ChREBP drives diabetic kidney disease, and its inhibition confers renal protection.

ChREBP-dependent transcriptional activity is markedly up-regulated in diabetic kidneys of DKD model mice, and genetic loss of ChREBP ameliorates DKD.

• Why it matters: Intracellular pathways that could be pharmacologically targeted in diabetic kidney disease are poorly defined, limiting mechanism-based therapies.
• What they did: Transcriptome screening in DKD model mice identified a ChREBP-dependent cascade; a chemical screen then found D-532, which inhibits ChREBP transcriptional activity in human and rodent cells.
• The result: Oral D-532 protected multiple diabetic mouse models from DKD progression by suppressing ChREBP and downstream targets linked to excessive reactive oxygen species production, supporting ChREBP as a druggable driver.

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