{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:52:13Z","timestamp":1790211133317,"version":"4.1.0"},"reference-count":30,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2023,10]]},"DOI":"10.1016\/j.ejmech.2023.115583","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T02:10:31Z","timestamp":1687227031000},"page":"115583","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"special_numbering":"C","title":["Discovery of tetrasubstituted thiophenes as Cisd2 activators: A potential novel therapeutic option in nonalcoholic fatty liver disease"],"prefix":"10.1016","volume":"258","author":[{"given":"Chun-Hsu","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Qing","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yesudoss Christu","family":"Rajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Wen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Yu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen-Shin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Yi","family":"Shiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Yu","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Shiou","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Hui","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng-Kuang","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Fen","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2828-028X","authenticated-orcid":false,"given":"Jinq-Chyi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2023.115583_bib1","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.cell.2021.04.015","article-title":"Mechanisms and disease consequences of nonalcoholic fatty liver disease","volume":"184","author":"Loomba","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2023.115583_bib2","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"10.1016\/j.ejmech.2023.115583_bib3","doi-asserted-by":"crossref","first-page":"s86","DOI":"10.3350\/cmh.2022.0442","article-title":"Nonalcoholic fatty liver disease and non-liver comorbidities","volume":"29","author":"Manikat","year":"2023","journal-title":"Clin. Mol. Hepatol."},{"key":"10.1016\/j.ejmech.2023.115583_bib4","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.abc6165","article-title":"Uniting the divergent Wolfram syndrome-linked proteins WFS1 and CISD2 as modulators of Ca2+ signaling","volume":"14","author":"Loncke","year":"2021","journal-title":"Sci. Signal."},{"key":"10.1016\/j.ejmech.2023.115583_bib5","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1101\/gad.1779509","article-title":"Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice","volume":"23","author":"Chen","year":"2009","journal-title":"Genes Dev."},{"key":"10.1016\/j.ejmech.2023.115583_bib6","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.4161\/auto.5.7.9351","article-title":"Cisd2 mediates mitochondrial integrity and life span in mammals","volume":"5","author":"Chen","year":"2009","journal-title":"Autophagy"},{"key":"10.1016\/j.ejmech.2023.115583_bib7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000508","article-title":"Cisd2 is essential to delaying cardiac aging and to maintaining heart functions","volume":"17","author":"Yeh","year":"2019","journal-title":"PLoS Biol."},{"key":"10.1016\/j.ejmech.2023.115583_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbamcr.2021.118954","article-title":"CISD2 maintains cellular homeostasis","volume":"1868","author":"Shen","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"10.1016\/j.ejmech.2023.115583_bib9","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13523","article-title":"Cisd2 slows down liver aging and attenuates age-related metabolic dysfunction in male mice","volume":"20","author":"Huang","year":"2021","journal-title":"Aging Cell"},{"key":"10.1016\/j.ejmech.2023.115583_bib10","doi-asserted-by":"crossref","first-page":"3956","DOI":"10.1093\/hmg\/dds210","article-title":"A persistent level of Cisd2 extends healthy lifespan and delays aging in mice","volume":"21","author":"Wu","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ejmech.2023.115583_bib11","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.3109\/10715762.2014.936431","article-title":"Cisd2 mediates lifespan: is there an interconnection among Ca2+ homeostasis, autophagy, and lifespan?","volume":"48","author":"Wang","year":"2014","journal-title":"Free Radic. Res."},{"key":"10.1016\/j.ejmech.2023.115583_bib12","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1016\/j.celrep.2017.10.099","article-title":"CISD2 haploinsufficiency disrupts calcium homeostasis, causes nonalcoholic fatty liver disease, and promotes hepatocellular carcinoma","volume":"21","author":"Shen","year":"2017","journal-title":"Cell Rep."},{"key":"10.1016\/j.ejmech.2023.115583_bib13","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.tem.2019.02.005","article-title":"Calcium signaling as a therapeutic target for liver steatosis","volume":"30","author":"Ali","year":"2019","journal-title":"Trends Endocrinol. Metabol."},{"key":"10.1016\/j.ejmech.2023.115583_bib14","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3390\/antiox10040559","article-title":"Cisd2 protects the liver from oxidative stress and ameliorates western diet-induced nonalcoholic fatty liver disease","volume":"10","author":"Huang","year":"2021","journal-title":"Antioxidants"},{"key":"10.1016\/j.ejmech.2023.115583_bib15","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1021\/jf0000528","article-title":"In vitro availability of flavonoids and other phenolics in orange juice","volume":"49","author":"Gil-Izquierdo","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.ejmech.2023.115583_bib16","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12929-022-00838-7","article-title":"Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice","volume":"29","author":"Yeh","year":"2022","journal-title":"J. Biomed. Sci."