{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T01:25:52Z","timestamp":1778894752075,"version":"3.51.4"},"reference-count":34,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["molpharm.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Pharmacology"],"published-print":{"date-parts":[[2022,4]]},"DOI":"10.1124\/molpharm.121.000421","type":"journal-article","created":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T17:40:12Z","timestamp":1644169212000},"page":"236-245","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"title":["A High-Throughput Screening Assay to Identify Drugs that Can Treat Long QT Syndrome Caused by Trafficking-Deficient KV11.1 (hERG) Variants"],"prefix":"10.1016","volume":"101","author":[{"given":"Christian L.","family":"Egly","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Blackwell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Schmeckpeper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian P.","family":"Delisle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. David","family":"Weaver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn C.","family":"Knollmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1124\/molpharm.121.000421_bib1","doi-asserted-by":"crossref","first-page":"C693","DOI":"10.1152\/ajpcell.00383.2014","article-title":"Protein kinase A stimulates Kv7.1 surface expression by regulating Nedd4-2-dependent endocytic trafficking","volume":"309","author":"Andersen","year":"2015","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1124\/molpharm.121.000421_bib2","doi-asserted-by":"crossref","first-page":"36841","DOI":"10.1074\/jbc.M113.525931","article-title":"A phosphoinositide 3-kinase (PI3K)-serum- and glucocorticoid-inducible kinase 1 (SGK1) pathway promotes Kv7.1 channel surface expression by inhibiting Nedd4-2 protein","volume":"288","author":"Andersen","year":"2013","journal-title":"J Biol Chem"},{"key":"10.1124\/molpharm.121.000421_bib3","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1161\/CIRCULATIONAHA.105.570200","article-title":"Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism","volume":"113","author":"Anderson","year":"2006","journal-title":"Circulation"},{"key":"10.1124\/molpharm.121.000421_bib4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms6535","article-title":"Large-scale mutational analysis of Kv11.1 reveals molecular insights into type 2 long QT syndrome","volume":"5","author":"Anderson","year":"2014","journal-title":"Nat Commun"},{"key":"10.1124\/molpharm.121.000421_bib5","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1124\/mol.110.066928","article-title":"Development of a selective small-molecule inhibitor of Kir1.1, the renal outer medullary potassium channel","volume":"79","author":"Bhave","year":"2011","journal-title":"Mol Pharmacol"},{"key":"10.1124\/molpharm.121.000421_bib6","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.eplepsyres.2004.10.002","article-title":"Effects of the antiepileptic drugs lamotrigine, topiramate and gabapentin on hERG potassium currents","volume":"63","author":"Danielsson","year":"2005","journal-title":"Epilepsy Res"},{"key":"10.1124\/molpharm.121.000421_bib7","doi-asserted-by":"crossref","first-page":"4989","DOI":"10.1074\/jbc.M107345200","article-title":"The binding site for channel blockers that rescue misprocessed human long QT syndrome type 2 ether-a-gogo-related gene (HERG) mutations","volume":"277","author":"Ficker","year":"2002","journal-title":"J Biol Chem"},{"key":"10.1124\/molpharm.121.000421_bib8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yjmcc.2020.04.027","article-title":"A distinct molecular mechanism by which phenytoin rescues a novel long QT 3 variant","volume":"144","author":"Gando","year":"2020","journal-title":"J Mol Cell Cardiol"},{"key":"10.1124\/molpharm.121.000421_bib9","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3001862","article-title":"The NCGC pharmaceutical collection: a comprehensive resource of clinically approved drugs enabling repurposing and chemical genomics","volume":"3","author":"Huang","year":"2011","journal-title":"Sci Transl Med"},{"key":"10.1124\/molpharm.121.000421_bib10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-06514-5","article-title":"Identification of small-molecule ion channel modulators in C. elegans channelopathy models","volume":"9","author":"Jiang","year":"2018","journal-title":"Nat