N6022

• CAT Number: I000781
• CAS Number: 1208315-24-5
• Molecular Formula: C24H22N4O3
• Molecular Weight: 414.5
• Purity: ≥95%
• Target: GSNOR
• Solubility: DMSO: ≥ 46 mg/mL
• Storage: Store at -20C
• IC50: 10 nM [1]
• InChIKey: YVPGZQLRPAGKLA-UHFFFAOYSA-N

N6022 is a potent, selective, reversible, and efficacious S-Nitrosoglutathione reductase(GSNOR) inhibitor(IC50=10 nM) which is currently undergoing clinical development.IC50 value: 10 nM [1]Target: GSNORin vitro: N6022 is a tight-binding, specific, and fully reversible inhibitor of GSNOR with an IC(50) of 8 nM and a K(i) of 2.5 nM. We accounted for the fact that the NAD(+)- and NADH-dependent oxidation and reduction reactions, catalyzed by GSNOR are bisubstrate in nature in our calculations. N6022 binds in the GSNO substrate binding pocket like a competitive inhibitor, although in kinetic assays it behaves with a mixed uncompetitive mode of inhibition (MOI) toward the GSNO substrate and a mixed competitive MOI toward the formaldehyde adduct, S-hydroxymethylglutathione (HMGSH) [3].in vivo:Sprague-Dawley rats were given 2, 10 or 50 mg/kg/day N6022 via IV administration. N6022 was well tolerated at all doses and no biologically significant adverse findings were noted in the study up to 10 mg/kg/day. N6022-related study findings were limited to the high dose group. One male rat had mild hepatocellular necrosis with accompanying increases in ALT and AST and several male animals had histological lung assessments with a slight increase in foreign body granulomas. Systemic exposure was greater in males than females and saturation of plasma clearance was observed in both sexes in the high dose group. Liver was identified as the major organ of elimination [2].

Reference

1:Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Green LS, Chun LE, Patton AK, Sun X, Rosenthal GJ, Richards JP.Biochemistry. 2012 Mar 13;51(10):2157-68. doi: 10.1021/bi201785u. Epub 2012 Feb 28. PMID: 22335564 2:A nonclinical safety and pharmacokinetic evaluation of N6022: a first-in-class S-nitrosoglutathione reductase inhibitor for the treatment of asthma. Colagiovanni DB, Drolet DW, Langlois-Forget E, Piché MP, Looker D, Rosenthal GJ.Regul Toxicol Pharmacol. 2012 Feb;62(1):115-24. doi: 10.1016/j.yrtph.2011.12.012. Epub 2011 Dec 24. PMID: 22210450