ArticleBioscience reports2014
Novel human D-amino acid oxidase inhibitors stabilize an active-site lid-open conformation.
Article in Bioscience reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Gender-specific effects of sodium benzoate on cognitive improvement in individuals with dementia: a meta-analysis of randomized controlled trials.European archives of psychiatry and clinical neuroscience · 2026Pooled it
- Sulfide regulation and catabolism in health and disease.Signal transduction and targeted therapy · 2025Review
- Therapeutic potential of D-amino acid oxidase inhibitors for cognitive impairment associated with schizophrenia: learnings from luvadaxistat.The international journal of neuropsychopharmacology · 2024Review
- Directly and Indirectly Targeting the Glycine Modulatory Site to Modulate NMDA Receptor Function to Address Unmet Medical Needs of Patients With Schizophrenia.Frontiers in psychiatry · 2021Review
- Synthesis and preliminary evaluation of 4-hydroxy-6-(3-[Bioorganic & medicinal chemistry letters · 2020Article
- Metabolic resistance of the D-peptide RD2 developed for direct elimination of amyloid-β oligomers.Scientific reports · 2019Article
- Synthesis and Biochemical Evaluation of Lid-Open D-Amino Acid Oxidase Inhibitors.Molecules (Basel, Switzerland) · 2019Article
- Gut Microbiota-Based Pharmacokinetics and the Antidepressant Mechanism of Paeoniflorin.Frontiers in pharmacology · 2019Article
- Steric hindrance controls pyridine nucleotide specificity of a flavin-dependent NADH:quinone oxidoreductase.Protein science : a publication of the Protein Society · 2019Article
- Human D-Amino Acid Oxidase: Structure, Function, and Regulation.Frontiers in molecular biosciences · 2018Review
- Modulating D-amino acid oxidase (DAAO) substrate specificity through facilitated solvent access.PloS one · 2018Article
- Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity.Scientific reports · 2017Article
- Assays of D-Amino Acid Oxidase Activity.Frontiers in molecular biosciences · 2017Article
- Competitive Inhibitors Unveil Structure/Function Relationships in Human D-Amino Acid Oxidase.Frontiers in molecular biosciences · 2017Review
- Expression of D-Amino Acid Oxidase (Frontiers in neuroanatomy · 2017Article
- D-Amino acid oxidase inhibitors based on the 5-hydroxy-1,2,4-triazin-6(1H)-one scaffold.Bioorganic & medicinal chemistry letters · 2016Article
- 6-Hydroxy-1,2,4-triazine-3,5(2H,4H)-dione Derivatives as Novel D-Amino Acid Oxidase Inhibitors.Journal of medicinal chemistry · 2015Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The NMDAR (N-methyl-D-aspartate receptor) is a central regulator of synaptic plasticity and learning and memory. hDAAO (human D-amino acid oxidase) indirectly reduces NMDAR activity by degrading the NMDAR co-agonist D-serine. Since NMDAR hypofunction is thought to be a foundational defect in schizophrenia, hDAAO inhibitors have potential as treatments for schizophrenia and other nervous system disorders. Here, we sought to identify novel chemicals that inhibit hDAAO activity. We used computational tools to design a focused, purchasable library of compounds. After screening this library for hDAAO inhibition, we identified the structurally novel compound, 'compound 2' [3-(7-hydroxy-2-oxo-4-phenyl-2H-chromen-6-yl)propanoic acid], which displayed low nM hDAAO inhibitory potency (Ki=7 nM). Although the library was expected to enrich for compounds that were competitive for both D-serine and FAD, compound 2 actually was FAD uncompetitive, much like canonical hDAAO inhibitors such as benzoic acid. Compound 2 and an analog were independently co-crystalized with hDAAO. These compounds stabilized a novel conformation of hDAAO in which the active-site lid was in an open position. These results confirm previous hypotheses regarding active-site lid flexibility of mammalian D-amino acid oxidases and could assist in the design of the next generation of hDAAO inhibitors.
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