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

MedKoo Cat#: 510280 | Name: N6022

Description:

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

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

Theoretical Analysis

MedKoo Cat#: 510280

Name: N6022

CAS#: 1208315-24-5

Chemical Formula: C24H22N4O3

Exact Mass: 414.1692

Molecular Weight: 414.47

Elemental Analysis: C, 69.55; H, 5.35; N, 13.52; O, 11.58

Price and Availability

Size	Price	Availability
100mg	USD 1,150.00	2 Weeks
200mg	USD 1,650.00	2 Weeks
500mg	USD 2,250.00	2 Weeks
1g	USD 3,450.00	2 Weeks
2g	USD 5,450.00	2 Weeks
5g	USD 8,650.00	2 Weeks

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Related CAS #

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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/

	Solvent	mg/mL	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

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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:

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.

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.