{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:25:10Z","timestamp":1792211110912,"version":"4.4.0"},"reference-count":76,"publisher":"Rockefeller University Press","issue":"7","license":[{"start":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:00:00Z","timestamp":1717027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP2-GM126898"],"award-info":[{"award-number":["DP2-GM126898"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35-GM153196"],"award-info":[{"award-number":["R35-GM153196"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GMR01-132598"],"award-info":[{"award-number":["GMR01-132598"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["903807"],"award-info":[{"award-number":["903807"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:p>The TMEM16A calcium-activated chloride channel is a promising therapeutic target for various diseases. Niclosamide, an anthelmintic medication, has been considered a TMEM16A inhibitor for treating asthma and chronic obstructive pulmonary disease (COPD) but was recently found to possess broad-spectrum off-target effects. Here, we show that, under physiological Ca2+ (200\u2013500 nM) and voltages, niclosamide acutely potentiates TMEM16A. Our computational and functional characterizations pinpoint a putative niclosamide binding site on the extracellular side of TMEM16A. Mutations in this site attenuate the potentiation. Moreover, niclosamide potentiates endogenous TMEM16A in vascular smooth muscle cells, triggers intracellular calcium increase, and constricts the murine mesenteric artery. Our findings advise caution when considering clinical applications of niclosamide as a TMEM16A inhibitor. The identification of the putative niclosamide binding site provides insights into the mechanism of TMEM16A pharmacological modulation and provides insights into developing specific TMEM16A modulators to treat human diseases.<\/jats:p>","DOI":"10.1085\/jgp.202313460","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T02:20:59Z","timestamp":1716430859000},"update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Niclosamide potentiates TMEM16A and induces vasoconstriction"],"prefix":"10.1085","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5128-1509","authenticated-orcid":true,"given":"Pengfei","family":"Liang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01n9kga30","id-type":"ROR","asserted-by":"publisher"}],"name":"Duke University School of Medicine 1 Department of Biochemistry, , Durham, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3189-0021","authenticated-orcid":true,"given":"Yui Chun S.","family":"Wan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01n9kga30","id-type":"ROR","asserted-by":"publisher"}],"name":"Duke University School of Medicine 1 Department of Biochemistry, , Durham, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1863-8934","authenticated-orcid":true,"given":"Kuai","family":"Yu","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine 2 Department of Cell Biology, , Atlanta, GA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3393-1528","authenticated-orcid":true,"given":"H. Criss","family":"Hartzell","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine 2 Department of Cell Biology, , Atlanta, GA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9521-9328","authenticated-orcid":true,"given":"Huanghe","family":"Yang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01n9kga30","id-type":"ROR","asserted-by":"publisher"}],"name":"Duke University School of Medicine 1 Department of Biochemistry, , Durham, NC,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/01n9kga30","id-type":"ROR","asserted-by":"publisher"}],"name":"Duke University School of Medicine 3 Department of Neurobiology, , Durham, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"key":"2026041423530120700_bib1","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1007\/s12265-015-9616-6","article-title":"Guidelines for the isolation and characterization of murine vascular smooth muscle cells. A report from the international society of cardiovascular translational research","volume":"8","author":"Adhikari","year":"2015","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"2026041423530120700_bib2","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1016\/j.tips.2022.06.006","article-title":"The pharmacology of the TMEM16A channel: Therapeutic opportunities","volume":"43","author":"Al-Hosni","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"2026041423530120700_bib3","doi-asserted-by":"publisher","first-page":"28571","DOI":"10.1074\/jbc.M109.010074","article-title":"TMEM16 proteins produce volume-regulated chloride currents that are reduced in mice lacking TMEM16A","volume":"284","author":"Alma\u00e7a","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2026041423530120700_bib4","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.jare.2021.01.013","article-title":"The diverse roles of TMEM16A Ca2+-activated Cl\u2212 channels in inflammation","volume":"33","author":"Bai","year":"2021","journal-title":"J. Adv. Res."