{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:00:37Z","timestamp":1790301637909,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>SB216763 has demonstrated efficacy in treating pulmonary fibrosis in animal models, but its underlying mechanisms remain poorly understood. This study used network pharmacology, molecular docking, and molecular dynamics simulations to explore the molecular mechanisms by which SB216763 exerts therapeutic effects on pulmonary fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The targets of SB216763 were screened using the PharmMapper database, while pulmonary fibrosis\u2010related targets were obtained from GeneCards and OMIM databases. A Venn diagram generated from these datasets highlighted overlapping targets. Protein\u2013protein interaction networks were constructed using the STRING database and Cytoscape software to assess target importance. GO and KEGG enrichment analyses using the Metascape database revealed relevant biological functions and signaling pathways of SB216763 in the treatment of pulmonary fibrosis. Molecular docking investigated the binding affinity and binding mode of SB216763 with GSK\u20103\u03b2. Molecular dynamics simulations further confirmed the stability of the complex formed by SB216763 and GSK\u20103\u03b2. Finally, Western blotting, Griess assays, and ELISA were employed to validate the effect of SB216763 on macrophage functional plasticity in pulmonary fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Network pharmacology analysis identified the following three key targets of SB216763 in pulmonary fibrosis: AKT1, GSK3B, and TGFBR1, along with the PI3K\u2010AKT signaling pathway. Molecular docking and dynamics simulations revealed that SB216763 primarily interacts with GSK\u20103\u03b2 through hydrogen bonds and hydrophobic interactions. In\u00a0vitro validation demonstrated significant anti\u2010inflammatory and antifibrotic effects of SB216763. Additionally, SB216763 exhibited good safety in macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provided new insights into the mechanisms of SB216763 in the treatment of pulmonary fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/fcp.70111","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:10:07Z","timestamp":1787098207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Molecular Mechanisms of SB216763 in the Therapeutic Intervention of Pulmonary Fibrosis Based on Macrophage Functional Plasticity\u200c"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9191-2247","authenticated-orcid":false,"given":"Yunuo","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-6375","authenticated-orcid":false,"given":"Jianhong","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2023.08.010"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1300575"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01052-2"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-025-02715-2"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2024.104207"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107798"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1415"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2020.10.008"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.321431"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.153049"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","unstructured":"H. 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