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N6022

Catalog No.
B1111
GSNOR inhibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$175.00
In stock
5mg
$103.00
In stock
25mg
$334.00
In stock
100mg
$698.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt414.46
Cas No.1208315-24-5
FormulaC24H22N4O3
Solubilityinsoluble in EtOH; insoluble in H2O; ≥20.7 mg/mL in DMSO
Chemical Name3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-imidazol-1-ylphenyl)pyrrol-2-yl]propanoic acid
SDFDownload SDF
Canonical SMILESCC1=C(C=CC(=C1)C(=O)N)N2C(=CC=C2C3=CC=C(C=C3)N4C=CN=C4)CCC(=O)O
Shipping ConditionEvaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.

Protocol

Kinase experiment [1]:

Alcohol dehydrogenase (ADH) Enzyme Assays

For ADH IB, ADH II, and ADH IV assays, enzyme activity was determined by measuring the increase in A340 due to reduction of NAD+ to NADH using conditions similar to those described by Sanghani et al. N6022 was dissolved and diluted in a PBS solution containing 1 N NaOH (1%). The IC50 values for N6022 versus ADH IB and ADH II were determined with ethanol as the substrate. The final assay conditions for ADH IB were 50 mM sodium phosphate (pH 7.4), 20 μg/mL ADH IB, 2 mM NAD+, and 2 mM ethanol, and the final assay conditions for ADH II were 90 mM sodium pyrophosphate (pH 8.9), 4.4 μg/mL ADH II, 23.6 mM NAD+, and 14.4 mM ethanol. The IC50 value of N6022 against ADH IV was determined using hexanol as a substrate. The hexanol was first dissolved in DMSO so that it could be dissolved in assay buffer. The final assay conditions were 50 mM sodium phosphate (pH 7.4), 1.25 μg/mL ADH IV, 2 mM NAD+, 400 μM hexanol, and 1% DMSO.

Animal experiment [2]:

Animal models

Female BALB/c mice model

Dosage form

0.1 mg/kg to 10 mg/kg, i.v. for 1-48 h

Applications

N6022 dose-dependently decreased enhanced pause (Penh) and Bronchoalveolar lavage fluid (BALF) eosinophils, increased bronchoalveolar lavage fluid (BALF) nitrite and plasma cyclic guanosine monophosphate (cGMP) in ovalbumin (OVA)-sensitized mice. Moreover, N6022 attenuated the OVA-induced increase in nuclear factor kappa B (NFκB) activation and decreased methacholine (MCh)-induced contraction in isolated rat tracheal rings.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

1. Green, L. S., Chun, L. E., Patton, A. K., Sun, X., Rosenthal, G. J. and Richards, J. P. (2012) Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry. 51, 2157-21682

2. Blonder, J. P., Mutka, S. C., Sun, X., Qiu, J., Green, L. H., Mehra, N. K., Boyanapalli, R., Suniga, M., Look, K., Delany, C., Richards, J. P., Looker, D., Scoggin, C. and Rosenthal, G. J. (2014) Pharmacologic inhibition of S-nitrosoglutathione reductase protects against experimental asthma in BALB/c mice through attenuation of both bronchoconstriction and inflammation. BMC Pulm Med. 14, 3

Quality Control

Chemical structure

N6022