},{"key":"2026041423530120700_bib77","first-page":"1","volume-title":"Calcium in Living Cells","author":"Bers","year":"2010"},{"key":"2026041423530120700_bib5","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1007\/s00424-013-1357-2","article-title":"Cl\u207b channels in smooth muscle cells","volume":"466","author":"Bulley","year":"2014","journal-title":"Pflugers Arch."},{"key":"2026041423530120700_bib6","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.128414","article-title":"Niclosamide repurposed for the treatment of inflammatory airway disease","volume":"4","author":"Cabrita","year":"2019","journal-title":"JCI Insight"},{"key":"2026041423530120700_bib7","doi-asserted-by":"publisher","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":"2026041423530120700_bib8","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.3390\/ijms21072557","article-title":"Pharmacological inhibition and activation of the Ca2+ activated Cl\u2212 channel TMEM16A","volume":"21","author":"Centeio","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2026041423530120700_bib9","doi-asserted-by":"publisher","first-page":"10267","DOI":"10.1021\/bi9009677","article-title":"The anti-helminthic niclosamide inhibits Wnt\/Frizzled1 signaling","volume":"48","author":"Chen","year":"2009","journal-title":"Biochemistry"},{"key":"2026041423530120700_bib10","doi-asserted-by":"publisher","first-page":"102050","DOI":"10.1016\/j.ceca.2019.06.004","article-title":"The multifaceted role of TMEM16A in cancer","volume":"82","author":"Crott\u00e8s","year":"2019","journal-title":"Cell Calcium"},{"key":"2026041423530120700_bib11","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1096\/fba.2020-00035","article-title":"Potentiating TMEM16A does not stimulate airway mucus secretion or bronchial and pulmonary arterial smooth muscle contraction","volume":"2","author":"Danahay","year":"2020","journal-title":"FASEB Bioadv."},{"key":"2026041423530120700_bib12","doi-asserted-by":"publisher","first-page":"1142342","DOI":"10.3389\/fphar.2023.1142342","article-title":"Niclosamide does not modulate airway epithelial function through blocking of the calcium activated chloride channel, TMEM16A","volume":"14","author":"Danahay","year":"2023","journal-title":"Front. Pharmacol."},{"key":"2026041423530120700_bib13","doi-asserted-by":"publisher","first-page":"3118","DOI":"10.1167\/iovs.16-21128","article-title":"Identification of novel G protein-coupled receptor 143 ligands as pharmacologic tools for investigating X-linked ocular albinism","volume":"58","author":"De Filippo","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2026041423530120700_bib14","doi-asserted-by":"publisher","first-page":"3160","DOI":"10.1016\/j.bmc.2005.12.032","article-title":"New insights about HERG blockade obtained from protein modeling, potential energy mapping, and docking studies","volume":"14","author":"Farid","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"2026041423530120700_bib15","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"2026041423530120700_bib16","doi-asserted-by":"publisher","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"key":"2026041423530120700_bib17","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1111\/bph.15995","article-title":"Analysis of inhibitors of the anoctamin-1 chloride channel (transmembrane member 16A, TMEM16A) reveals indirect mechanisms involving alterations in calcium signalling","volume":"180","author":"Genovese","year":"2023","journal-title":"Br. J. Pharmacol."},{"key":"2026041423530120700_bib18","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1007\/s10822-010-9349-1","article-title":"Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution","volume":"24","author":"Greenwood","year":"2010","journal-title":"J. Comput. Aided Mol. Des."},{"key":"2026041423530120700_bib19","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening","volume":"47","author":"Halgren","year":"2004","journal-title":"J. Med. Chem."},{"key":"2026041423530120700_bib20","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1021\/acs.jctc.5b00864","article-title":"OPLS3: A force field providing broad coverage of drug-like small molecules and proteins","volume":"12","author":"Harder","year":"2016","journal-title":"J. Chem. Theor. Comput."},{"key":"2026041423530120700_bib21","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1080\/19336950.2021.1975411","article-title":"Molecular mechanisms of activation and regulation of ANO1-Encoded Ca2+-Activated Cl\u2212 channels","volume":"15","author":"Hawn","year":"2021","journal-title":"Channels"},{"key":"2026041423530120700_bib22","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1089\/adt.2019.962","article-title":"Development of a QPatch-automated electrophysiology assay for identifying TMEM16A small-molecule inhibitors","volume":"18","author":"Henckels","year":"2020","journal-title":"Assay Drug Dev. Technol."