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Through enzymatic assessments, the superior compound <jats:bold>12a<\/jats:bold> with an IC<jats:sub>50<\/jats:sub> value of 12.6\u2009nM against JAK1 was identified and a 10.7\u2010fold selectivity index over JAK2 was achieved. It was indicated that <jats:bold>12a<\/jats:bold> displayed considerable effect in inhibiting the pro\u2010inflammatory NO generated from lipopolysaccharide (LPS)\u2010induced RAW264.7 macrophages, while on normal RAW264.7 cells, <jats:bold>12a<\/jats:bold> exerted a weak cytotoxicity effect (IC<jats:sub>50<\/jats:sub>\u2009=\u2009143.3\u2009\u03bcM). Furthermore, H&amp;E stain assay demonstrated the conspicuous capacity of <jats:bold>12a<\/jats:bold> to suppress CCl<jats:sub>4<\/jats:sub>\u2010induced hepatic fibrosis levels in a dose\u2010dependent manner in vivo. The binding model of <jats:bold>12a<\/jats:bold> ideally reflects the excellent activity of JAK1 over the homologous kinase JAK2. Overall, <jats:bold>12a<\/jats:bold>, a JAK1\u2010selective inhibitor, exhibited potential for liver fibrosis and inflammatory diseases.<\/jats:p>","DOI":"10.1002\/ardp.202300591","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T03:15:44Z","timestamp":1704683744000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Structure\u2010guided design of potent JAK1\u2010selective inhibitors based on 4\u2010amino\u20107<i>H<\/i>\u2010pyrrolo[2,3\u2010<i>d<\/i>]pyrimidine with anti\u2010inflammatory efficacy"],"prefix":"10.1002","volume":"357","author":[{"given":"Jiahao","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Structure\u2010Based Drug Design and Discovery, Ministry of Education Shenyang Pharmaceutical University Shenyang 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