S-Nitrosoglutathione reductase (GSNOR) is a zinc-dependent, NAD+- and NADH-dependent, medium chain alcohol dehydrogenase (ADH) that plays an important role in nitrosative biology by metabolizing the S-nitrosothiol, GSNO. N6022 is a potent, selective and reversible GSNOR inhibitor with an IC50 of 8 nM and a Ki of 2.5 nM[3]. In cytochrome P450 assays, N6022 potently inhibited CYP2C19 with an IC50 of 0.77 μM. And it exhibited minimal cytotoxicity (IC50 > 100 μM) toward A549 epithelial lung cells. In a mouse model of ovalbumin-induced asthma, N6022 attenuated methacholine-induced broncho-constriction (airway hyperresponsiveness) in a dose- and time-dependent manner, with significant efficacy achieved with a single IV dose ≥0.01 mg/kg[4].
作用机制
N6022 binds in the GSNO substrate binding pocket like a competitive inhibitor[3].
搜索
