N6022(IC50 of 8 nM) is an effective, reversible, and selective S-Nitrosoglutathione reductase(GSNOR) inhibitor.

GSNOR:8 nM

N6022 binds to rat plasma proteins in a concentration-dependent manner. At lower drug concentrations (20 μM), N6022 show more effect on ATP than on GSH. N6022 (IC50 of 8 nM and a Ki of 2.5 nM) binds in the GSNO substrate binding pocket like a competitive inhibitor. N6022 is uncompetitive with cofactors NAD+ and NADH.

N6022 treats rats in 50 mg/kg leading to a slight increase in the incidence of granulomas. In serum, N6022 remained in solution is up to 5 mg/mL.

N6022 is dissolved in 5% DMSO. N6022 is tested using a rat hepatoma (H4IIE) cell line whereby cells are seeded into 96-well plates and cultured in medium containing 20% bovine serum. Following an equilibration period of 48 h, the cells are treated with N6022 (5% DMSO vehicle) at concentrations of 0, 1, 5, 10, 20, 50, 100, and 300 μM for 24 h at 37°C in 5% CO2. Camptothecin and rotenone are included as positive controls. The cell supernatant or the cells themselves are harvested for biochemical analysis.