S-nitrosothiol (N6022) News

|||||||||| morphine sulphate / Generic mfg., S-nitrosothiol (N6022) / Laurel Venture Capital
Journal: Opioid prescribing patterns following surgical interventions for benign prostatic hyperplasia. (Pubmed Central) - Apr 10, 2025
Despite similar cumulative opioid use, differences in prescription rates indicate a need for improved postoperative pain management strategies, possibly using non-opioid alternatives. Future research should focus on optimizing pain control, characterizing actual opioid consumption, and considering patient-specific factors in surgical decision-making.

|||||||||| S-nitrosothiol (N6022) / Laurel Venture Capital
Preclinical, Journal: Novel Pathways of Oxidative and Nitrosative Inactivation of the Human MGMT Protein in Colon Cancer and Glioblastoma Cells: Increased Efficacy of Alkylating Agents In Vitro and In Vivo. (Pubmed Central) - Feb 25, 2025
N6022 treatment increased the presence of nitrosylated MGMT for a longer time, thereby extending the DNA-repair deficient state both in cell culture and preclinical settings. Our findings highlight the options for redox-driven therapeutic strategies for MGMT and suggest that oxidative and/or nitrosative inactivation of DNA repair in combination with alkylating agents could be exploited.

|||||||||| cavosonstat (PBA-003) / Laurel Therap, Path BioAnalytics, S-nitrosothiol (N6022) / Laurel Venture Capital
Journal: The role of S-nitrosoglutathione reductase (GSNOR) in T cell-mediated immunopathology of experimental autoimmune encephalomyelitis (EAE). (Pubmed Central) - Nov 14, 2024
This observation underscores the potential of increased GSNOR expression and activity as a risk factor exacerbating EAE immunopathology, while simultaneously highlighting its potential as a target for modifying the disease. Furthermore, the balanced immune regulation provided by orally active N91115 (IL-6/IL-17a vs. IL-10) presents a promising alternative to immunosuppressive drugs, reducing the risk of opportunistic infections.

|||||||||| S-nitrosothiol (N6022) / Laurel Venture Capital
Preclinical, Journal: Sterile inflammation induces vasculopathy and chronic lung injury in murine sickle cell disease. (Pubmed Central) - Mar 25, 2024
SS mice were treated with either phosphate-buffered saline (PBS), hE-HMGB1-BP, an hE dual-domain peptide that binds and removes HMGB1 from the circulation via the liver, 1-[4-(aminocarbonyl)-2-methylphenyl]-5-[4-(1H-imidazol-1-yl)phenyl]-1H-pyrrole-2-propanoic acid (N6022) or N-acetyl-lysyltyrosylcysteine amide (KYC) for three weeks...The marked changes in pulmonary morphometrics and GSNOR expression throughout the lung parenchyma in SS mice were improved by treating with either hE-HMGB1-BP or KYC. These data demonstrate that murine SCD induces vasculopathy and chronic lung disease by an HMGB1- and GSNOR-dependent mechanism and suggest that HMBG1 and GSNOR might be effective therapeutic targets for reducing vasculopathy and chronic lung disease in humans with SCD.

|||||||||| S-nitrosothiol (N6022) / Laurel Venture Capital
Journal: The Crucial Role of SlGSNOR in Regulating Postharvest Tomato Fruit Ripening. (Pubmed Central) - Mar 17, 2024
In addition, the endogenous NO contents were elevated by 197.55%; 404.59%; and 713.46%, and the endogenous SNOs contents were enhanced by 74.65%; 93.49%; and 94.85%; by N6022 and GSNO treatments and SlGSNOR silencing, respectively. Altogether, these results indicate that SlGSNOR positively promotes tomato postharvest fruit ripening, which may be largely on account of its negative roles in the endogenous NO level.

|||||||||| S-nitrosothiol (N6022) / Laurel Venture Capital
Nitric Oxide Synthase Modulates the S-Nitrosoglutathione Reductase Inhibitor Rescue of Neonatal Oxygen-Induced Airway Hyperreactivity in Murine Precision-cut Lung Slices (Convention Center Exhibit Hall) - Mar 16, 2024 - Abstract #PAS2024PAS_3644;
Pre-incubation of hyperoxic slices with either L-NAME or DTT rendered the GSNOR inhibitor ineffective in rescuing airway responses to the maximal dose of MCh compared to vehicle (Fig 2). Conclusion(s): These studies show that neonatal hyperoxia-exposed mice display in vitro AHR to MCh and that inhibition of GSNOR attenuates oxygen-induced AHR.

