ArticleScientific reports2019
Selective and competitive inhibition of kynurenine aminotransferase 2 by glycyrrhizic acid and its analogues.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Discovery of Personalized Treatment for Immuno-Metabolic Depression-Focus on 11beta Hydroxysteroid Dehydrogenase Type 2 (11betaHSD2) and Toll-like Receptor 4 (TLR4) Inhibition with Enoxolone.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Oxidative phosphorylation is required for cardiomyocyte re-differentiation and long-term fish heart regeneration.Nature cardiovascular research · 2025Article
- Investigation of the Impact of Tryptophan-Metabolizing Enzymes and Kynurenic Acid on Antibody-Mediated Glomerulonephritis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Integrating Molecular Phenotyping into Treatment Algorithms for Advanced Oestrogen Receptor-Positive Breast Cancer.Cancers · 2025Review
- Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Identification of Two Flavonoids as New and Safe Inhibitors of Kynurenine Aminotransferase II via Computational and In Vitro Study.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Review
- The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects.International journal of molecular sciences · 2024Review
- The Complex World of Kynurenic Acid: Reflections on Biological Issues and Therapeutic Strategy.International journal of molecular sciences · 2024Review
- Review
- The Kynurenine Pathway in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Blood Concentrations of Tryptophan and Its Catabolites.Journal of clinical medicine · 2024Review
- The kynurenine pathway of tryptophan metabolism: a neglected therapeutic target of COVID-19 pathophysiology and immunotherapy.Bioscience reports · 2023Article
- In Silico Discovery of Potential Inhibitors Targeting the RNA Binding Loop of ADAR2 and 5-HT2CR from Traditional Chinese Natural Compounds.International journal of molecular sciences · 2023Article
- The association of kynurenine pathway metabolites with symptom severity and clinical features of bipolar disorder: An overview.European psychiatry : the journal of the Association of European Psychiatrists · 2022Review
- Heterocyclic Cathinones as Inhibitors of Kynurenine Aminotransferase II-Design, Synthesis, and Evaluation.Pharmaceuticals (Basel, Switzerland) · 2021Article
- The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives.International journal of molecular sciences · 2021Review
- Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome?Pharmacology & therapeutics · 2020Review
- IDO and Kynurenine Metabolites in Peripheral and CNS Disorders.Frontiers in immunology · 2020Review
- Glycyrrhizic acid mitigates the risk of nicotine addiction and nicotine withdrawal: The modulation of kynurenine aminotransferase II.Journal of advanced pharmaceutical technology & researchArticle
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The enzyme kynurenine aminotransferase (KAT) catalyses the conversion of kynurenine (KYN) to kynurenic acid (KYNA). Although the isozymes KAT1-4 have been identified, KYNA is mainly produced by KAT2 in brain tissues. KNYA is an antagonist of N-methyl-D-aspartate and α-7-nicotinic acetylcholine receptors, and accumulation of KYNA in the brain has been associated with the pathology of schizophrenia. Therefore, KAT2 could be exploited as a therapeutic target for the management of schizophrenia. Although currently available KAT2 inhibitors irreversibly bind to pyridoxal 5'-phosphate (PLP), inhibition via this mechanism may cause adverse side effects because of the presence of other PLP-dependent enzymes. Therefore, we identified novel selective KAT2 inhibitors by screening approximately 13,000 molecules. Among these, glycyrrhizic acid (GL) and its analogues, glycyrrhetinic acid (GA) and carbenoxolone (CBX), were identified as KAT2 inhibitors. These compounds were highly selective for KAT2 and competed with its substrate KYN, but had no effects on the other 3 KAT isozymes. Furthermore, we demonstrated that in complex structures that were predicted in docking calculations, GL, GA and CBX were located on the same surface as the aromatic ring of KYN. These results indicate that GL and its analogues are highly selective and competitive inhibitors of KAT2.
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