Discovery of a Prodrug of Bardoxolone Methyl for the Treatment of Acute Lung Injury
Abstract
Bardoxolone methyl, also known as CDDO‐Me, has demonstrated protective and therapeutic effects on a variety of lung diseases, especially showing great promise for the treatment of acute lung injury (ALI). However, concerns regarding safety and tissue specificity still remain. Herein, we designed and synthesized an H 2 O 2 ‐sensitive CDDO‐Me prodrug 2 . Results indicated that prodrug 2 can be activated by H 2 O 2 and exhibited the high drug release rate. In RAW 264.7 cells, prodrug 2 demonstrated lower cytotoxicity compared to CDDO‐Me. Moreover, prodrug 2 concentration‐dependently inhibited NO production in lipopolysaccharide (LPS)‐stimulated cells. In an ALI mouse model, prodrug 2 exhibited therapeutic efficacy comparable to CDDO‐Me and significantly attenuated the symptoms of LPS‐induced lung injury.
Fields of Study & Subjects
Genomics
phytochemicals
and oxidative stress
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Electron Spin Resonance Studies
Publication details
- Journal / source
- ChemMedChem
- Publisher
- Wiley
- Volume
- 21
- Issue
- 6
- Pages
- e202501062–e202501062
- Publication date
- 27 March 2026
- Language
- EN