ArticleBritish journal of pharmacology2014
In vivo effects of the pure aryl hydrocarbon receptor antagonist GNF-351 after oral administration are limited to the gastrointestinal tract.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Aryl hydrocarbon receptor pharmacology-mechanisms, ligands, and therapeutic potential.Pharmacological reviews · 2026Review
- The role of aryl hydrocarbon receptor signalling in COVID-19 pathology and its therapeutic potential.Frontiers in molecular medicine · 2025Review
- Combination screen in multi-cell type tumor spheroids reveals interaction between aryl hydrocarbon receptor antagonists and E1 ubiquitin-activating enzyme inhibitor.SLAS discovery : advancing life sciences R & D · 2024Article
- Alpha-tocopherylquinone-mediated activation of the Aryl Hydrocarbon Receptor regulates the production of inflammation-inducing cytokines and ameliorates intestinal inflammation.Mucosal immunology · 2023Article
- Monoterpenoid aryl hydrocarbon receptor allosteric antagonists protect against ultraviolet skin damage in female mice.Nature communications · 2023Article
- Review
- Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Recent advances in the development of AHR antagonists in immuno-oncology.RSC medicinal chemistry · 2021Review
- Antimigraine Drug Avitriptan Is a Ligand and Agonist of Human Aryl Hydrocarbon Receptor That Induces CYP1A1 in Hepatic and Intestinal Cells.International journal of molecular sciences · 2020Article
- The Aryl Hydrocarbon Receptor: Connecting Immunity to the Microenvironment.Trends in immunology · 2018Review
- The aryl hydrocarbon receptor as a moderator of host-microbiota communication.Current opinion in toxicology · 2017Article
- Metabolic mapping of A3 adenosine receptor agonist MRS5980.Biochemical pharmacology · 2015Article
- Molecular docking to understand the metabolic behavior of GNF-351 by CYP3A4 and its potential drug-drug interaction with ketoconazole.European journal of drug metabolism and pharmacokinetics · 2015Article
- Ganoderic acid B's influence towards the therapeutic window of trifluoperazine (TFP).African health sciences · 2015Article
- LC-MS-based metabolomics: an update.Archives of toxicology · 2014Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
background and purposeGNF-351 is a potent aryl hydrocarbon receptor (AHR) antagonist that inhibits dioxin response element-dependent and independent activities. Here, the absorption, metabolism and in vivo AHR antagonist activity of GNF-351 were investigated. EXPERIMENTAL APPROACH: LC-MS metabolomics was used to analyse GNF-351 metabolism in vitro and in vivo. Recombinant drug-metabolizing enzymes were employed to determine the enzymes involved in GNF-351 metabolism. Analysis of target AHR genes was performed to investigate the inhibitory effects of GNF-351 towards AHR activation. KEY
resultsSeveral phase I metabolites were generated after GNF-351 was incubated with microsomes from human or mouse liver and intestine, including two oxidized GNF-351 and one tri-demethylated GNF-351. Poor absorption from the intestine resulted in no detectable levels of GNF-351 in mouse serum (0-6 h) and urine (24 h) and almost all GNF-351 was found in the faeces after 24 h. Analysis of faeces further revealed all the in vitro phase I metabolites. Novel metabolites were detected, including one di-oxidized GNF-351, two oxidized and tri-demethylated GNF-351, one dehydrogenated product of oxidized GNF-351, and one sulfation product of di-oxidized GNF-351. Cytochromes P450 were demonstrated to be the major enzymes involved in metabolism of GNF-351. After oral administration to mice, GNF-351 readily inhibited β-naphthoflavone-induced AHR activation in ileum and colon, but not that in the liver. CONCLUSION AND IMPLICATIONS: While poor absorption and extensive metabolism after oral administration limited the in vivo effects of the pure AHR antagonist GNF-351 in liver, it could be used to inhibit AHR activation in intestine and colon.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.