|||||||||| S-nitrosothiol (N6022) / Laurel Venture Capital
Preclinical, Journal: Efficacies of S-nitrosoglutathione (GSNO) and GSNO reductase inhibitor in SARS-CoV-2 spike protein induced acute lung disease in mice. (Pubmed Central) - Dec 25, 2023
Optimization of GSNO by treatment with exogenous GSNO or inhibition of GSNOR by N6022 (or GSNO knockout) protects against SP-S1-induced lung diseases in both genders. These findings provide evidence for the potential efficacies of GSNO and GSNOR inhibitors in addressing the multi-mechanistic nature of SARS-CoV-2 SP-associated acute-lung disease.

|||||||||| S-nitrosothiol (N6022) / Laurel Venture Capital
Journal: Mechanistic study of the Aldo-keto reductase family 1 member A1 in regulating mesenchymal stem cell fate decision toward adipogenesis and osteogenesis. (Pubmed Central) - Dec 25, 2023
More importantly, Akr1A1 was identified as a new key regulator for controlling the MSC lineage commitment in favor of adipogenesis but detrimental to osteogenesis. Such information should be useful to develop perspective new therapeutic agents to reverse the adipo-osteogenic differentiation of BMSCs, in a way to increase in osteogenesis but decrease in adipogenesis.

|||||||||| S-nitrosothiol (N6022) / Alpine Immune Sci
Preclinical, Journal: GSNOR deficiency attenuates MPTP-induced neurotoxicity and autophagy by facilitating CDK5 S-nitrosation in a mouse model of Parkinson's disease. (Pubmed Central) - Aug 18, 2022
Mechanistically, deficiency of GSNOR inhibited MPTP-induced CDK5 kinase activity and CDK5-mediated autophagy by increasing S-nitrosation of CDK5 at Cys83. Our study indicated that GSNOR is a key regulator of CDK5 S-nitrosation and is actively involved in CDK5-mediated autophagy induced by MPTP.

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Journal: GABA keeps nitric oxide in balance by regulating GSNOR to enhance disease resistance of harvested tomato against Botrytis cinerea. (Pubmed Central) - Jun 22, 2022
The endogenous NO level was excessively high after treatment with a GSNOR scavenger, N6022, making the fruit more susceptible to pathogen...However, overexpression of SlGSNOR exhibited opposite consequences. These results suggest that a suitable level of NO is beneficial for enhancing disease resistance, and GABA can help tomatoes maintain NO equilibrium by regulating GSNOR.

|||||||||| S-nitrosothiol (N6022) / Alpine Immune Sci
Journal: GSNOR and ALDH2 alleviate traumatic spinal cord injury. (Pubmed Central) - Jan 4, 2022
Combining the specific inhibitor of GSNOR (N6022) with the selective activator of ALDH2 (Alda-1) provides greater protection to the neurovascular unit and confers greater functional recovery. The study is novel, and the combination therapy (N6022+Alda-1) possesses translational potential.

|||||||||| S-nitrosothiol (N6022) / Alpine Immune Sci
Journal: GSNOR facilitates antiviral innate immunity by restricting TBK1 cysteine S-nitrosation. (Pubmed Central) - Dec 2, 2021
Mechanistically, GSNOR deficiency enhanced cellular TANK-binding kinase 1 (TBK1) protein S-nitrosation at the Cys423 site and inhibited TBK1 kinase activity, resulting in reduced interferon production for antiviral responses. Our study indicated that GSNOR is a critical regulator of antiviral responses and S-nitrosation is actively involved in innate immunity.

|||||||||| S-nitrosothiol (N6022) / Alpine Immune Sci
Journal: Fluorescein isothiocyanate, a platform for the selective and sensitive detection of S-Nitrosothiols and hydrogen sulfide. (Pubmed Central) - Nov 13, 2021
FDTC was tested as an intracellular RSNO-sensor in germinating tomato seedlings (Solanum lycopersicum) via epifluorescence microscopy. Control plant roots exposed to FDTC showed low intracellular fluorescence which increased ∼3-fold upon exposure to extracellular S-nitrosoglutathione and ∼4-fold in the presence of N6022, a S-nitrosoglutathione reductase (GSNOR) inhibitor, demonstrating that FDTC can be used to visualize intracellular RSNO levels.

|||||||||| S-nitrosothiol (N6022) / Alpine Immune Sci
Preclinical, Journal: Targeting GSNOR for functional recovery in a middle-aged mouse model of stroke. (Pubmed Central) - Sep 3, 2021
These results are the first evidence of a new pathway for the treatment of stroke via the inhibition of GSNOR. Based on the efficacy of N6022 in the stroke animal model and its use in human therapeutic studies without toxicity, we submit that GSNOR is a druggable target, and N6022 is a promising drug candidate for human stroke therapy.

