Sivelestat (ONO5046) is a potent and selective inhibitor of neutrophil elastase with IC50 of 44 nM.

Neutrophil elastase:44 nM.

Sivelestat 通过抑制 NF-kB 的活性，降低炎症介质的水平，并在促炎细胞因子刺激的肝细胞中抑制 iNOS 基因的表达。此外，它还能抑制 NE 刺激下 TGF-α 的释放，从而抑制胃癌细胞的生长。

给予sivelestat能够减轻小鼠急性肺损伤后的肺纤维化。Sivelestat还能减轻大鼠脓毒症相关的肾损伤。它通过阻断GAPDH/Siah1这一新型信号通路，从而减轻脊髓损伤的进展。

TMK-1 Gastric carcinoma cells are seeded into 96-well culture plates (5 ×103 cells/well) in RPMI containing 7% FBS, 2.0 mM L-glutamine, and 1% nonessential amino acids. Following 24-h incubation in RPMI-1640 medium with 5% FBS, the cells are incubated for 24, 48 or 72 h at 37°C in a humidified atmosphere of 5% CO2 with varied concentrations (0.1–1.0 μg/mL) of NE, or with varied concentrations (0.1–1000 μg/mL) of sivelestat or with concentrations (10 and 100 ng/mL) of anti-TGF-α antibody in the presence of 1 μg/mL NE. After incubation, 10 μL of MTT solution (5 mg/mL) is added to each well and the plates are then incubated for 3 h at 37°C. The growth medium is then replaced with 150 μL of dimethyl sulfoxide (Wako) per well and the absorbance at 540 nm is measured.

Animal Models: Male Sprague-Dawley rats. Formulation: Saline. Dosages: 50 or 100 mg/kg. Administration: i.p.