},{"key":"10.1016\/j.ejmech.2023.115583_bib17","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/cmdc.201200464","article-title":"3D-QSAR-assisted drug design: identification of a potent quinazoline-based aurora kinase inhibitor","volume":"8","author":"Ke","year":"2013","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2023.115583_bib18","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1002\/cber.19650981120","article-title":"Heterocyclen aus CH-aciden nitrilen, VII. 2-amino-thiophene aus \u03b1-oxo-mercaptanen und methylenaktiven nitrilen","volume":"98","author":"Gewald","year":"1965","journal-title":"Chem. Ber."},{"key":"10.1016\/j.ejmech.2023.115583_bib19","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/jhet.5570360203","article-title":"2-Aminothiophenes by the Gewald reaction","volume":"36","author":"Sabnis","year":"1999","journal-title":"J. Heterocycl. Chem."},{"key":"10.1016\/j.ejmech.2023.115583_bib20","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3998\/ark.5550190.0011.105","article-title":"Gewald reaction: synthesis, properties and applications of substituted 2-aminothiophenes","volume":"I","author":"Puterov\u00e1","year":"2010","journal-title":"ARKIVOC (Gainesville, FL, U. S.)"},{"key":"10.1016\/j.ejmech.2023.115583_bib21","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11030-010-9229-6","article-title":"The Gewald multicomponent reaction","volume":"15","author":"Huang","year":"2011","journal-title":"Mol. Divers."},{"key":"10.1016\/j.ejmech.2023.115583_bib22","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1021\/jm501437v","article-title":"Design, synthesis, and biological evaluation of sulfonyl acrylonitriles as novel inhibitors of cancer metastasis and spread","volume":"58","author":"Shen","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115583_bib23","doi-asserted-by":"crossref","first-page":"12511","DOI":"10.1021\/acs.jmedchem.0c00579","article-title":"Discovery of an orally available diazabicyclooctane inhibitor (ETX0282) of class A, C, and D serine \u03b2-lactamases","volume":"63","author":"Durand-R\u00e9ville","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115583_bib24","series-title":"Novel Compounds and Compositions as Protease Inhibitors","author":"Buysse","year":"2000"},{"key":"10.1016\/j.ejmech.2023.115583_bib25","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1055\/s-0035-1561459","article-title":"Synthesis of novel 3-acetyl-2-aminothiophenes and investigation of their behaviour in the reaction with Vilsmeier\u2013Haack reagent","volume":"48","author":"Abdelwahab","year":"2016","journal-title":"Synthesis"},{"key":"10.1016\/j.ejmech.2023.115583_bib26","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/S0040-4020(03)00054-1","article-title":"Preparation of thieno[2,3-b]pyrroles starting from ketene-N,S-acetals","volume":"59","author":"Sommen","year":"2003","journal-title":"Tetrahedron"},{"key":"10.1016\/j.ejmech.2023.115583_bib27","doi-asserted-by":"crossref","first-page":"5129","DOI":"10.1021\/jm901902w","article-title":"Synthesis, inhibitory activity of cholinesterases, and neuroprotective profile of novel 1,8-naphthyridine derivatives","volume":"53","author":"de Los R\u00edos","year":"2010","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115583_bib28","doi-asserted-by":"crossref","first-page":"515","DOI":"10.2165\/00003088-200342060-00002","article-title":"Metabolic stability for drug discovery and development: pharmacokinetic and biochemical challenges","volume":"42","author":"Masimirembwa","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"10.1016\/j.ejmech.2023.115583_bib29","doi-asserted-by":"crossref","first-page":"345","DOI":"10.2478\/acph-2019-0024","article-title":"Metabolic stability and its role in the discovery of new chemical entities","volume":"69","author":"S\u0142oczy\u0144ska","year":"2019","journal-title":"Acta Pharm."},{"key":"10.1016\/j.ejmech.2023.115583_bib30","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.3390\/biomedicines9091229","article-title":"Cisd2 preserves the youthful pattern of the liver proteome during natural aging of mice","volume":"9","author":"Huang","year":"2021","journal-title":"Biomedicines"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423005494?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423005494?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:58:38Z","timestamp":1759330718000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523423005494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10]]},"references-count":30,"alternative-id":["S0223523423005494"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115583","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2023,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of tetrasubstituted thiophenes as Cisd2 activators: A potential novel therapeutic option in nonalcoholic fatty liver disease","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115583","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"115583"}}