Last update 01 Nov 2024

GSNOR

Last update 01 Nov 2024

Basic Info

Synonyms

ADH-3, ADH5, ADHX

+ [12]

Introduction

Catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione (PubMed:8460164). Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate (PubMed:16081420). Class-III ADH is remarkably ineffective in oxidizing ethanol (PubMed:8460164). Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage (PubMed:33355142).

Drugs associated with GSNOR

N-6022

Target

GSNOR

Mechanism

GSNOR inhibitors

Active Org.

Texas Tech University Health Sciences Center

Originator Org.

Nivalis Therapeutics, Inc.

Active Indication

Brain Cancer

Inactive Indication

Asthma [+3]

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SPL-334.1

Target

GSNOR

Mechanism

GSNOR inhibitors

Active Org.

SAJE Pharma LLC

Originator Org.

SAJE Pharma LLC

Active Indication

Asthma [+4]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SPL-850

Target

GSNOR

Mechanism

GSNOR inhibitors

Active Org.

SAJE Pharma LLC

Originator Org.

SAJE Pharma LLC

Active Indication

Crohn Disease [+3]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with GSNOR

NCT04600778 / Unknown statusPhase 2

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Cavosonstat Administered Twice Daily Compared With Placebo for 24 Weeks in Adult Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Brief Summary: The purpose of this study is to to evaluate the efficacy and safety of Cavosonstat administered twice daily compared with Placebo for 24 Weeks in adult subjects with Chronic Obstructive Pulmonary Disease (COPD)
Detailed Description:To investigate the effect of cavosonstat compared with placebo, on the annualized rate of moderate-to-severe acute exacerbations of COPD (AECOPD) over 24 weeks of treatment.
To investigate:
The effect of cavosonstat compared with placebo, on the duration from baseline to first moderate AECOPD event
The effect of cavosonstat compared with placebo, on respiratory function, as assessed by post-bronchodilator percent-predicted forced expiratory volume in one second (ppFEV1)
The effect of cavosonstat compared with placebo on annualized rate of moderate AECOPD over 24 weeks of treatment
The effect of cavosonstat compared with placebo on annualized rate of severe AECOPD over 24 weeks of treatment
The safety and tolerability of cavosonstat compared with placebo
The pharmacokinetics of cavosonstat
Assessment of quality of life

Start Date03 Feb 2021

Sponsor / Collaborator

GSNOR Therapeutics, Inc.

NCT04129931 / Active, not recruitingPhase 2IIT

PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study

The primary objective of this study is to evaluate several interventions given to participants with severe asthma. Interventions are administered in a crossover manner with 16-week treatment periods followed by 8 to 16 week washout.

Start Date19 Dec 2019

Sponsor / Collaborator

The University of North Carolina at Chapel Hill

[+1]

NCT02934139 / CompletedPhase 1

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of N91115 in Healthy Subjects

The present study is designed to assess the safety and tolerability of escalating, multiple ascending doses of Cavosonstat (N91115) in healthy subjects.

Start Date01 Oct 2016

Sponsor / Collaborator

Nivalis Therapeutics, Inc.

100 Clinical Results associated with GSNOR

100 Translational Medicine associated with GSNOR

0 Patents (Medical) associated with GSNOR

1,138

Literatures (Medical) associated with GSNOR

01 Jan 2025·Colloids and Surfaces B: Biointerfaces

Trident-inspired fucoidan-based armor-piercing microcapsule for programmed acute pulmonary embolism treatment

Article

Author: Liu, Ling ; Feng, Feiling ; Li, Weikun ; Qian, Zhicheng ; Liu, Zonghao ; Tan, Xin ; Ge, Liqin ; Yang, Ning

