HMGB1-IN-2 (compound 15) is a selective inhibitor of the highly conserved nuclear protein HMGB1, showing no inhibitory effect at an IC50 of 20.2 µM in RAW264.7 cells. At 30 µM, it reduces IL-1beta, TNF-alpha, and caspase-1 p20 levels, inhibits NF-kappaB p65 phosphorylation, and provides anti-apoptotic effects. In vivo, 15 mg/kg of HMGB1-IN-2 administered intraperitoneally alleviates kidney injury in a mouse model of septic acute kidney injury. Additionally, it inhibits Huh7 and A549 cells with IC50 values of 77.0 µM and 82.0 µM, respectively [1].
