N6022 | CAS#1208315-24-5 | S-nitrosoglutathione reductase inhibitor

N6022
new

featured

WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 510280

CAS#: 1208315-24-5

Description: N6022 is a potent, selective, reversible, and efficacious S-nitrosoglutathione reductase (GSNOR) inhibitor and is currently undergoing clinical development for the treatment of acute asthma. GSNOR is a member of the alcohol dehydrogenase family (ADH) and regulates the levels of S-nitrosothiols (SNOs) through catabolism of S-nitrosoglutathione (GSNO).

Chemical Structure

N6022

CAS# 1208315-24-5

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 510280
Name: N6022
CAS#: 1208315-24-5
Chemical Formula: C24H22N4O3
Exact Mass: 414.17
Molecular Weight: 414.465
Elemental Analysis: C, 69.55; H, 5.35; N, 13.52; O, 11.58

Price and Availability

Size	Price	Availability	Quantity
100mg	USD 1150
200mg	USD 1650
500mg	USD 2250
1g	USD 3450
2g	USD 5450
5g	USD 8650
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: N6022; N-6022; N 6022.

IUPAC/Chemical Name: 3-(5-(4-(1H-imidazol-1-yl)phenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl)propanoic acid

InChi Key: YVPGZQLRPAGKLA-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: O=C(O)CCC1=CC=C(C2=CC=C(N3C=CN=C3)C=C2)N1C4=CC=C(C(N)=O)C=C4C

Appearance: white to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Reduced levels of GSNO, as well as other nitrosothiols (SNOs), have been implicated in the pathogenesis of many diseases including those of the respiratory, cardiovascular, and gastrointestinal systems. Preservation of endogenous SNOs through GSNOR inhibition presents a novel therapeutic approach with broad applicability. N6022 was demonstrated efficacy in a mouse ovalbumin (OVA) model of asthma. (Bioorg Med Chem Lett. 2011 Oct 1;21(19):5849-53)

Product Data:

Product Data

Instruction:

View handling instruction

Biological target:	N6022 is a potent, selective, reversible, and efficacious S-Nitrosoglutathione reductase(GSNOR) inhibitor with IC50 of 8 nM.
In vitro activity:	This study shows 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. 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). Reference: Biochemistry. 2012 Mar 13;51(10):2157-68. https://pubmed.ncbi.nlm.nih.gov/22335564/
In vivo activity:	In a mouse model of ovalbumin-induced asthma, N6022 attenuated methacholine-induced bronchoconstriction (airway hyperresponsiveness) in a dose- and time-dependent manner, with significant efficacy achieved with a single IV dose ≥0.01 mg/kg and when administered from 30 min to 48 h prior to the methacholine challenge. N6022 also significantly attenuated eosinophil infiltration into the lungs with a single IV dose ≥0.0005 mg/kg. Reference: ACS Med Chem Lett. 2011 Mar 11;2(5):402-6. https://pubmed.ncbi.nlm.nih.gov/24900320/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	30.0	72.38
	DMSO	52.7	127.07
	Ethanol	1.0	2.41
	PBS (pH 7.2)	0.1	0.24