},{"key":"2026041423530120700_bib23","doi-asserted-by":"publisher","first-page":"21413","DOI":"10.1073\/pnas.0911935106","article-title":"Studies on expression and function of the TMEM16A calcium-activated chloride channel","volume":"106","author":"Huang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026041423530120700_bib24","doi-asserted-by":"publisher","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. USA"},{"key":"2026041423530120700_bib25","doi-asserted-by":"publisher","first-page":"770450","DOI":"10.3389\/fphys.2021.770450","article-title":"Calcium-dependent ion channels and the regulation of arteriolar myogenic tone","volume":"12","author":"Jackson","year":"2021","journal-title":"Front. Physiol."},{"key":"2026041423530120700_bib26","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/S0022-2836(02)00470-9","article-title":"On the role of the crystal environment in determining protein side-chain conformations","volume":"320","author":"Jacobson","year":"2002","journal-title":"J. Mol. Biol."},{"key":"2026041423530120700_bib27","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1002\/prot.10613","article-title":"A hierarchical approach to all-atom protein loop prediction","volume":"55","author":"Jacobson","year":"2004","journal-title":"Proteins"},{"key":"2026041423530120700_bib28","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/s42003-021-01782-2","article-title":"Specific PIP2 binding promotes calcium activation of TMEM16A chloride channels","volume":"4","author":"Jia","year":"2021","journal-title":"Commun. Biol."},{"key":"2026041423530120700_bib29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002976","article-title":"Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects","volume":"8","author":"Jurgeit","year":"2012","journal-title":"PLoS Pathog."},{"key":"2026041423530120700_bib30","doi-asserted-by":"publisher","first-page":"30787","DOI":"10.1073\/pnas.2014520117","article-title":"Allosteric modulation of alternatively spliced Ca2+-activated Cl\u2212 channels TMEM16A by PI(4,5)P2 and CaMKII","volume":"117","author":"Ko","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026041423530120700_bib31","doi-asserted-by":"publisher","DOI":"10.1172\/JCI154118","article-title":"The Ca2+-gated channel TMEM16A amplifies capillary pericyte contraction and reduces cerebral blood flow after ischemia","volume":"132","author":"Korte","year":"2022","journal-title":"J. Clin. Invest."},{"key":"2026041423530120700_bib32","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3389\/fphar.2019.00003","article-title":"TMEM16A in cystic fibrosis: Activating or inhibiting?","volume":"10","author":"Kunzelmann","year":"2019","journal-title":"Front. Pharmacol."},{"key":"2026041423530120700_bib33","doi-asserted-by":"publisher","first-page":"3769","DOI":"10.1038\/s41467-019-11784-8","article-title":"Molecular basis of PIP2-dependent regulation of the Ca2+-activated chloride channel TMEM16A","volume":"10","author":"Le","year":"2019","journal-title":"Nat. Commun."},{"key":"2026041423530120700_bib34","doi-asserted-by":"publisher","first-page":"787773","DOI":"10.3389\/fphys.2021.787773","article-title":"Gating and regulatory mechanisms of TMEM16 ion channels and scramblases","volume":"12","author":"Le","year":"2021","journal-title":"Front. Physiol."},{"key":"2026041423530120700_bib35","doi-asserted-by":"publisher","first-page":"108570","DOI":"10.1016\/j.celrep.2020.108570","article-title":"An additional Ca2+ binding site allosterically controls TMEM16A activation","volume":"33","author":"Le","year":"2020","journal-title":"Cell Rep."},{"key":"2026041423530120700_bib36","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1038\/s41467-019-09778-7","article-title":"An inner activation gate controls TMEM16F phospholipid scrambling","volume":"10","author":"Le","year":"2019","journal-title":"Nat. Commun."},{"key":"2026041423530120700_bib37","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1086\/680189","article-title":"Molecular and functional significance of Ca(2+)-activated Cl(\u2212) channels in pulmonary arterial smooth muscle","volume":"5","author":"Leblanc","year":"2015","journal-title":"Pulm. Circ."},{"key":"2026041423530120700_bib38","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.67858","article-title":"Genetically engineered mice for combinatorial cardiovascular optobiology","volume":"10","author":"Lee","year":"2021","journal-title":"Elife"},{"key":"2026041423530120700_bib39","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.phrs.2016.11.008","article-title":"Niclosamide ethanolamine inhibits artery constriction","volume":"115","author":"Li","year":"2017","journal-title":"Pharmacol. Res."},{"key":"2026041423530120700_bib40","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.202012704","article-title":"Molecular underpinning of intracellular pH regulation on TMEM16F","volume":"153","author":"Liang","year":"2021","journal-title":"J. Gen. Physiol."