HMGB1-IN-2 (compound 15) is an inhibitor of highly conserved nuclear protein (HMGB1), showing NO inhibitory effect with IC 50 value of 20.2 μM in RAW264.7 cells. HMGB1-IN-2 (30 μM) decreases the level of IL-1 β, TNF-α, caspase-1 p20, inhibits the phosphorylation of NF-κB p65, exhibits anti-apoptotic activity. HMGB1-IN-2 (15 mg/kg; ip) relives kidney injury in septic acute kidney injury mouse. HMGB1-IN-2 inhibits Huh7 cells and A549 cells with IC 50 s of 77.0 μM, and 82.0 μM, respectively.