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Current diagnostic and prognostic methods lack precision, necessitating biomarkers for personalized treatment strategies. Chitinase 3-like 1 (CHI3L1) has emerged as a potential prognostic marker, with elevated levels correlating with disease severity and relapse risk. Despite its therapeutic potential, few CHI3L1 inhibitors have been identified. Using ligand-based virtual screening and molecular dynamics simulations, Food and Drug Administration-approved drugs have been screened as CHI3L1 inhibitors with the final goals of being repurposed in MS and other inflammatory diseases, offering promising therapeutic approaches. This investigation suggests that sphingosine-1-phosphate receptor modulators such as fingolimod could be potential inhibitors for CHI3L1.<\/jats:p>","DOI":"10.1021\/acsomega.5c01968","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T21:44:33Z","timestamp":1746567873000},"page":"19992-20000","source":"Crossref","is-referenced-by-count":2,"title":["Discovery of Sphingosine-1-Phosphate\nReceptor Modulators\nas Potential CHI3L1 Inhibitors by Ligand-Based Virtual Screening and\nMolecular Dynamics Simulations"],"prefix":"10.1021","volume":"10","author":[{"given":"Elnaz","family":"Aledavood","sequence":"first","affiliation":[{"name":"Centro de Investigaciones Biologicas \u201cMargarita Salas\u201d (CIB-CSIC) , Ramiro de Maeztu 9 , ,","place":["Madrid, Spain, 28040"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3882-6081","authenticated-orcid":true,"given":"Carmen","family":"Gil","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biologicas \u201cMargarita Salas\u201d (CIB-CSIC) , Ramiro de Maeztu 9 , ,","place":["Madrid, Spain, 28040"]},{"name":"Centro de Investigacio\u0301n Biome\u0301dica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III , Melchor Ferna\u0301ndez Almagro 3 , ,","place":["Madrid, Spain, 28029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Comabella","sequence":"additional","affiliation":[{"name":"Servei de Neurologia. Centre d\u2019Esclerosi Mu\u0301ltiple de Catalunya (Cemcat). Institut de Recerca Vall d\u2019Hebron (VHIR) , Passeig de la Vall d\u2019Hebron 129 , ,","place":["Barcelona, Spain, 08035"]},{"name":"Centro de Investigacio\u0301n Biome\u0301dica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III , Melchor Ferna\u0301ndez Almagro 3 , ,","place":["Madrid, Spain, 28029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2707-8110","authenticated-orcid":true,"given":"Ana","family":"Martinez","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biologicas \u201cMargarita Salas\u201d (CIB-CSIC) , Ramiro de Maeztu 9 , ,","place":["Madrid, Spain, 28040"]},{"name":"Centro de Investigacio\u0301n Biome\u0301dica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III , Melchor Ferna\u0301ndez Almagro 3 , ,","place":["Madrid, Spain, 28029"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"issue":"2","key":"2026081811222760000_cit1","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of Multiple Sclerosis:\n2017 Revisions of the McDonald Criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet\nNeurol."},{"issue":"9","key":"2026081811222760000_cit2","doi-asserted-by":"publisher","first-page":"3243","DOI":"10.1007\/s10072-023-06764-2","article-title":"Chitinase-3-like\n1-Protein\nin CSF: A Novel Biomarker for Progression in Patients with Multiple\nSclerosis","volume":"44","author":"Talaat","year":"2023","journal-title":"Neurol. Sci."},{"issue":"3","key":"2026081811222760000_cit3","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029058","article-title":"Biomarkers in Multiple Sclerosis","volume":"9","author":"Paul","year":"2019","journal-title":"Cold Spring Harb. Perspect. Med."},{"issue":"4","key":"2026081811222760000_cit4","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000001164","article-title":"Role of Chitinase\n3-like 1 as a Biomarker in Multiple\nSclerosis: A Systematic Review and Meta-Analysis","volume":"9","author":"Floro","year":"2022","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"1","key":"2026081811222760000_cit5","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000921","article-title":"Chitinases\nand Chitinase-like Proteins\nas Biomarkers in Neurologic Disorders","volume":"8","author":"Pinteac","year":"2021","journal-title":"Neurol.\nNeuroimmunol. Neuroinflamm."},{"key":"2026081811222760000_cit6","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/1742-2094-7-34","article-title":"In Vivo\nCHI3L1 (YKL-40) Expression in Astrocytes in Acute and Chronic Neurological\nDiseases","volume":"7","author":"Bonneh-Barkay","year":"2010","journal-title":"J. Neuroinflammation"},{"key":"2026081811222760000_cit7","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/978-1-59745-447-6_7","article-title":"YKL-40: A Novel\nMarker Shared by Chronic Inflammation\nand Oncogenic Transformation","volume":"511","author":"Roslind","year":"2009","journal-title":"Methods Mol. 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