N6022GSNOR inhibitor CAS# 1208315-24-5 |
- SU14813
Catalog No.:BCC1971
CAS No.:627908-92-3
Quality Control & MSDS
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| Cas No. | 1208315-24-5 | SDF | Download SDF |
| PubChem ID | 44623946 | Appearance | Powder |
| Formula | C24H22N4O3 | M.Wt | 414.46 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | Soluble in DMSO > 10 mM | ||
| Chemical Name | 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-imidazol-1-ylphenyl)pyrrol-2-yl]propanoic acid | ||
| SMILES | CC1=C(C=CC(=C1)C(=O)N)N2C(=CC=C2C3=CC=C(C=C3)N4C=CN=C4)CCC(=O)O | ||
| Standard InChIKey | YVPGZQLRPAGKLA-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C24H22N4O3/c1-16-14-18(24(25)31)4-9-21(16)28-20(8-11-23(29)30)7-10-22(28)17-2-5-19(6-3-17)27-13-12-26-15-27/h2-7,9-10,12-15H,8,11H2,1H3,(H2,25,31)(H,29,30) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | N6022 is a potent, selective, reversible, and efficacious S-Nitrosoglutathione reductase(GSNOR) inhibitor with IC50 of 8 nM.In Vitro:N6022 shows concentration-dependent binding to rat plasma proteins. N6022 has more effect on ATP at lower drug concentrations (20 μM) than on GSH[1]. N6022 binds in the GSNO substrate binding pocket like a competitive inhibitor with an IC50 of 8 nM and a Ki of 2.5 nM. N6022 is uncompetitive with cofactors NAD+ and NADH[2].In Vivo:N6022 (50 mg/kg)-treated rats show a slight increase in the incidence of granulomas. In serum, N6022 remains in solution up to 5 mg/mL[1]. References: | |||||
N6022 Dilution Calculator
N6022 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.4128 mL | 12.0639 mL | 24.1278 mL | 48.2556 mL | 60.3195 mL |
| 5 mM | 0.4826 mL | 2.4128 mL | 4.8256 mL | 9.6511 mL | 12.0639 mL |
| 10 mM | 0.2413 mL | 1.2064 mL | 2.4128 mL | 4.8256 mL | 6.0319 mL |
| 50 mM | 0.0483 mL | 0.2413 mL | 0.4826 mL | 0.9651 mL | 1.2064 mL |
| 100 mM | 0.0241 mL | 0.1206 mL | 0.2413 mL | 0.4826 mL | 0.6032 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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N6022 is a specific and fully reversible inhibitor of S-nitrosoglutathione reductase (GSNOR) with IC50 value of 8nM [1].
N6022 is a first-in-class inhibitor of GSNOR. Inhibition of GSNOR causes the accumulation of GSNO which acts as a vasodilator and anti-inflammatory factor. N6022 presents an IC50 value of 8nM in the GSNO reduction assay and 32nM in the HMGSH oxidation assay. The Ki values are 2.5nM and 3.1nM, respectively. N6022 is selective against GSNOR over other human ADH enzymes. The IC50 values are 21μM, 67μM and 0.5μM for ADH IB, ADH II and ADH IV, respectively. N6022 also shows no effect on the NADPH-dependent enzyme, human carbonyl reductase, with IC50 value of 221μM. Currently, N6022 is under clinical studies for the treatment of inflammatory lung diseases [1].
References:
[1] Green L S, Chun L E, Patton A K, et al. Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry, 2012, 51(10): 2157-2168.
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A nonclinical safety and pharmacokinetic evaluation of N6022: a first-in-class S-nitrosoglutathione reductase inhibitor for the treatment of asthma.[Pubmed:22210450]
Regul Toxicol Pharmacol. 2012 Feb;62(1):115-24.
S-nitrosoglutathione reductase is the primary enzyme responsible for the metabolism of S-nitrosoglutathione (GSNO), the body's main source of bioavailable nitric oxide. Through its catabolic activity, GSNO reductase (GSNOR) plays a central role in regulating endogenous S-nitrosothiol levels and protein S-nitrosation-based signaling. By inhibiting GSNOR, we aim to increase pulmonary GSNO and induce bronchodilation while reducing inflammation in lung diseases such as asthma. To support the clinical development of N6022, a first-in-class GSNOR inhibitor, a 14-day toxicology study was conducted. 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. Mechanistic studies showed dose-dependent effects on the integrity of a rat hepatoma cell line.
Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase.[Pubmed:22335564]
Biochemistry. 2012 Mar 13;51(10):2157-68.
N6022 is a novel, first-in-class drug with potent inhibitory activity against S-nitrosoglutathione reductase (GSNOR), an enzyme important in the metabolism of S-nitrosoglutathione (GSNO) and in the maintenance of nitric oxide (NO) homeostasis. Inhibition of GSNOR by N6022 and related compounds has shown safety and efficacy in animal models of asthma, chronic obstructive pulmonary disease, and inflammatory bowel disease [Sun, X., et al. (2011) ACS Med. Chem. Lett. 2, 402-406]. N6022 is currently in early phase clinical studies in humans. We show here that 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). N6022 is uncompetitive with cofactors NAD(+) and NADH. The potency, specificity, and MOI of related GSNOR inhibitor compounds are also reported.
