What question did this study set out to answer?

The aim is to develop a safer prodrug of bardoxolone methyl for treating acute lung injury.

April 1, 2026ChemMedChem0 citations

Discovery of a Prodrug of Bardoxolone Methyl for the Treatment of Acute Lung Injury

Key Points

The aim is to develop a safer prodrug of bardoxolone methyl for treating acute lung injury.
Synthesized a H2O2-sensitive prodrug of CDDO-Me.
Tested cytotoxicity in RAW 264.7 cells.
Evaluated NO production inhibition in LPS-stimulated cells.
Assessed therapeutic effects in an acute lung injury mouse model.
Prodrug 2 showed lower cytotoxicity compared to CDDO-Me.
Demonstrated concentration-dependent inhibition of NO production.
Achieved therapeutic efficacy comparable to CDDO-Me in animal models.
Significantly reduced LPS-induced lung injury symptoms.

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.

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