ArticleScientific reports2015
Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- Protein-protein interaction-mediated signaling networks in ischemic stroke: from molecular mechanisms to therapeutic strategies.Acta pharmacologica Sinica · 2026Review
- Stigmasterol Is Associated with Alterations in nNOS-PSD95/CAPON Signaling and Synaptic Plasticity in a PTSD Model.Antioxidants (Basel, Switzerland) · 2026Article
- Exploring NMDAR pathways in ischemic stroke: implications for neurotoxic and neuroprotective mechanisms and therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Post-stroke effects of IC87201 on neurobehavioral function and brain injuries: A stereological study.IBRO neuroscience reports · 2024Article
- GluN2A and GluN2B N-Methyl-D-Aspartate Receptor (NMDARs) Subunits: Their Roles and Therapeutic Antagonists in Neurological Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Neuronal Nitric Oxide Synthase and Post-Translational Modifications in the Development of Central Nervous System Diseases: Implications and Regulation.Molecules (Basel, Switzerland) · 2023Review
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2022Review
- Nitric Oxide Synthase Inhibitors into the Clinic at Last.Handbook of experimental pharmacology · 2021Article
- Targeting receptor complexes: a new dimension in drug discovery.Nature reviews. Drug discovery · 2020Review
- Modeling rapid and selective capture of nNOS-PSD-95 uncouplers from Sanhuang Xiexin decoction by novel molecularly imprinted polymers based on metal-organic frameworks.RSC advances · 2020Article
- Structure-based optimization of a PDZ-binding motif within a viral peptide stimulates neurite outgrowth.The Journal of biological chemistry · 2019Article
- Neuroinflammation: friend and foe for ischemic stroke.Journal of neuroinflammation · 2019Review
- PDZ Domains as Drug Targets.Advanced therapeutics · 2019Review
- Preso regulates NMDA receptor-mediated excitotoxicity via modulating nitric oxide and calcium responses after traumatic brain injury.Cell death & disease · 2019Article
- Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition.International review of cell and molecular biology · 2019Review
- Targeting NMDA receptors in stroke: new hope in neuroprotection.Molecular brain · 2018Review
- Proteinaceous Regulators and Inhibitors of Protein Tyrosine Phosphatases.Molecules (Basel, Switzerland) · 2018Review
- Regional Specific Modulation of Stress-Induced Neuronal Activation Associated with the PSD95/NOS Interaction Inhibitor ZL006 in the Wistar Kyoto Rat.The international journal of neuropsychopharmacology · 2017Article
Corrections and comments
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Authors and funding
7 authors.
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Abstract
ZL006 and IC87201 have been presented as efficient inhibitors of the nNOS/PSD-95 protein-protein interaction and shown great promise in cellular experiments and animal models of ischemic stroke and pain. Here, we investigate the proposed mechanism of action of ZL006 and IC87201 using biochemical and biophysical methods, such as fluorescence polarization (FP), isothermal titration calorimetry (ITC), and (1)H-(15)N HSQC NMR. Our data show that under the applied in vitro conditions, ZL006 and IC87201 do not interact with the PDZ domains of nNOS or PSD-95, nor inhibit the nNOS-PDZ/PSD-95-PDZ interface by interacting with the β-finger of nNOS-PDZ. Our findings have implications for further medicinal chemistry efforts of ZL006, IC87201 and analogues, and challenge the general and widespread view on their mechanism of action.
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