},{"key":"2026041423530120700_bib41","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1016\/j.apsb.2020.12.003","article-title":"The Ca2+-activated chloride channel ANO1\/TMEM16A: An emerging therapeutic target for epithelium-originated diseases?","volume":"11","author":"Liu","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"2026041423530120700_bib42","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1161\/HYPERTENSIONAHA.116.08874","article-title":"TMEM16A contributes to endothelial dysfunction by facilitating Nox2 NADPH oxidase-derived reactive oxygen species generation in hypertension","volume":"69","author":"Ma","year":"2017","journal-title":"Hypertension"},{"key":"2026041423530120700_bib43","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3389\/fphar.2019.00051","article-title":"Drug repurposing: The anthelmintics niclosamide and nitazoxanide are potent TMEM16A antagonists that fully bronchodilate airways","volume":"10","author":"Miner","year":"2019","journal-title":"Front. Pharmacol."},{"key":"2026041423530120700_bib44","doi-asserted-by":"publisher","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. Biol. Chem."},{"key":"2026041423530120700_bib45","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1021\/ct100578z","article-title":"PROPKA3: Consistent treatment of internal and surface residues in empirical pKa predictions","volume":"7","author":"Olsson","year":"2011","journal-title":"J. Chem. Theor. Comput."},{"key":"2026041423530120700_bib46","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.3390\/ijms23031085","article-title":"Airway delivery of hydrogel-encapsulated niclosamide for the treatment of inflammatory airway disease","volume":"23","author":"Ousingsawat","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2026041423530120700_bib47","doi-asserted-by":"publisher","first-page":"1800965","DOI":"10.1183\/13993003.00965-2018","article-title":"Targeting TMEM16A to reverse vasoconstriction and remodelling in idiopathic pulmonary arterial hypertension","volume":"53","author":"Papp","year":"2019","journal-title":"Eur. Respir. J."},{"key":"2026041423530120700_bib48","doi-asserted-by":"publisher","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":"2026041423530120700_bib49","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1152\/physrev.00039.2011","article-title":"Structure and function of TMEM16 proteins (anoctamins)","volume":"94","author":"Pedemonte","year":"2014","journal-title":"Physiol. Rev."},{"key":"2026041423530120700_bib50","doi-asserted-by":"publisher","first-page":"3547","DOI":"10.1073\/pnas.1502291112","article-title":"Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels","volume":"112","author":"Peters","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026041423530120700_bib51","doi-asserted-by":"publisher","first-page":"3616","DOI":"10.1093\/brain\/awad172","article-title":"Rare variants in ANO1, encoding a calcium-activated chloride channel, predispose to moyamoya disease","volume":"146","author":"Pinard","year":"2023","journal-title":"Brain"},{"key":"2026041423530120700_bib52","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/s41467-017-00429-3","article-title":"Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance","volume":"8","author":"Rode","year":"2017","journal-title":"Nat. Commun."},{"key":"2026041423530120700_bib53","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"2026041423530120700_bib54","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"2026041423530120700_bib55","doi-asserted-by":"publisher","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":"2026041423530120700_bib56","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0155771","article-title":"Ani9, A novel potent small-molecule ANO1 inhibitor with negligible effect on ANO2","volume":"11","author":"Seo","year":"2016","journal-title":"PLoS One"},{"key":"2026041423530120700_bib57","doi-asserted-by":"publisher","first-page":"50328","DOI":"10.3791\/50328","article-title":"Assessing murine resistance artery function using pressure myography","author":"Shahid","year":"2013","journal-title":"J. Vis. Exp."},{"key":"2026041423530120700_bib58","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1007\/s10822-007-9133-z","article-title":"Epik: A software program for pK( a ) prediction and protonation state generation for drug-like molecules","volume":"21","author":"Shelley","year":"2007","journal-title":"J. Comput. Aided Mol. Des."},{"key":"2026041423530120700_bib59","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/j.1747-0285.2005.00327.x","article-title":"Use of an induced fit receptor structure in virtual screening","volume":"67","author":"Sherman","year":"2006","journal-title":"Chem. Biol. Drug Des."},{"key":"2026041423530120700_bib60","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1021\/jm050540c","article-title":"Novel procedure for modeling ligand\/receptor induced fit effects","volume":"49","author":"Sherman","year":"2006","journal-title":"J. Med. Chem."