{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:08:20Z","timestamp":1785409700384,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science and Technology","doi-asserted-by":"crossref","award":["2019R1A6A1A03032869"],"award-info":[{"award-number":["2019R1A6A1A03032869"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2018-NR031048"],"award-info":[{"award-number":["RS-2018-NR031048"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-00523607"],"award-info":[{"award-number":["RS-2025-00523607"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2018-NR031048"],"award-info":[{"award-number":["RS-2018-NR031048"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2025-00523607"],"award-info":[{"award-number":["RS-2025-00523607"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by excessive extracellular matrix (ECM) deposition. Current FDA-approved therapies, such as pirfenidone and nintedanib, offer limited efficacy in halting disease progression. Lysyl oxidase-like 2 (LOXL2) is a key enzyme involved in ECM remodeling and fibrosis. This study investigates Compound #765, a novel indolizine derivative, as a potential LOXL2 inhibitor for IPF treatment. Methods: Compound #765 was synthesized and characterized using spectroscopic methods. Its inhibitory effect on LOXL2 activity was evaluated using LOXL2 enzymatic assays, in vitro fibrosis models with human lung fibroblasts, and in vivo models of pulmonary fibrosis, including bleomycin-treated and TGF-\u03b21-overexpressing transgenic mice. In silico docking studies predicted the binding affinity of Compound #765 to LOXL2. Results: Compound #765 targeted LOXL2 activity and reduced collagen production in lung fibroblasts. In both bleomycin-induced pulmonary fibrosis and TGF-\u03b21-overexpressing murine models, Compound #765 significantly alleviated fibrosis, as indicated by reduced collagen accumulation and inflammatory cell infiltration. The in silico docking studies predicted favorable binding affinity to LOXL2, which was confirmed through in vitro experiments. Importantly, Compound #765 suppressed fibrosis-associated markers in fibroblasts derived from IPF patients, suggesting translational potential. Conclusions: These results demonstrate that Compound #765 functions as a LOXL2 inhibitor with significant anti-fibrotic effects in vitro and in vivo, offering a promising therapeutic approach for IPF and other fibrotic lung diseases.<\/jats:p>","DOI":"10.3390\/pharmaceutics18050554","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:32:21Z","timestamp":1777555941000},"page":"554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Lysyl Oxidase-like 2: A Therapeutic Strategy for Idiopathic Pulmonary Fibrosis with a Novel Indolizine Derivative"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6696-7199","authenticated-orcid":false,"given":"Doo Hee","family":"Shim","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5634-9709","authenticated-orcid":false,"given":"Min Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si 16995, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7679-794X","authenticated-orcid":false,"given":"Hyeon Woo","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-0688","authenticated-orcid":false,"given":"Mi Na","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Institute of Allergy, Severance Hospital, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung Hyun","family":"Sohn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Institute of Allergy, Severance Hospital, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunhee","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0849-5517","authenticated-orcid":false,"given":"Ikyon","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9514-3658","authenticated-orcid":false,"given":"Chun Geun","family":"Lee","sequence":"additional","affiliation":[{"name":"Intercollege, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3124-8557","authenticated-orcid":false,"given":"Jack A.","family":"Elias","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeon Han","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5273-3113","authenticated-orcid":false,"given":"Jae Myun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41586-020-2938-9","article-title":"Fibrosis: From mechanisms to medicines","volume":"587","author":"Henderson","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/nm.2807","article-title":"Mechanisms of fibrosis: Therapeutic translation for fibrotic disease","volume":"18","author":"Wynn","year":"2012","journal-title":"Nat. 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