{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T20:21:29Z","timestamp":1776284489026,"version":"3.50.1"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSTC 112-2320-B-400-012"],"award-info":[{"award-number":["NSTC 112-2320-B-400-012"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["109-2320-B-400-011-MY3"],"award-info":[{"award-number":["109-2320-B-400-011-MY3"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["111-2811-B-400-018"],"award-info":[{"award-number":["111-2811-B-400-018"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["109-2811-B-400-518"],"award-info":[{"award-number":["109-2811-B-400-518"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["110-2811-B-400-522"],"award-info":[{"award-number":["110-2811-B-400-522"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.ejmech.2025.117985","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T06:30:49Z","timestamp":1752906649000},"page":"117985","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Synthesis and evaluation of a novel class of spiro[chromene-2,2\u2032-indoline] derivatives as potent inhibitors of peptidylarginine deiminase IV to treat rheumatoid arthritis"],"prefix":"10.1016","volume":"298","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3994-475X","authenticated-orcid":false,"given":"Cheng-Wei","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8640-9525","authenticated-orcid":false,"given":"Yue-Zhi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8954-0263","authenticated-orcid":false,"given":"Hsing-Yu","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4012-0149","authenticated-orcid":false,"given":"Shiow-Ju","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2025.117985_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.clim.2022.109134","article-title":"Citrullination: a modification important in the pathogenesis of autoimmune diseases","volume":"245","author":"Zhu","year":"2022","journal-title":"Clin. Immunol."},{"issue":"2","key":"10.1016\/j.ejmech.2025.117985_bib2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/bip.22127","article-title":"The protein arginine deiminases: structure, function, inhibition, and disease","volume":"99","author":"Bicker","year":"2013","journal-title":"Biopolymers"},{"issue":"9","key":"10.1016\/j.ejmech.2025.117985_bib3","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.tcb.2022.01.014","article-title":"Insights into peptidylarginine deiminase expression and citrullination pathways","volume":"32","author":"Yu","year":"2022","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.ejmech.2025.117985_bib4","series-title":"Ever-Expanding Connections Between Peptidylarginine Deiminase 4 and Rheumatoid Arthritis","author":"Shelef","year":"2025"},{"key":"10.1016\/j.ejmech.2025.117985_bib5","doi-asserted-by":"crossref","DOI":"10.1002\/art.43168","article-title":"Anti-peptidylarginine deiminase 4 autoantibodies derived from patients with rheumatoid arthritis exert pathogenic effects by activating monocytes and exacerbating inflammatory arthritis","author":"Won","year":"2025","journal-title":"Arthritis Rheumatol."},{"key":"10.1016\/j.ejmech.2025.117985_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2025.119337","article-title":"Glycyrrhizic acid reduces neutrophil extracellular trap formation to ameliorate colitis-associated colorectal cancer by inhibiting peptidylarginine deiminase 4","volume":"341","author":"Chen","year":"2025","journal-title":"J. Ethnopharmacol."},{"issue":"1","key":"10.1016\/j.ejmech.2025.117985_bib7","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1038\/s41598-023-30246-2","article-title":"Alleviation of arthritis through prevention of neutrophil extracellular traps by an orally available inhibitor of protein arginine deiminase 4","volume":"13","author":"Gajendran","year":"2023","journal-title":"Sci. Rep."},{"issue":"3","key":"10.1016\/j.ejmech.2025.117985_bib8","doi-asserted-by":"crossref","first-page":"256","DOI":"10.2174\/1871520622666220614115309","article-title":"The role of peptidyl arginine deiminase IV(PADI4) in cancers","volume":"23","author":"Wu","year":"2023","journal-title":"Anti Cancer Agents Med. Chem."},{"issue":"4","key":"10.1016\/j.ejmech.2025.117985_bib9","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1021\/jm301755q","article-title":"Novel inhibitors of protein arginine deiminase with potential activity in multiple sclerosis animal model","volume":"56","author":"Wei","year":"2013","journal-title":"J. Med. Chem."},{"issue":"19","key":"10.1016\/j.ejmech.2025.117985_bib10","doi-asserted-by":"crossref","first-page":"6919","DOI":"10.1021\/jm2008985","volume":"54","author":"Causey","year":"2011","journal-title":"J. Med. