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However, concerns regarding safety and tissue specificity still remain. Herein, we designed and synthesized an H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010sensitive CDDO\u2010Me prodrug\n                    <jats:bold>2<\/jats:bold>\n                    . Results indicated that prodrug\n                    <jats:bold>2<\/jats:bold>\n                    can be activated by H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    and exhibited the high drug release rate. In RAW 264.7 cells, prodrug\n                    <jats:bold>2<\/jats:bold>\n                    demonstrated lower cytotoxicity compared to CDDO\u2010Me. Moreover, prodrug\n                    <jats:bold>2<\/jats:bold>\n                    concentration\u2010dependently inhibited NO production in lipopolysaccharide (LPS)\u2010stimulated cells. In an ALI mouse model, prodrug\n                    <jats:bold>2<\/jats:bold>\n                    exhibited therapeutic efficacy comparable to CDDO\u2010Me and significantly attenuated the symptoms of LPS\u2010induced lung injury.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202501062","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:10:12Z","timestamp":1774941012000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Discovery of a Prodrug of Bardoxolone Methyl for the Treatment of Acute Lung Injury"],"prefix":"10.1002","volume":"21","author":[{"given":"Shuai","family":"Wen","sequence":"first","affiliation":[{"name":"College of Pharmacy Taizhou University  Taizhou China"},{"name":"Jiangsu Key Laboratory of Drug Design and Optimization China Pharmaceutical University  Nanjing 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