Last update 19 Sep 2024

GSNOR

Last update 19 Sep 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

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-891

Target

GSNOR

Mechanism

GSNOR inhibitors

Active Org.

SAJE Pharma LLC

Originator Org.

SAJE Pharma LLC

Active Indication

Crohn Disease [+9]

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

1,135

Literatures (Medical) associated with GSNOR

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 Oct 2024·Pathology - Research and Practice

Impact of alcohol dehydrogenase 3 (ADH3 or ADH1C) genetic variation on head and neck cancer susceptibility: A systematic review, meta-analysis, functional analysis, and trial sequential analysis

Review

Author: Nemati, Houshang ; Kanjorpor, Asal ; Zia, Soha ; Sadeghi, Masoud ; Hatami, Masoud

OBJECTIVESAlcohol drinking is a major risk factor for head and neck cancer (HNC), and this risk may be modified by alcohol dehydrogenase (ADH) genes. The first systematic review and meta-analysis was designed with more studies and added trial sequential analysis and functional analysis for a better understanding of the role of ADH3 polymorphism in HNC patients.METHODSA search was performed across several databases, including PubMed/Medline, Web of Science, Scopus, and Cochrane Library, up to May 5, 2024, without any restrictions to find pertinent studies. The RevMan 5.3 software was used to calculate the effect sizes. These were expressed as the odds ratio (OR) with a 95 % confidence interval.RESULTSTwenty-seven articles were included in the meta-analysis. The frequency of *1/*1, *1/*2, and *2/*2 genotypes in cases with HNC was 47.14 %, 41.06 %, and 11.80 %, respectively, and in controls was 50.56 %, 38.29 %, and 11.15 %, respectively. The pooled OR for the allelic model is 1.11 (p = 0.18), for the homozygous model is 0.95 (p = 0.64), for the heterozygous model is 0.99 (p = 0.90), for the dominant model is 1.11 (p = 0.14), and for the recessive model is 0.98 (p = 0.78). In the Asians, the three models showed an increased significant association. In the cancer subtype subgroup, a protective significant association was found in the pharyngeal cancer subtype.CONCLUSIONSThe current analysis suggests that ADH3 polymorphism may not have a significant impact on the risk of HNC, but the polymorphism had an increased risk in Asians and a protective role in pharyngeal cancers.

01 Oct 2024·Environmental Pollution

Unveiling microbial community structure and metabolic pathway over carbon cloth-titanium nitride-polyaniline biocathode for effective dichloromethane transformation

Article

Author: Yu, Jianming ; Hu, Jun ; Chen, Jianmeng ; Yu, Zhiliang ; Wu, Meng ; Yang, Feng

Chlorinated volatile organic compounds (Cl-VOCs) have dramatically biotoxicity and environmental persistence due to the presence of chlorine atoms, seriously jeopardizing ecological security and human health. Dichloromethane (DCM) as a model pollutant, is widely applied in solvents, extractants and cleaning agents in the pharmaceutical, chemical and food industries. In this study, highly biocompatible and conductive carbon cloth-titanium nitride-polyaniline (CC-TiN-PANI) bioelectrodes were obtained for DCM degradation in microbial electrolysis cell (MEC). The good adhesion of TiN and PANI on the electrode surface was demonstrated. The degradation kinetics were fitted by the Haldane model, compared to the CC bioelectrode (0.8 h^-1), the proportion of maximum degradation rates to half-saturation concentration (V_max/K_m) of CC-TiN (1.4 h^-1) and CC-TiN-PANI (2.2 h^-1) bioelectrodes were enhanced by 1.8 and 2.8 times, respectively. Microbial community structure analysis illuminated that the dominant genera on the biofilm were Alicycliphilus and Hyphomicrobium, and the abundance was enhanced significantly with the modification of TiN and PANI. The dechlorination of DCM to formaldehyde could be catalyzed by DCM dehalogenase (DcmA) or by haloalkane dehalogenase (DhlA). And further oxidized to formate: 1) direct catalyzed by formaldehyde dehydrogenase (FdhA); 2) conjugated with glutathione by S-(hydroxymethyl)-glutathione synthase (Gfa), S-(hydroxymethyl)-glutathione dehydrogenase (FrmA) and S-formyl-glutathione hydrolase (FrmB); 3) conjugation with tetrahydrofolate (H₄F) and/or tetrahydromethanopterin.

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