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2025.117985_bib11","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1021\/jm501636x","article-title":"Design, synthesis, and biological evaluation of tetrazole analogs of Cl-amidine as protein arginine deiminase inhibitors","volume":"58","author":"Subramanian","year":"2015","journal-title":"J. Med. Chem."},{"issue":"7","key":"10.1016\/j.ejmech.2025.117985_bib12","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1021\/acs.jmedchem.7b00274","article-title":"Development of a selective inhibitor of protein arginine deiminase 2","volume":"60","author":"Muth","year":"2017","journal-title":"J. Med. Chem."},{"issue":"1","key":"10.1016\/j.ejmech.2025.117985_bib13","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1021\/cb200258q","article-title":"Synthesis and screening of a haloacetamidine containing library to identify PAD4 selective inhibitors","volume":"7","author":"Jones","year":"2012","journal-title":"ACS Chem. Biol."},{"issue":"10","key":"10.1016\/j.ejmech.2025.117985_bib14","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1021\/acsmedchemlett.2c00387","article-title":"Novel peptidylarginine deiminase type 4 (PAD4) inhibitors","volume":"13","author":"Sabnis","year":"2022","journal-title":"ACS Med. Chem. Lett."},{"issue":"1","key":"10.1016\/j.ejmech.2025.117985_bib15","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1021\/acsmedchemlett.1c00689","article-title":"Novel macrocyclic peptidylarginine deiminase type 4 (PAD4) inhibitors","volume":"13","author":"Sabnis","year":"2022","journal-title":"ACS Med. Chem. Lett."},{"issue":"10","key":"10.1016\/j.ejmech.2025.117985_bib16","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1021\/acsmedchemlett.8b00283","article-title":"Synthesis and biological evaluation of an indazole-based selective protein arginine deiminase 4 (PAD4) inhibitor","volume":"9","author":"Tjin","year":"2018","journal-title":"ACS Med. Chem. Lett."},{"issue":"9","key":"10.1016\/j.ejmech.2025.117985_bib17","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1021\/acsmedchemlett.6b00215","article-title":"Cellular activity of new small molecule protein arginine deiminase 3 (PAD3) inhibitors","volume":"7","author":"Jamali","year":"2016","journal-title":"ACS Med. Chem. Lett."},{"issue":"12","key":"10.1016\/j.ejmech.2025.117985_bib18","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1021\/ml300288d","article-title":"D-amino acid based protein arginine deiminase inhibitors: synthesis, pharmacokinetics, and in cellulo efficacy","volume":"3","author":"Bicker","year":"2012","journal-title":"ACS Med. Chem. Lett."},{"issue":"9","key":"10.1016\/j.ejmech.2025.117985_bib19","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20092174","article-title":"Discovery of novel potential reversible peptidyl arginine deiminase inhibitor","volume":"20","author":"Aliko","year":"2019","journal-title":"Int. J. Mol. Sci."},{"issue":"3","key":"10.1016\/j.ejmech.2025.117985_bib20","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nchembio.1735","article-title":"Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation","volume":"11","author":"Lewis","year":"2015","journal-title":"Nat. Chem. Biol."},{"issue":"6","key":"10.1016\/j.ejmech.2025.117985_bib21","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1080\/13543776.2025.2484366","article-title":"A patent review of peptidylarginine deiminase 4 (PAD4) inhibitors (2014-present)","volume":"35","author":"Aiken","year":"2025","journal-title":"Expert Opin. Ther. Pat."},{"issue":"12","key":"10.1016\/j.ejmech.2025.117985_bib22","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1136\/annrheumdis-2014-205365","article-title":"Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL\/lpr mice","volume":"74","author":"Knight","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.ejmech.2025.117985_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbrc.2024.149668","article-title":"Vitamin B12 inhibits peptidylarginine deiminases and ameliorates rheumatoid arthritis in CAIA mice","volume":"704","author":"Yang","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"11","key":"10.1016\/j.ejmech.2025.117985_bib24","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1111\/bph.12619","article-title":"Anti-arthritis effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal are mediated by inhibition of the STAT3 pathway","volume":"171","author":"Ban","year":"2014","journal-title":"Br. J. Pharmacol."