Pulmonary embolism remains the third leading cause of human mortality after malignant tumors and myocardial infarction. Commonly available thrombolytic therapeutic agents suffer from the limitations of very short half-life, inadequate targeting, limited clot penetration, and a propensity for severe bleeding. Inspired by the trident, we developed the armor-piercing microcapsule (MC), fucoidan-urokinase-S-nitrosoglutathione-polydopamine@MC (FUGP@MC), which exhibited a triple combination of photothermal, mechanical and pharmacological thrombolysis for the therapeutic treatment of acute pulmonary embolism (APE). Briefly, the outermost fucoidan layer was utilized for targeting to the APE area. Programmed APE treatment was triggered by near-infrared (NIR) light irradiation. Photothermal thrombolytic therapy was carried out by photothermal conversion of polydopamine. The photothermal conversion broke the S-nitroso bond in S-nitrosoglutathione (GSNO) and produced large amounts of nitric oxide (NO) for mechanical thrombolysis, which subsequently disrupted the interfacial structure of microcapsule to stimulate the release of the urokinase (UK), leading to a triple synergistic thrombolytic effect. The results demonstrated that the embolization residual rate of FUGP@MC (contained ≈ 1452.5 IU/kg UK) group was significantly lower than that of UK (10,000 IU/kg) group (6.35 % VS 16.78 %). Remarkably, FUGP@MC demonstrated a reliable in vivo biosafety proficiency. In summary, trident-inspired armor-piercing microcapsule FUGP@MC reveals a potential avenue for advancing pulmonary embolism therapeutics and promises to be a safer alternative candidate to current drug approaches.

01 Dec 2024·Medical Microbiology and Immunology

The Moraxella catarrhalis AdhC–FghA system is important for formaldehyde detoxification and protection against pulmonary clearance

Article

Author: Othman, Dina ; Elhosseiny, Noha M ; Attia, Ahmed S ; Eltayeb, Wafaa N

AbstractMultidrug-resistant clinical isolates of Moraxella catarrhalis have emerged, increasing the demand for the identification of new treatment and prevention strategies. A thorough understanding of how M. catarrhalis can establish an infection and respond to different stressors encountered in the host is crucial for new drug-target identification. Formaldehyde is a highly cytotoxic compound that can be produced endogenously as a by-product of metabolism and exogenously from environmental sources. Pathways responsible for formaldehyde detoxification are thus essential and are found in all domains of life. The current work investigated the role of the system consisting of the S-hydroxymethyl alcohol dehydrogenase (AdhC), a Zn-dependent class III alcohol dehydrogenase, and the S-formyl glutathione hydrolase (FghA) in the formaldehyde detoxification process in M. catarrhalis. Bioinformatics showed that the components of the system are conserved across the species and are highly similar to those of Streptococcus pneumoniae, which share the same biological niche. Isogenic mutants were constructed to study the function of the system in M. catarrhalis. A single fghA knockout mutant did not confer sensitivity to formaldehyde, while the adhC–fghA double mutant is formaldehyde-sensitive. In addition, both mutants were significantly cleared in a murine pulmonary model of infection as compared to the wild type, demonstrating the system’s importance for this pathogen’s virulence. The respective phenotypes were reversed upon the genetic complementation of the mutants. To date, this is the first study investigating the role of the AdhC–FghA system in formaldehyde detoxification and pathogenesis of M. catarrhalis.

01 Dec 2024·Plant Science

AhGSNOR1 negatively regulates Al-induced programmed cell death by regulating intracellular NO and redox levels

Article

Author: Zhan, Jie ; Pan, Chunliu ; Zhou, Yunyi ; Wang, Aiqin ; Xiao, Dong ; He, Longfei ; Li, Xia ; Jian, Changge

The toxicity of aluminum (Al) in acidic soil inhibits plant development and reduces crop yields. Programmed cell death (PCD) is one of the important mechanisms in the plant response to Al toxicity. However, it is yet unknown if S-nitrosoglutathione reductase (GSNOR) provides Al-PCD. Here, transcription and protein expression of AhGSNOR1 were both induced by Al stress. AhGSNOR1-overexpressing transgenic tobacco plants reduced Al-induced nitric oxide (NO) and S-nitrosothiol accumulation, the inhibitory effect of Al stress on root elongation and the degree of cell death, and enhanced antioxidant enzyme activity to effectively remove hydrogen peroxide. In addition, AhGSNOR1 directly interacted with AhTRXh in vivo. Expression of Trxh3 in AhGSNOR1-overexpressing transgenic plants was significantly upregulated, indicating that AhGSNOR1 positively regulated the transcriptional level of Trxh3. Together, these results suggested that AhGSNOR1 was a negative regulatory factor of Al-induced PCD and improved plant Al-tolerance by modulating intracellular NO and redox homeostasis.

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