},{"key":"2026041423530120700_bib61","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1021\/ct200133y","article-title":"Improved treatment of ligands and coupling effects in empirical calculation and rationalization of pKa values","volume":"7","author":"S\u00f8ndergaard","year":"2011","journal-title":"J. Chem. Theor. Comput."},{"key":"2026041423530120700_bib62","doi-asserted-by":"publisher","first-page":"113841","DOI":"10.1016\/j.bbr.2022.113841","article-title":"Conditional deletion of TMEM16A in cholinergic neurons of the medial habenula induces anhedonic-like behavior in mice","volume":"426","author":"Song","year":"2022","journal-title":"Behav. Brain Res."},{"key":"2026041423530120700_bib63","doi-asserted-by":"publisher","first-page":"5213","DOI":"10.1073\/pnas.1421507112","article-title":"Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in sensory neurons","volume":"112","author":"Takayama","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026041423530120700_bib64","doi-asserted-by":"publisher","first-page":"12556","DOI":"10.1074\/jbc.RA118.007128","article-title":"Phosphatidylinositol 4,5-bisphosphate (PIP2) and Ca2+ are both required to open the Cl\u2212 channel TMEM16A","volume":"294","author":"Tembo","year":"2019","journal-title":"J. Biol. Chem."},{"key":"2026041423530120700_bib65","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02772","article-title":"A comprehensive search for calcium binding sites critical for TMEM16A calcium-activated chloride channel activity","volume":"3","author":"Tien","year":"2014","journal-title":"Elife"},{"key":"2026041423530120700_bib66","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/s41598-018-36564-0","article-title":"Smoothelin-like 1 deletion enhances myogenic reactivity of mesenteric arteries with alterations in PKC and myosin phosphatase signaling","volume":"9","author":"Turner","year":"2019","journal-title":"Sci. Rep."},{"key":"2026041423530120700_bib67","doi-asserted-by":"publisher","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":"2026041423530120700_bib68","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1146\/annurev-physiol-022516-034031","article-title":"Anoctamins\/TMEM16 proteins: Chloride channels flirting with lipids and extracellular vesicles","volume":"79","author":"Whitlock","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"2026041423530120700_bib69","doi-asserted-by":"publisher","first-page":"751008","DOI":"10.3389\/fphys.2021.751008","article-title":"Calcium-activated chloride channels in myometrial and vascular smooth muscle","volume":"12","author":"Wray","year":"2021","journal-title":"Front. Physiol."},{"key":"2026041423530120700_bib70","doi-asserted-by":"publisher","first-page":"8891","DOI":"10.1073\/pnas.1102147108","article-title":"Voltage- and calcium-dependent gating of TMEM16A\/Ano1 chloride channels are physically coupled by the first intracellular loop","volume":"108","author":"Xiao","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026041423530120700_bib71","doi-asserted-by":"publisher","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":"2026041423530120700_bib72","doi-asserted-by":"publisher","first-page":"19952","DOI":"10.1073\/pnas.1904012116","article-title":"A network of phosphatidylinositol 4,5-bisphosphate binding sites regulates gating of the Ca2+-activated Cl\u2212 channel ANO1 (TMEM16A)","volume":"116","author":"Yu","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026041423530120700_bib73","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1085\/jgp.201311047","article-title":"Activation of the Ano1 (TMEM16A) chloride channel by calcium is not mediated by calmodulin","volume":"143","author":"Yu","year":"2014","journal-title":"J. Gen. Physiol."},{"key":"2026041423530120700_bib74","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba0310","article-title":"TMEM16F phospholipid scramblase mediates trophoblast fusion and placental development","volume":"6","author":"Zhang","year":"2020","journal-title":"Sci. Adv."},{"key":"2026041423530120700_bib75","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.78840","article-title":"Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion","volume":"11","author":"Zhang","year":"2022","journal-title":"Elife"}],"container-title":["Journal of General Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202313460\/1928784\/jgp_202313460.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202313460\/1928784\/jgp_202313460.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T03:53:09Z","timestamp":1776225189000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/156\/7\/e202313460\/276776\/Niclosamide-potentiates-TMEM16A-and-induces"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,30]]},"references-count":76,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7,1]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.202313460","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.07.31.551400","asserted-by":"object"}]},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,30]]},"article-number":"e202313460"}}