ArticleBiochemical pharmacology2016
Structure-based identification and characterisation of structurally novel human P2X7 receptor antagonists.
Article in Biochemical pharmacology, 2016. 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, 29 citations in OpenAlex.
- Effects of New P2X7R Antagonists on Retinal Inflammatory Degenerative Conditions.Inflammation · 2026Article
- Modeling the P2X7 receptor: a comparative analysis of conventional methods and AlphaFold.Frontiers in pharmacology · 2026Article
- Identification of New Human P2X7 Antagonists Using Ligand- and Structure-Based Virtual Screening.Journal of chemical information and modeling · 2025Article
- Dietary resveratrol and β-Hydroxy-β-Methylbutyric acid enhance flavor and modulate intramuscular fat in Tibetan sheep: insights from transcriptomics and lipidomics.Frontiers in veterinary science · 2025Article
- Molecular and metabolic landscape of adenosine triphosphate-induced cell death in cardiovascular disease.World journal of cardiology · 2024Review
- Computational drug development for membrane protein targets.Nature biotechnology · 2024Review
- Leveraging the ATP-P2X7 receptor signalling axis to alleviate traumatic CNS damage and related complications.Medicinal research reviews · 2023Review
- Identification of a novel P2X7 antagonist using structure-based virtual screening.Frontiers in pharmacology · 2022Article
- Structural basis for the functional properties of the P2X7 receptor for extracellular ATP.Purinergic signalling · 2021Review
- Contribution of Val/Ile87 residue in the extracellular domain in agonist-induced current responses of the human and rat P2X7 receptors.Purinergic signalling · 2020Article
- Molecular Modeling Applied to the Discovery of New Lead Compounds for P2 Receptors Based on Natural Sources.Frontiers in pharmacology · 2020Review
- Mapping the Site of Action of Human P2X7 Receptor Antagonists AZ11645373, Brilliant Blue G, KN-62, Calmidazolium, and ZINC58368839 to the Intersubunit Allosteric Pocket.Molecular pharmacology · 2019Article
- Arylboronic acids inhibit P2X7 receptor function and the acute inflammatory response.Journal of bioenergetics and biomembranes · 2019Article
- The Danger Signal Extracellular ATP Is Involved in the Immunomediated Damage of α-Sarcoglycan-Deficient Muscular Dystrophy.The American journal of pathology · 2019Article
- Zidovudine ameliorates pathology in the mouse model of Duchenne muscular dystrophy via P2RX7 purinoceptor antagonism.Acta neuropathologica communications · 2018Article
- Long non‑coding RNA BC168687 small interfering RNA reduces high glucose and high free fatty acid‑induced expression of P2X7 receptors in satellite glial cells.Molecular medicine reports · 2018Article
- P2RX7 Purinoceptor as a Therapeutic Target-The Second Coming?Frontiers in chemistry · 2018Review
- The Molecular Determinants of Small-Molecule Ligand Binding at P2X Receptors.Frontiers in pharmacology · 2018Article
- Unique residues in the ATP gated human P2X7 receptor define a novel allosteric binding pocket for the selective antagonist AZ10606120.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The P2X7 receptor (P2X7R) plays an important role in diverse conditions associated with tissue damage and inflammation, meaning that the human P2X7R (hP2X7R) is an attractive therapeutic target. The crystal structures of the zebrafish P2X4R in the closed and ATP-bound open states provide an unprecedented opportunity for structure-guided identification of new ligands. The present study performed virtual screening of ∼100,000 structurally diverse compounds against the ATP-binding pocket in the hP2X7R. This identified three compounds (C23, C40 and C60) out of 73 top-ranked compounds by testing against hP2X7R-mediated Ca(2+) responses. These compounds were further characterised using Ca(2+) imaging, patch-clamp current recording, YO-PRO-1 uptake and propidium iodide cell death assays. All three compounds inhibited BzATP-induced Ca(2+) responses concentration-dependently with IC50s of 5.1±0.3μM, 4.8±0.8μM and 3.2±0.2μM, respectively. C23 and C40 inhibited BzATP-induced currents in a reversible and concentration-dependent manner, with IC50s of 0.35±0.3μM and 1.2±0.1μM, respectively, but surprisingly C60 did not affect BzATP-induced currents up to 100μM. They suppressed BzATP-induced YO-PRO-1 uptake with IC50s of 1.8±0.9μM, 1.0±0.1μM and 0.8±0.2μM, respectively. Furthermore, these three compounds strongly protected against ATP-induced cell death. Among them, C40 and C60 exhibited strong specificity towards the hP2X7R over the hP2X4R and rP2X3R. In conclusion, our study reports the identification of three novel hP2X7R antagonists with micromolar potency for the first time using a structure-based approach, including the first P2X7R antagonist with preferential inhibition of large pore formation.
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Registered trials
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.