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To find prodrugs that can treat inflammation, we performed a preliminary high\u2010throughput screening of 18\u00a0840 small molecular compounds and identified scaffold compound L971 which significantly inhibited JAK\/STAT and NF\u03baB driven luciferase activities. L971 could inhibit the constitutive and stimuli\u2010dependent activation of STAT1, STAT3 and I\u03baB\u03b1 and could significantly down\u2010regulate the proinflammatory gene expression in mouse peritoneal macrophages stimulated by LPS. Gene expression profiles upon L971 treatment were determined using high\u2010throughput RNA sequencing, and significant differentially up\u2010regulated and down\u2010regulated genes were identified by DESeq analysis. The bioinformatic studies confirmed the anti\u2010inflammatory effects of L971. Finally, L971 anti\u2010inflammatory character was further verified in LPS\u2010induced sepsis shock mouse model in vivo. Taken together, these data indicated that L971 could down\u2010regulate both JAK\/STAT and NF\u03baB signalling activities and has the potential to treat inflammatory diseases such as sepsis shock.<\/jats:p>","DOI":"10.1111\/jcmm.16609","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T06:32:31Z","timestamp":1621578751000},"page":"6333-6347","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Scaffold compound L971 exhibits anti\u2010inflammatory activities through inhibition of JAK\/STAT and NF\u03baB signalling pathways"],"prefix":"10.1111","volume":"25","author":[{"given":"Mengyuan","family":"Li","sequence":"first","affiliation":[{"name":"School of Medicine and Pharmacy Ocean University of China Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy Ocean University of China Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Innovation Platform of Marine Drug Screening &amp; Evaluation Qingdao National Laboratory for Marine Science and Technology Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yidan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy Ocean University of China Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohan","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy Ocean University of China Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy Ocean University of China Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangliang","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Life Science Lanzhou University Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy Ocean University of China Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yazhuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy Ocean University of China Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaoling","family":"Song","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy Ocean University of China Qingdao China"},{"name":"Innovation Platform of Marine Drug Screening &amp; Evaluation Qingdao National Laboratory for Marine Science and Technology Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4716-2002","authenticated-orcid":false,"given":"Chenyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy Ocean University of China Qingdao China"},{"name":"Innovation Platform of Marine Drug Screening &amp; Evaluation Qingdao National Laboratory for Marine Science and Technology Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3893"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13320"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/sur.2017.264"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108466"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1714102115"},{"key":"e_1_2_9_7_1","unstructured":"Medicinal and Computational Chemistry Dept. 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