{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:13:11Z","timestamp":1789103591755,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DI 1537\/14\u20101"],"award-info":[{"award-number":["DI 1537\/14\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DI 1537\/17\u20101"],"award-info":[{"award-number":["DI 1537\/17\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DI 1537\/20\u20101"],"award-info":[{"award-number":["DI 1537\/20\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DI 1537\/22\u20101"],"award-info":[{"award-number":["DI 1537\/22\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DI 1537\/23\u20101"],"award-info":[{"award-number":["DI 1537\/23\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DI1537\/27\u20101"],"award-info":[{"award-number":["DI1537\/27\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DI1537\/28\u20101"],"award-info":[{"award-number":["DI1537\/28\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK2740(B02)"],"award-info":[{"award-number":["GRK2740(B02)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFBCRC1181(projectC01)"],"award-info":[{"award-number":["SFBCRC1181(projectC01)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFBTR221\/324392634(B04)"],"award-info":[{"award-number":["SFBTR221\/324392634(B04)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFBTR221\/324392634(INF)"],"award-info":[{"award-number":["SFBTR221\/324392634(INF)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100021097","name":"AnaMar","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100021097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030003"],"award-info":[{"award-number":["82030003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Systemic sclerosis (SSc) is a connective tissue disease with fibrotic remodeling of the skin and various internal organs. SSc is associated with the highest case\u2010specific mortality of all rheumatic autoimmune diseases with limited antifibrotic treatment options. Here, we evaluated the therapeutic effects of the highly selective 5\u2010hydroxytryptamine 2B receptor (5\u2010HT<jats:sub>2B<\/jats:sub>R) inhibitor AM1476.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The antifibrotic effects of AM1476 were evaluated in the mouse models of bleomycin\u2010induced pulmonary fibrosis in Tsk\u20101 mice and in mice with sclerodermatous chronic graft\u2010versus\u2010host disease. For further validation, the antifibrotic effects of AM1476 were analyzed in precision cut skin (PCS) slices from patients with SSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AM1476 demonstrated high selectivity for 5\u2010HT<jats:sub>2B<\/jats:sub>R over more than 200 other receptors, including other 5\u2010HT receptors in vitro. AM1476 reduced accumulation of hydroxyproline and fibrotic tissue remodeling of skin and\/or lungs in all three mouse models at well\u2010tolerated doses with a comparable efficacy to that of nintedanib. In PCS of SSc skin, treatment with AM1476 reduced the expression of SSc\u2010specific signature genes. AM1476 demonstrated more pronounced regulation of terms related to fibroblast activation and fibrotic remodeling than mycophenolate mofetil.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We describe AM1476 as a highly selective inhibitor of 5\u2010HT<jats:sub>2B<\/jats:sub>R. Treatment with AM1476 ameliorated fibrosis in three mouse models of SSc and normalized the expression of fibrosis\u2010related genes directly in SSc skin. Because AM1476 also demonstrated good tolerability in a phase 1 trial, further clinical trials with AM1476 are currently in the planning stage.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.43151","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T13:02:50Z","timestamp":1741698170000},"page":"1063-1076","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Antifibrotic effects of specific targeting of the 5\u2010hydroxytryptamine 2B receptor (5\u2010HT<sub>2B<\/sub>R) in murine models and ex vivo models of scleroderma skin"],"prefix":"10.1002","volume":"77","author":[{"given":"Thuong","family":"Trinh\u2010Minh","sequence":"first","affiliation":[{"name":"Department of Rheumatology, University Hospital D\u00fcsseldorf, Heinrich Heine University, D\u00fcsseldorf, Germany; Hiller Research Center University Hospital D\u00fcsseldorf, Heinrich Heine University  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuong","family":"Tran\u2010Manh","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital D\u00fcsseldorf, Heinrich Heine University, D\u00fcsseldorf, Germany; Hiller Research Center University Hospital D\u00fcsseldorf, Heinrich Heine University  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4960-3369","authenticated-orcid":false,"given":"Andrea\u2010Hermina","family":"Gy\u00f6rfi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital D\u00fcsseldorf, Heinrich Heine University, D\u00fcsseldorf, Germany; Hiller Research Center University Hospital D\u00fcsseldorf, Heinrich Heine University  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Dickel","sequence":"additional","affiliation":[{"name":"Chair of Medical Informatics Friedrich\u2010Alexander University of Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Liebel","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital D\u00fcsseldorf, Heinrich Heine University, D\u00fcsseldorf, Germany; Hiller Research Center University Hospital D\u00fcsseldorf, Heinrich Heine University  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital D\u00fcsseldorf, Heinrich Heine University, D\u00fcsseldorf, Germany; Hiller Research Center University Hospital D\u00fcsseldorf, Heinrich Heine University  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2765-0620","authenticated-orcid":false,"given":"Jiucun","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meik","family":"Kunz","sequence":"additional","affiliation":[{"name":"Chair of Medical Informatics Friedrich\u2010Alexander University of Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Arozenius","sequence":"additional","affiliation":[{"name":"AnaMar AB  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Pettersson","sequence":"additional","affiliation":[{"name":"AnaMar AB  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Lindgren","sequence":"additional","affiliation":[{"name":"AnaMar AB  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Wengl\u00e9n","sequence":"additional","affiliation":[{"name":"AnaMar AB  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7408-9333","authenticated-orcid":false,"given":"J\u00f6rg H. W.","family":"Distler","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital D\u00fcsseldorf, Heinrich Heine University, D\u00fcsseldorf, Germany; Hiller Research Center University Hospital D\u00fcsseldorf, Heinrich Heine University  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0322-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07039"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2277"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30933-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101629"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.678457"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230510"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38098"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.07.017"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-403428"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34500"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42033"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0023677213516312"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008720"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI122462"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz5506"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.41.4.467"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201916"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24601-y"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05768-3"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1734"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-022-00218-9"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42781"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.add6570"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI159884"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210294"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202544"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200568"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34424"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-203194"},{"issue":"2","key":"e_1_2_9_32_1","first-page":"S44","article-title":"CCL2, CCL3 and CCL5 chemokines in systemic sclerosis: the correlation with SSc clinical features and the effect of prostaglandin E1 treatment","volume":"30","author":"Bandinelli F","year":"2012","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken401"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200111)44:11<2665::AID-ART446>3.0.CO;2-S"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21497"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21396"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-225158"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2022.155921"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.653950"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02025"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.2741\/3361"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22783"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1586228"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01236-6"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05056-3"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201133"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.43151","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T20:04:04Z","timestamp":1759953844000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.43151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":45,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/art.43151"],"URL":"https:\/\/doi.org\/10.1002\/art.43151","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,17]]},"assertion":[{"value":"2024-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}