|||||||||| S-nitrosothiol (N6022) / Alpine Immune Sci
Journal: Regulation of B cell functions by S-nitrosoglutathione in the EAE model. (Pubmed Central) - Jul 29, 2021
Adoptive transfer of B cells from N6022 treated EAE mice or EAE mice deficient in the GSNOR gene also regulated T cell balance (Treg > Th17) and reduced clinical disease in the recipient EAE mice. The data presented here provide evidence of the role of GSNO in shifting B cell immune balance (IL-10 > IL-6) and the preclinical relevance of N6022, a first-in-class drug targeting GSNOR with proven human safety, as therapeutics for autoimmune disorders including multiple sclerosis.

|||||||||| sildenafil / Generic mfg.
Clinical, Journal: The CoDiNOS trial protocol: an international randomised controlled trial of intravenous sildenafil versus inhaled nitric oxide for the treatment of pulmonary hypertension in neonates with congenital diaphragmatic hernia. (Pubmed Central) - Nov 21, 2020
Parental informed consent will be obtained. NTR6982; Pre-results.

|||||||||| s-nitrosoglutathione (N30-201) / Alpine
Journal: Tomato Root Growth Inhibition by Salinity and Cadmium Is Mediated By S-Nitrosative Modifications of ROS Metabolic Enzymes Controlled by S-Nitrosoglutathione Reductase. (Pubmed Central) - Sep 13, 2020
An opposite effect occurred in cultivated S. lycopersicum, where reduced GSNOR activity and intensive S-nitrosation resulted in reduced ROS levels by abiotic stress. These data suggest stress-triggered disruption of ROS homeostasis, mediated by modulation of RNS and S-nitrosation of NADPHox and APX, underlies tomato root growth inhibition by salinity and cadmium stress.

|||||||||| s-nitrosoglutathione (N30-201) / Alpine
Journal: Exogenous Nitric Oxide Enhances Disease Resistance by Nitrosylation and Inhibition of S-Nitrosoglutathione Reductase in Peach Fruit. (Pubmed Central) - Jul 17, 2020
Moreover, NO and GSNOR inhibitor enhanced the expression of systemic acquired resistance (SAR)-related genes, such as pathogenesis-related gene 1 (PR1), nonexpressor of PR1 (NPR1), and TGACG-binding factor 1 (TGA1). These results demonstrated that S-nitrosylation of GSNOR protein and inhibition of GSNOR activity contributed to the enhanced disease resistance in fruit.

|||||||||| s-nitrosoglutathione (N30-201) / Alpine
Preclinical, Journal: S-Nitrosoglutathione Mimics the Beneficial Activity of Endothelial Nitric Oxide Synthase-Derived Nitric Oxide in a Mouse Model of Stroke. (Pubmed Central) - Feb 7, 2020
Reduced brain infarctions and edema, and improved neurobehavioral functions by pre- or postinjury GSNO treatment of eNOS knock out mice indicate that GSNO can attenuate IR injury, likely by mimicking the eNOS-derived NO-dependent anti-ischemic and anti-inflammatory functions. Neurovascular protection by GSNO/N6022 in both pre- and postischemic injury groups support GSNO as a promising drug candidate for the prevention and treatment of stroke injury.

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Inhibition of S-nitrosoglutathione Reductase Improves Stroke Outcomes and Stimulates Functional Recovery in an Aged Mouse Model of Stroke (Hall H) - Dec 21, 2019 - Abstract #ISC2020ISC_1861;
These results are the first evidence of a new pathway to treat stroke via the inhibition of GSNOR. Based on the efficacy of N6022 in this stroke animal model and its use in humans without toxicity in other indications, we submit that GSNOR is a druggable target and N6022 is a promising candidate for human stroke therapy.

|||||||||| S-nitrosothiol (N6022) / Alpine, s-nitrosoglutathione (N30-201) / Alpine
Journal: Identification of a Novel Inhibitor of HRV Replication and Inflammation in Airway Epithelial Cells. (Pubmed Central) - Nov 21, 2019
Consistent with this, C3m antiviral effects were not blocked by either NOS inhibition or GSNOR knockdown but appeared to be mediated by reduced ICAM-1 transcription and increased shedding of soluble ICAM-1 protein. Collectively these data show that C3m has novel anti-rhinoviral properties that may synergize with, but are unrelated to, its GSNOR inhibitor activity.

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Journal: S-Nitrosoglutathione Reductase Is Essential for Protecting the Female Heart From Ischemia-Reperfusion Injury. (Pubmed Central) - Sep 28, 2019
Collectively these data show that C3m has novel anti-rhinoviral properties that may synergize with, but are unrelated to, its GSNOR inhibitor activity. These striking findings point to GSNO-R as a critical sex-dependent mediator of myocardial protein SNO and formaldehyde levels and further suggest that different therapeutic strategies may be required to combat ischemic heart disease in males and females.