Preparing Stock Solutions

The following data is based on the product molecular weight 414.47 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	1. Green LS, Chun LE, Patton AK, Sun X, Rosenthal GJ, Richards JP. Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry. 2012 Mar 13;51(10):2157-68. doi: 10.1021/bi201785u. Epub 2012 Feb 28. PMID: 22335564. 2. Jiao L, Su LY, Liu Q, Luo R, Qiao X, Xie T, Yang LX, Chen C, Yao YG. GSNOR deficiency attenuates MPTP-induced neurotoxicity and autophagy by facilitating CDK5 S-nitrosation in a mouse model of Parkinson's disease. Free Radic Biol Med. 2022 Aug 20;189:111-121. doi: 10.1016/j.freeradbiomed.2022.07.016. Epub 2022 Jul 30. PMID: 35918012. 3. Sun X, Wasley JW, Qiu J, Blonder JP, Stout AM, Green LS, Strong SA, Colagiovanni DB, Richards JP, Mutka SC, Chun L, Rosenthal GJ. Discovery of s-nitrosoglutathione reductase inhibitors: potential agents for the treatment of asthma and other inflammatory diseases. ACS Med Chem Lett. 2011 Mar 11;2(5):402-6. doi: 10.1021/ml200045s. PMID: 24900320; PMCID: PMC4018076.
In vitro protocol:	1. Green LS, Chun LE, Patton AK, Sun X, Rosenthal GJ, Richards JP. Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry. 2012 Mar 13;51(10):2157-68. doi: 10.1021/bi201785u. Epub 2012 Feb 28. PMID: 22335564.
In vivo protocol:	1. Jiao L, Su LY, Liu Q, Luo R, Qiao X, Xie T, Yang LX, Chen C, Yao YG. GSNOR deficiency attenuates MPTP-induced neurotoxicity and autophagy by facilitating CDK5 S-nitrosation in a mouse model of Parkinson's disease. Free Radic Biol Med. 2022 Aug 20;189:111-121. doi: 10.1016/j.freeradbiomed.2022.07.016. Epub 2022 Jul 30. PMID: 35918012. 2. Sun X, Wasley JW, Qiu J, Blonder JP, Stout AM, Green LS, Strong SA, Colagiovanni DB, Richards JP, Mutka SC, Chun L, Rosenthal GJ. Discovery of s-nitrosoglutathione reductase inhibitors: potential agents for the treatment of asthma and other inflammatory diseases. ACS Med Chem Lett. 2011 Mar 11;2(5):402-6. doi: 10.1021/ml200045s. PMID: 24900320; PMCID: PMC4018076.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.

Mass

Concentration

Volume

M. Wt* g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Dilution Calculator

Calculate the dilution required to prepare a stock solution.

Concentration 1

Volume 1

Concentration 2

Volume 2

1: Blonder JP, Mutka SC, Sun X, Qiu J, Green LH, Mehra NK, Boyanapalli R, Suniga M, Look K, Delany C, Richards JP, Looker D, Scoggin C, Rosenthal GJ. Pharmacologic inhibition of S-nitrosoglutathione reductase protects against experimental asthma in BALB/c mice through attenuation of both bronchoconstriction and inflammation. BMC Pulm Med. 2014 Jan 10;14:3. doi: 10.1186/1471-2466-14-3. PubMed PMID: 24405692; PubMed Central PMCID: PMC3893392.

2: Sun X, Qiu J, Strong SA, Green LS, Wasley JW, Blonder JP, Colagiovanni DB, Stout AM, Mutka SC, Richards JP, Rosenthal GJ. Structure-activity relationship of pyrrole based S-nitrosoglutathione reductase inhibitors: carboxamide modification. Bioorg Med Chem Lett. 2012 Mar 15;22(6):2338-42. doi: 10.1016/j.bmcl.2012.01.047. Epub 2012 Feb 2. PubMed PMID: 22342142.

3: Green LS, Chun LE, Patton AK, Sun X, Rosenthal GJ, Richards JP. Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry. 2012 Mar 13;51(10):2157-68. doi: 10.1021/bi201785u. Epub 2012 Feb 28. PubMed PMID: 22335564.

4: Colagiovanni DB, Drolet DW, Langlois-Forget E, PichÃ© MP, Looker D, Rosenthal GJ. 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. doi: 10.1016/j.yrtph.2011.12.012. Epub 2011 Dec 24. PubMed PMID: 22210450.

5: Sun X, Qiu J, Strong SA, Green LS, Wasley JW, Blonder JP, Colagiovanni DB, Mutka SC, Stout AM, Richards JP, Rosenthal GJ. Discovery of potent and novel S-nitrosoglutathione reductase inhibitors devoid of cytochrome P450 activities. Bioorg Med Chem Lett. 2011 Oct 1;21(19):5849-53. doi: 10.1016/j.bmcl.2011.07.103. Epub 2011 Aug 3. PubMed PMID: 21855338.

6: Sun X, Qiu J, Strong SA, Green LS, Wasley JW, Colagiovanni DB, Mutka SC, Blonder JP, Stout AM, Richards JP, Chun L, Rosenthal GJ. 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. doi: 10.1016/j.bmcl.2011.04.086. Epub 2011 Apr 24. PubMed PMID: 21570838.

Your view history

N6022 new featured