Commun"},{"key":"10.1124\/molpharm.121.000421_bib11","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.hrthm.2009.05.021","article-title":"Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test","volume":"6","author":"Kapplinger","year":"2009","journal-title":"Heart Rhythm"},{"key":"10.1124\/molpharm.121.000421_bib12","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1124\/mol.109.059840","article-title":"High-throughput screening reveals a small-molecule inhibitor of the renal outer medullary potassium channel and Kir7.1","volume":"76","author":"Lewis","year":"2009","journal-title":"Mol Pharmacol"},{"key":"10.1124\/molpharm.121.000421_bib13","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.yjmcc.2018.01.009","article-title":"Restoration of mutant hERG stability by inhibition of HDAC6","volume":"115","author":"Li","year":"2018","journal-title":"J Mol Cell Cardiol"},{"key":"10.1124\/molpharm.121.000421_bib14","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ab.2011.06.040","article-title":"Identification of novel KCNQ4 openers by a high-throughput fluorescence-based thallium flux assay","volume":"418","author":"Li","year":"2011","journal-title":"Anal Biochem"},{"key":"10.1124\/molpharm.121.000421_bib15","article-title":"High-throughput electrophysiological assays for voltage gated ion channels using SyncroPatch 768PE","volume":"12","author":"Li","year":"2017","journal-title":"PLoS One"},{"key":"10.1124\/molpharm.121.000421_bib16","doi-asserted-by":"crossref","first-page":"21971","DOI":"10.1074\/jbc.M116.749366","article-title":"Pharmacological Correction of Trafficking Defects in ATP-sensitive Potassium Channels Caused by Sulfonylurea Receptor 1 Mutations","volume":"291","author":"Martin","year":"2016","journal-title":"J Biol Chem"},{"key":"10.1124\/molpharm.121.000421_bib17","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1093\/eurheartj\/ehx394","article-title":"Identification of a targeted and testable antiarrhythmic therapy for long-QT syndrome type 2 using a patient-specific cellular model","volume":"39","author":"Mehta","year":"2018","journal-title":"Eur Heart J"},{"key":"10.1124\/molpharm.121.000421_bib18","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1161\/CIRCGEN.120.002950","article-title":"Promise and Potential Peril With Lumacaftor for the Trafficking Defective Type 2 Long-QT Syndrome-Causative Variants, p.G604S, p.N633S, and p.R685P, Using Patient-Specific Re-Engineered Cardiomyocytes","volume":"13","author":"O\u2019Hare","year":"2020","journal-title":"Circ Genom Precis Med"},{"key":"10.1124\/molpharm.121.000421_bib19","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s10038-003-0109-0","article-title":"3\u2032 rapid amplification of cDNA ends (RACE) walking for rapid structural analysis of large transcripts","volume":"49","author":"Ozawa","year":"2004","journal-title":"J Hum Genet"},{"key":"10.1124\/molpharm.121.000421_bib20","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.yjmcc.2019.03.016","article-title":"Fluvastatin inhibits Rab5-mediated IKs internalization caused by chronic Ca2+-dependent PKC activation","volume":"129","author":"Parks","year":"2019","journal-title":"J Mol Cell Cardiol"},{"key":"10.1124\/molpharm.121.000421_bib21","doi-asserted-by":"crossref","first-page":"4031","DOI":"10.1113\/JP271805","article-title":"Rescue of protein expression defects may not be enough to abolish the pro-arrhythmic phenotype of long QT type 2 mutations","volume":"594","author":"Perry","year":"2016","journal-title":"J Physiol"},{"key":"10.1124\/molpharm.121.000421_bib22","doi-asserted-by":"crossref","first-page":"39613","DOI":"10.1074\/jbc.M112.380162","article-title":"Identification and characterization of a compound that protects cardiac tissue from human Ether-\u00e0-go-go-related gene (hERG)-related drug-induced arrhythmias","volume":"287","author":"Potet","year":"2012","journal-title":"J Biol Chem"},{"key":"10.1124\/molpharm.121.000421_bib23","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1056\/NEJMoa022147","article-title":"Risk stratification in the long-QT syndrome","volume":"348","author":"Priori","year":"2003","journal-title":"N Engl J Med"},{"key":"10.1124\/molpharm.121.000421_bib24","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.hrthm.2016.01.012","article-title":"hERG 1a LQT2 C-terminus truncation mutants display hERG 1b-dependent