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Journal: S-Nitrosoglutathione reductase (GSNOR) inhibitor as an immune modulator in experimental autoimmune encephalomyelitis. (Pubmed Central) - Aug 3, 2019
However, neither exogenous GSNO nor N6022 treatment did not cause significant systemic lymphopenic effect as compared to FTY720. Taken together, these data document that optimization of cellular GSNO homeostasis by GSNOR inhibitor (N6022) in NO metabolizing cells attenuates EAE disease via selective inhibition of pro-inflammatory subsets of CD4 cells (T1/T17) while upregulating anti-inflammatory subsets of CD4 cells (T2/Treg) without causing lymphopenic effects and thus offers a potential treatment option for MS/EAE.

|||||||||| S-nitrosothiol (N6022) / Alpine, s-nitrosoglutathione (N30-201) / Alpine
Journal: Effect of the S-nitrosoglutathione reductase inhibitor N6022 on bronchial hyperreactivity in asthma. (Pubmed Central) - Apr 30, 2019
In this early phase exploratory proof of concept trial in asthma, N6022 did not significantly alter methacholine PC FEV1 at 24 h, but did have a treatment effect at 7 days compared to baseline. Further investigation of the efficacy of S-nitrosoglutathione reductase inhibition in a patient population with eosinophilic asthma is warranted.

|||||||||| Herceptin (trastuzumab) / Roche
Journal: Altered S-nitrosothiol homeostasis provides a survival advantage to breast cancer cells in HER2 tumors and reduces their sensitivity to trastuzumab. (Pubmed Central) - Mar 29, 2019
Moreover, gene expression analysis confirmed that high ADH5/GSNOR gene expression was associated with high patient survival rates in HER2 tumors. In conclusion, our data provide evidence of molecular mechanisms contributing to the progression of HER2+ breast cancers and could facilitate the development of therapeutic options to counteract resistance to anti-HER2 therapies.

||||||||||  S-nitrosothiol (N6022) / Laurel Venture Capital
Phase classification:  A Safety Study Evaluating N6022 in Multiple-Ascending Doses in Healthy Subjects (clinicaltrials.gov) -  Jan 20, 2015
P1, N=25, Completed,  Sponsor: N30 Pharmaceuticals, Inc.
In conclusion, our data provide evidence of molecular mechanisms contributing to the progression of HER2+ breast cancers and could facilitate the development of therapeutic options to counteract resistance to anti-HER2 therapies. Phase classification: P1/2 --> P1

||||||||||  S-nitrosothiol (N6022) / Laurel Venture Capital
Trial completion, Trial primary completion date:  SNO-1: Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (clinicaltrials.gov) -  Nov 24, 2014
P1, N=66, Completed,  Sponsor: N30 Pharmaceuticals, Inc.
Phase classification: P1/2 --> P1 Active, not recruiting --> Completed | Trial primary completion date: Oct 2014 --> Apr 2014

||||||||||  S-nitrosothiol (N6022) / Laurel Venture Capital
Enrollment closed:  SNO-1: Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (clinicaltrials.gov) -  May 20, 2014
P1, N=67, Active, not recruiting,  Sponsor: N30 Pharmaceuticals, Inc.
Active, not recruiting --> Completed | Trial primary completion date: Oct 2014 --> Apr 2014 Recruiting --> Active, not recruiting

||||||||||  S-nitrosothiol (N6022) / Laurel Venture Capital
Trial initiation date:  SNO-1: Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (clinicaltrials.gov) -  Jan 27, 2014
P1, N=67, Recruiting,  Sponsor: N30 Pharmaceuticals, Inc.
Recruiting --> Active, not recruiting Initiation date: Jan 2013 --> Feb 2014

||||||||||  S-nitrosothiol (N6022) / Laurel Venture Capital
Enrollment open:  SNO-1: Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (clinicaltrials.gov) -  Jan 30, 2013
P1, N=67, Recruiting,  Sponsor: N30 Pharmaceuticals, Inc.
Initiation date: Jan 2013 --> Feb 2014 Active, not recruiting --> Recruiting

||||||||||  S-nitrosothiol (N6022) / Laurel Venture Capital
New P1 trial:  SNO-1: Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (clinicaltrials.gov) -  Dec 9, 2012
P1, N=67, Recruiting,  Sponsor: N30 Pharmaceuticals, Inc.

||||||||||  S-nitrosothiol (N6022) / Laurel Venture Capital
Trial completion:  Study to Evaluate the Bronchoprotective Effects of a Single Dose of N6022 in Patients With Mild Asthma (clinicaltrials.gov) -  Feb 16, 2012
P1/2, N=14, Completed,  Sponsor: N30 Pharmaceuticals, Inc.
Active, not recruiting --> Recruiting Recruiting --> Completed



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