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In this study, a series of chromone derivatives were designed and synthesized. Additionally, we established a NOX4 overexpression model using the NRK\u201049F rat renal fibroblasts cell line and identified compound <jats:bold>14m<\/jats:bold> as highly active through the assessment of intracellular reactive oxygen species (ROS) levels in this model. The drug affinity responsive target stability (DARTS) assay illuminated the robust binding stability of <jats:bold>14m<\/jats:bold> with NOX4. Mechanistic studies further substantiated its efficacy in ameliorating fibrosis and inflammation. This investigation positions <jats:bold>14m<\/jats:bold> as a noteworthy NOX4 inhibitor, shedding light on its regulatory role in renal fibroblasts. Importantly, it diversifies the structural landscape of NOX4 inhibitors, offering novel lead compounds for future development.<\/jats:p>","DOI":"10.1111\/cbdd.70015","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T02:14:33Z","timestamp":1731550473000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Chromone Derivatives as a Novel NOX4 Inhibitor: Design, Synthesis, and Regulation of ROS in Renal Fibroblast"],"prefix":"10.1111","volume":"104","author":[{"given":"Siming","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Xiangya School of Pharmaceutical Sciences Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Organ Fibrosis  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicinal 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