dominant negative mechanisms","volume":"13","author":"Puckerin","year":"2016","journal-title":"Heart Rhythm"},{"key":"10.1124\/molpharm.121.000421_bib25","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1161\/01.CIR.0000019513.50928.74","article-title":"Pharmacological rescue of human K(+) channel long-QT2 mutations: human ether-a-go-go-related gene rescue without block","volume":"105","author":"Rajamani","year":"2002","journal-title":"Circulation"},{"key":"10.1124\/molpharm.121.000421_bib26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2011.00075","article-title":"Discovery, characterization, and structure-activity relationships of an inhibitor of inward rectifier potassium (Kir) channels with preference for Kir2.3, Kir3.x, and Kir7.1","volume":"2","author":"Raphemot","year":"2011","journal-title":"Front Pharmacol"},{"key":"10.1124\/molpharm.121.000421_bib27","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1093\/eurheartj\/eht089","article-title":"The long QT syndrome: a transatlantic clinical approach to diagnosis and therapy","volume":"34","author":"Schwartz","year":"2013","journal-title":"Eur Heart J"},{"key":"10.1124\/molpharm.121.000421_bib28","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1093\/eurheartj\/ehz023","article-title":"From patient-specific induced pluripotent stem cells to clinical translation in long QT syndrome Type 2","volume":"40","author":"Schwartz","year":"2019","journal-title":"Eur Heart J"},{"key":"10.1124\/molpharm.121.000421_bib29","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1161\/CIRCULATIONAHA.109.863209","article-title":"Prevalence of the congenital long-QT syndrome","volume":"120","author":"Schwartz","year":"2009","journal-title":"Circulation"},{"key":"10.1124\/molpharm.121.000421_bib30","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1177\/1087057104268749","article-title":"A thallium-sensitive, fluorescence-based assay for detecting and characterizing potassium channel modulators in mammalian cells","volume":"9","author":"Weaver","year":"2004","journal-title":"J Biomol Screen"},{"key":"10.1124\/molpharm.121.000421_bib31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/108705719900400206","article-title":"A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays","volume":"4","author":"Zhang","year":"1999","journal-title":"J Biomol Screen"},{"key":"10.1124\/molpharm.121.000421_bib32","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1113\/jphysiol.2003.039198","article-title":"Modulation of human ether-\u00e0-go-go-related K+ (HERG) channel inactivation by Cs+ and K+","volume":"548","author":"Zhang","year":"2003","journal-title":"J Physiol"},{"key":"10.1124\/molpharm.121.000421_bib33","doi-asserted-by":"crossref","first-page":"31123","DOI":"10.1074\/jbc.274.44.31123","article-title":"Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome. Pharmacological and temperature effects","volume":"274","author":"Zhou","year":"1999","journal-title":"J Biol Chem"},{"key":"10.1124\/molpharm.121.000421_bib34","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1089\/adt.2010.0339","article-title":"Profiling diverse compounds by flux- and electrophysiology-based primary screens for inhibition of human Ether-\u00e0-go-go related gene potassium channels","volume":"8","author":"Zou","year":"2010","journal-title":"Assay Drug Dev Technol"}],"container-title":["Molecular Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24012197?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24012197?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/molpharm.121.000421","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T08:49:20Z","timestamp":1739954960000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0026895X24012197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["S0026895X24012197"],"URL":"https:\/\/doi.org\/10.1124\/molpharm.121.000421","relation":{},"ISSN":["0026-895X"],"issn-type":[{"value":"0026-895X","type":"print"}],"subject":[],"published":{"date-parts":[[2022,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A High-Throughput Screening Assay to Identify Drugs that Can Treat Long QT Syndrome Caused by Trafficking-Deficient KV11.1 (hERG) Variants","name":"articletitle","label":"Article Title"},{"value":"Molecular Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/molpharm.121.000421","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}