Home >> Research Area >>Others>>GSNOR>> N6022

N6022

GSNOR inhibitor CAS# 1208315-24-5

N6022

Catalog No. BCC4127----Order now to get a substantial discount!

Product Name & Size Price Stock
N6022: 5mg $104 In Stock
N6022: 10mg Please Inquire In Stock
N6022: 20mg Please Inquire Please Inquire
N6022: 50mg Please Inquire Please Inquire
N6022: 100mg Please Inquire Please Inquire
N6022: 200mg Please Inquire Please Inquire
N6022: 500mg Please Inquire Please Inquire
N6022: 1000mg Please Inquire Please Inquire
Related Products
  • SU14813

    Catalog No.:BCC1971
    CAS No.:627908-92-3

Quality Control of N6022

Number of papers citing our products

Chemical structure

N6022

3D structure

Chemical Properties of N6022

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.
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.
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.

Biological Activity of N6022

DescriptionN6022 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:
[1]. Sun X, et al. Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3671-5. [2]. Colagiovanni DB, et al. A nonclinical safety and pharmacokinetic evaluation of N6022: a first-in-class S-nitrosoglutathione reductase inhibitor for the treatment of asthma. Regul Toxicol Pharmacol. 2012 Feb;62(1):115-24. [3]. Green LS, et al. Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry. 2012 Mar 13;51(10):2157-68. [4]. Thomas M. Raffay, et al. Methods of treating respiratory disorders. Patent. US 20170209419 A1.

Protocol

Cell Assay [1]
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.

References:
[1]. Sun X, et al. Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3671-5. [2]. Colagiovanni DB, et al. A nonclinical safety and pharmacokinetic evaluation of N6022: a first-in-class S-nitrosoglutathione reductase inhibitor for the treatment of asthma. Regul Toxicol Pharmacol. 2012 Feb;62(1):115-24. [3]. Green LS, et al. Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry. 2012 Mar 13;51(10):2157-68. [4]. Thomas M. Raffay, et al. Methods of treating respiratory disorders. Patent. US 20170209419 A1.

N6022 Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

N6022 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of N6022

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.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on N6022

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.

Featured Products
New Products
 

References on N6022

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.

Description

N6022 is a selective, and reversible inhibitor of S-nitrosoglutathione reductase (GSNOR) with IC50 of 8 nM and Ki of 2.5 nM. Phase 1/2.

Keywords:

N6022,1208315-24-5,Natural Products,GSNOR, buy N6022 , N6022 supplier , purchase N6022 , N6022 cost , N6022 manufacturer , order N6022 , high purity N6022

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: