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

Neutrophil elastase:44 nM.

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.

西维来司他, ONO5046, LY544349, EI546

Ethanol: 80 mg/mL (184.14 mM), Sonication is recommended.

H2O: < 1 mg/mL (insoluble)

DMSO: 45 mg/mL (103.58 mM), Sonication is recommended.

10% DMSO+40% PEG300+5% Tween 80+45% Saline: 2 mg/mL (4.6 mM), Sonication is recommended.