},{"issue":"6","key":"10.1016\/j.ejmech.2025.117985_bib25","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.chembiol.2018.03.002","article-title":"The rheumatoid arthritis-associated citrullinome","volume":"25","author":"Tilvawala","year":"2018","journal-title":"Cell Chem. Biol."},{"issue":"1","key":"10.1016\/j.ejmech.2025.117985_bib26","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1097\/BOR.0000000000000452","article-title":"Rheumatoid arthritis and citrullination","volume":"30","author":"Darrah","year":"2018","journal-title":"Curr. Opin. Rheumatol."},{"issue":"12","key":"10.1016\/j.ejmech.2025.117985_bib27","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20123093","article-title":"Reduced anti-histone antibodies and increased risk of rheumatoid arthritis associated with a single nucleotide polymorphism in PADI4 in North Americans","volume":"20","author":"Mergaert","year":"2019","journal-title":"Int. J. Mol. Sci."},{"issue":"2","key":"10.1016\/j.ejmech.2025.117985_bib28","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/03009742.2019.1641216","article-title":"Peptidylarginine deiminase 4 (PAD4) activity in early rheumatoid arthritis","volume":"49","author":"Jonsson","year":"2020","journal-title":"Scand. J. Rheumatol."},{"key":"10.1016\/j.ejmech.2025.117985_bib29","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.ejmech.2016.09.003","article-title":"Discovery, structure-activity relationship studies, and anti-nociceptive effects of N-(1,2,3,4-tetrahydro-1-isoquinolinylmethyl)benzamides as novel opioid receptor agonists","volume":"126","author":"Chen","year":"2017","journal-title":"Eur. J. Med. Chem."},{"issue":"11","key":"10.1016\/j.ejmech.2025.117985_bib30","first-page":"1128","article-title":"Thermo- and photochromic dyes: spiro(indolinebenzopyrans). 2\u2014detailed assignment of the 1H NMR spectra and structural aspects of the closed form of 1","volume":"30","author":"Keum","year":"1992","journal-title":"3,3-trimethylspiro(indoline-2,2\u2032-benzopyrans)"},{"issue":"19","key":"10.1016\/j.ejmech.2025.117985_bib31","doi-asserted-by":"crossref","first-page":"8744","DOI":"10.1021\/acs.joc.6b01193","article-title":"Comparative evaluation of substituent effect on the photochromic properties of spiropyrans and spirooxazines","volume":"81","author":"Balmond","year":"2016","journal-title":"J. Org. Chem."},{"issue":"4","key":"10.1016\/j.ejmech.2025.117985_bib32","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S1005-9040(06)60151-7","article-title":"Spectral properties and photochromic characteristics of spiropyran Dyes1 1Supported by the scientific research foundation for the returned overseas Chinese scholars, Ministry of Education(No. SRF-2004-527)","volume":"22","author":"Shen","year":"2006","journal-title":"Chem. Res. Chin. Univ."},{"issue":"1","key":"10.1016\/j.ejmech.2025.117985_bib33","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1186\/1471-2407-12-500","article-title":"Identification of PADI2 as a potential breast cancer biomarker and therapeutic target","volume":"12","author":"McElwee","year":"2012","journal-title":"BMC Cancer"},{"key":"10.1016\/j.ejmech.2025.117985_bib34","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fmed.2020.00078","article-title":"Uremic vascular calcification is correlated with oxidative elastic lamina injury, contractile smooth muscle cell loss, osteogenesis, and apoptosis: the human pathobiological evidence","volume":"7","author":"Chang","year":"2020","journal-title":"Front. Med."},{"key":"10.1016\/j.ejmech.2025.117985_bib35","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.jconrel.2022.10.002","article-title":"Glycosylation of OVA antigen-loaded PLGA nanoparticles enhances DC-targeting for cancer vaccination","volume":"351","author":"Chou","year":"2022","journal-title":"J. Contr. Release: Offic. J. Control. Release Soc."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425007500?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425007500?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T02:22:24Z","timestamp":1772763744000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523425007500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":35,"alternative-id":["S0223523425007500"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.117985","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synthesis and evaluation of a novel class of spiro[chromene-2,2\u2032-indoline] derivatives as potent inhibitors of peptidylarginine deiminase IV to treat rheumatoid arthritis","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.117985","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"117985"}}