intestinal epithelial cells","volume":"286","author":"Namkung","year":"2011","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2022.101731_bib17","doi-asserted-by":"crossref","first-page":"16354","DOI":"10.1073\/pnas.1214596109","article-title":"Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction","volume":"109","author":"Huang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2022.101731_bib18","doi-asserted-by":"crossref","first-page":"108650","DOI":"10.1016\/j.abb.2020.108650","article-title":"Molecular mechanism of CaCCinh-A01 inhibiting TMEM16A channel","volume":"695","author":"Shi","year":"2020","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.jbc.2022.101731_bib19","doi-asserted-by":"crossref","first-page":"101016","DOI":"10.1016\/j.jbc.2021.101016","article-title":"Theaflavin binds to a druggable pocket of TMEM16A channel and inhibits lung adenocarcinoma cell Viability","volume":"297","author":"Shi","year":"2021","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2022.101731_bib20","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.phrs.2017.07.013","article-title":"Drug repurposing in cancer","volume":"124","author":"Sleire","year":"2017","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.jbc.2022.101731_bib21","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/nrd1470","article-title":"Can the pharmaceutical industry reduce attrition rates?","volume":"3","author":"Kola","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.jbc.2022.101731_bib22","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s12943-017-0720-x","article-title":"Cell-specific mechanisms of TMEM16A Ca2+-activated chloride channel in cancer","volume":"16","author":"Wang","year":"2017","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.jbc.2022.101731_bib23","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/nbt.2786","article-title":"Clinical development success rates for investigational drugs","volume":"32","author":"Hay","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.jbc.2022.101731_bib24","first-page":"442","article-title":"The repurposing drugs in oncology (ReDO) Project","volume":"8","author":"Pan","year":"2014","journal-title":"Ecancermedicalscience"},{"key":"10.1016\/j.jbc.2022.101731_bib25","doi-asserted-by":"crossref","first-page":"583","DOI":"10.3389\/fphar.2018.00583","article-title":"DeCoST: A new approach in drug repurposing from control system theory","volume":"9","author":"Nguyen","year":"2018","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jbc.2022.101731_bib26","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1093\/bib\/bbr013","article-title":"Exploiting drug\u2013disease relationships for computational drug repositioning","volume":"12","author":"Dudley","year":"2011","journal-title":"Brief. Bioinform."},{"key":"10.1016\/j.jbc.2022.101731_bib27","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1378\/chest.126.5.1480","article-title":"Zafirlukast treatment for acute asthma: Evaluation in a randomized, double-blind, multicenter trial","volume":"126","author":"Silverman","year":"2004","journal-title":"Chest"},{"key":"10.1016\/j.jbc.2022.101731_bib28","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/j.1476-5381.2010.00730.x","article-title":"Pharmacological characterization of the first potent and selective antagonist at the cysteinyl leukotriene 2 (CysLT(2)) receptor","volume":"160","author":"Wunder","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jbc.2022.101731_bib29","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1164\/ajrccm.150.3.8087328","article-title":"Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. ACCOLATE Asthma Trialists Group","volume":"150","author":"Spector","year":"1994","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.jbc.2022.101731_bib30","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1164\/ajrccm\/141.4_Pt_1.978","article-title":"The preclinical pharmacology of ICI 204,219. A peptide leukotriene antagonist","volume":"141","author":"Krell","year":"1990","journal-title":"Am. Rev. Respir. Dis."},{"key":"10.1016\/j.jbc.2022.101731_bib31","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3389\/fphar.2019.00263","article-title":"Zafirlukast is a dual modulator of human soluble epoxide hydrolase and peroxisome proliferator-activated receptor \u03b3","volume":"10","author":"G\u00f6bel","year":"2019","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jbc.2022.101731_bib32","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/bph.15291","article-title":"Zafirlukast is a broad-spectrum thiol isomerase inhibitor that inhibits thrombosis without altering bleeding times","volume":"178","author":"Holbrook","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jbc.2022.101731_bib33","doi-asserted-by":"crossref","first-page":"C857","DOI":"10.1152\/ajpcell.00281.2019","article-title":"CysLT1 receptor antagonists pranlukast and zafirlukast inhibit LRRC8-mediated volume regulated anion channels independently of the receptor","volume":"317","author":"Figueroa","year":"2019","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"10.1016\/j.jbc.2022.101731_bib34","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aax2518","article-title":"Structure-based mechanism of cysteinyl leukotriene receptor inhibition by antiasthmatic drugs","volume":"5","author":"Luginina","year":"2019","journal-title":"Sci. Adv."},{"key":"10.1016\/j.jbc.2022.101731_bib35","doi-asserted-by":"crossref","first-page":"104721","DOI":"10.1016\/j.phrs.2020.104721","article-title":"Arctigenin, a novel TMEM16A inhibitor for lung adenocarcinoma therapy","volume":"155","author":"Guo","year":"2020","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.jbc.2022.101731_bib36","doi-asserted-by":"crossref","first-page":"643489","DOI":"10.3389\/fphar.2021.643489","article-title":"Inhibition of TMEM16A by natural product silibinin: Potential lead compounds for treatment of lung adenocarcinoma","volume":"12","author":"Guo","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jbc.2022.101731_bib37","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.csbj.2020.03.015","article-title":"Recent progress in structural studies on TMEM16A channel","volume":"18","author":"Shi","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"10.1016\/j.jbc.2022.101731_bib38","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nature24652","article-title":"Activation mechanism of the calcium-activated chloride channel TMEM16A revealed by cryo-EM","volume":"552","author":"Paulino","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2022.101731_bib39","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology modelling of protein structures and complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jbc.2022.101731_bib40","doi-asserted-by":"crossref","first-page":"D313","DOI":"10.1093\/nar\/gkw1132","article-title":"The SWISS-MODEL Repository-new features and functionality","volume":"45","author":"Bienert","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jbc.2022.101731_bib41","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.jbc.2022.101731_bib42","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.jbc.2022.101731_bib43","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1002\/jcc.21287","article-title":"CHARMM: The biomolecular simulation program","volume":"30","author":"Brooks","year":"2009","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.jbc.2022.101731_bib44","series-title":"Amber 2016","author":"Case","year":"2016"},{"key":"10.1016\/j.jbc.2022.101731_bib45","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1021\/ct400751u","article-title":"Taking into account the ion-induced dipole interaction in the nonbonded model of ions","volume":"10","author":"Li","year":"2014","journal-title":"J.\u00a0Chem. Theory Comput."},{"key":"10.1016\/j.jbc.2022.101731_bib46","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1021\/ct400146w","article-title":"Rational design of Particle Mesh Ewald compatible Lennard-Jones parameters for\u00a0+2 metal cations in explicit solvent","volume":"9","author":"Li","year":"2013","journal-title":"J.\u00a0Chem. Theory Comput."},{"key":"10.1016\/j.jbc.2022.101731_bib47","series-title":"Gaussian 03","author":"Frisch","year":"2003"},{"key":"10.1016\/j.jbc.2022.101731_bib48","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jcc.22885","article-title":"Multiwfn: A multifunctional wavefunction analyzer","volume":"33","author":"Tian","year":"2012","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.jbc.2022.101731_bib49","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J.\u00a0Mol. Graph."}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925822001715?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925822001715?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:27:54Z","timestamp":1758241674000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925822001715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["S0021925822001715"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2022.101731","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2022,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Zafirlukast inhibits the growth of lung adenocarcinoma via inhibiting TMEM16A channel activity","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2022.101731","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"101731"}}