{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:42:11Z","timestamp":1782794531122,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T00:00:00Z","timestamp":1565913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK110167"],"award-info":[{"award-number":["1R01DK110167"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T34GM083688"],"award-info":[{"award-number":["T34GM083688"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>\n                    Fibrosis is an underlying cause of cirrhosis and hepatic failure resulting in end stage liver disease with limited pharmacological options. The beneficial effects of relaxin peptide treatment were demonstrated in clinically relevant animal models of liver fibrosis. However, the use of relaxin is problematic because of a short half\u2010life. The aim of this study was to test the therapeutic effects of recently identified small molecule agonists of the human relaxin receptor, relaxin family peptide receptor 1 (RXFP1). The lead compound of this series, ML290, was selected based on its effects on the expression of fibrosis\u2010related genes in primary human stellate cells. RNA sequencing analysis of TGF\u2010\u03b21\u2013activated LX\u20102 cells showed that ML290 treatment primarily affected extracellular matrix remodeling and cytokine signaling, with expression profiles indicating an antifibrotic effect of ML290. ML290 treatment in human liver organoids with LPS\u2010induced fibrotic phenotype resulted in a significant reduction of type I collagen. The pharmacokinetics of ML290 in mice demonstrated its high stability\n                    <jats:italic>in vivo<\/jats:italic>\n                    , as evidenced by the sustained concentrations of compound in the liver. In mice expressing human\n                    <jats:italic>RXFP1<\/jats:italic>\n                    gene treated with carbon tetrachloride, ML290 significantly reduced collagen content, \u03b1\u2010smooth muscle actin expression, and cell proliferation around portal ducts. In conclusion, ML290 demonstrated antifibrotic effects in liver fibrosis.\u2014Kaftanovskaya, E. M., Ng, H. H., Soula, M., Rivas, B., Myhr, C., Ho, B. A., Cervantes, B. A., Shupe, T. D., Devarasetty, M., Hu, X., Xu, X., Patnaik, S., Wilson, K. J., Barnaeva, E., Ferrer, M., Southall, N. T., Marugan, J. J., Bishop, C. E., Agoulnik, I. U., Agoulnik, A. I. Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis. FASEB J. 33, 12435\u201312446 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201901046r","type":"journal-article","created":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T14:56:20Z","timestamp":1565967380000},"page":"12435-12446","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis"],"prefix":"10.1096","volume":"33","author":[{"given":"Elena M.","family":"Kaftanovskaya","sequence":"first","affiliation":[{"name":"Department of Human and Molecular Genetics Herbert Wertheim College of Medicine, Florida International University Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hooi Hooi","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics Herbert Wertheim College of Medicine, Florida International University Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariluz","family":"Soula","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics Herbert Wertheim College of Medicine, Florida International University Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Rivas","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics Herbert Wertheim College of Medicine, Florida International University Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Myhr","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics Herbert Wertheim College of Medicine, Florida International University Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics Herbert Wertheim College of Medicine, Florida International University Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briana A.","family":"Cervantes","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics Herbert Wertheim College of Medicine, Florida International University Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Shupe","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine Wake Forest School of Medicine Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Devarasetty","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine Wake Forest School of Medicine Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics Herbert Wertheim College of Medicine, Florida International University Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics Herbert Wertheim College of Medicine, Florida International University Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samarjit","family":"Patnaik","sequence":"additional","affiliation":[{"name":"NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Wilson","sequence":"additional","affiliation":[{"name":"NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Barnaeva","sequence":"additional","affiliation":[{"name":"NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Ferrer","sequence":"additional","affiliation":[{"name":"NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel T.","family":"Southall","sequence":"additional","affiliation":[{"name":"NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Marugan","sequence":"additional","affiliation":[{"name":"NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin E.","family":"Bishop","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine Wake Forest School of Medicine Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina U.","family":"Agoulnik","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics Herbert Wertheim College of Medicine, Florida International University Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander I.","family":"Agoulnik","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics Herbert Wertheim College of Medicine, Florida International University Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3823"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28948"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00013.2007"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13529"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.114.009472"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12247"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2009.03.007"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2008.03783.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26627"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374\u2010019\u20100240\u2010y"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.518"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2010.198"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0286"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2008.03780.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0250"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-6543-y"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-74672-2_7"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13695"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13656"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2953"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057112469406"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.06.008"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/js.2017-00112"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.5b01195"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.042127"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075692"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)81686-6"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02916-5"},{"key":"e_1_2_8_30_1","volume-title":"Probe Reports from the NIH Molecular Libraries Program","author":"Xiao J.","year":"2010"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10521-9"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2018.00103"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0200847"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179995"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.114.127209"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2015.00128"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.2144\/000112517"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.12.007"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.589325"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp427"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201901046R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201901046R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201901046R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T20:16:24Z","timestamp":1761682584000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201901046R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,16]]},"references-count":39,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1096\/fj.201901046R"],"URL":"https:\/\/doi.org\/10.1096\/fj.201901046r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,16]]},"assertion":[{"value":"2019-04-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}