ArticleMolecular pharmacology2019
Mapping the Site of Action of Human P2X7 Receptor Antagonists AZ11645373, Brilliant Blue G, KN-62, Calmidazolium, and ZINC58368839 to the Intersubunit Allosteric Pocket.
Article in Molecular pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Purinergic P2X7 Receptor Antagonism Impairs Aerobic Capacity without Detectable Effect on Cardiac Adaptation to Exercise in Mice.ACS pharmacology & translational science · 2026Article
- P2X7 receptor: An emerging therapeutic target in acute myeloid leukemia (Review).International journal of oncology · 2026Review
- A brain-penetrant P2X7R antagonist mitigates Alzheimer's disease pathology.bioRxiv : the preprint server for biology · 2026Article
- Genetic Variations in the P2X7 Receptor: Opportunities and Challenges for Drug Development.International journal of molecular sciences · 2025Review
- A polycyclic scaffold identified by structure-based drug design effectively inhibits the human P2X7 receptor.Nature communications · 2025Article
- On-Cell Saturation Transfer Difference NMR Spectroscopy on Ion Channels: Characterizing Negative Allosteric Modulator Binding Interactions of P2X7.Journal of the American Chemical Society · 2025Article
- Role of the P2X7 receptor in breast cancer progression.Purinergic signalling · 2025Review
- P2X7 receptors: a bibliometric review from 2002 to 2023.Purinergic signalling · 2025Review
- Characterization of the Active Enantiomer and Mapping of the Stereospecific Intermolecular Pattern of a Reference P2X7 Allosteric Antagonist.ACS pharmacology & translational science · 2025Article
- Targeting the P2X7 receptor in cerebrovascular diseases: from molecular mechanisms to preclinical therapeutic potential.Frontiers in pharmacology · 2025Review
- Purinergic Receptor (P2X7R): A Promising Anti-Parkinson's Drug Target.Advanced pharmaceutical bulletin · 2024Review
- Ionotropic purinergic receptor 7 (P2X7) channel structure and pharmacology provides insight regarding non-nucleotide agonism.Channels (Austin, Tex.) · 2024Review
- P2XScience advances · 2024Article
- A current review on P2X7 receptor antagonist patents in the treatment of neuroinflammatory disorders: a patent review on antagonists.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Unlocking the therapeutic potential of P2X7 receptor: a comprehensive review of its role in neurodegenerative disorders.Frontiers in pharmacology · 2024Review
- Synthesis and biological evaluation of carboxamide and quinoline derivatives as P2X7R antagonists.Bioorganic chemistry · 2023Article
- 6-Furopyridine Hexamethylene Amiloride Is a Non-Selective P2X7 Receptor Antagonist.Biomolecules · 2022Article
- Alternatively Spliced Isoforms of the P2X7 Receptor: Structure, Function and Disease Associations.International journal of molecular sciences · 2022Review
- P2X7 receptor: the regulator of glioma tumor development and survival.Purinergic signalling · 2022Article
- Identification of a novel P2X7 antagonist using structure-based virtual screening.Frontiers in pharmacology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The P2X7 receptor is a trimeric ligand-gated ion channel activated by ATP. It is implicated in the cellular response to trauma/disease and considered to have significant therapeutic potential. Using chimeras and point mutants we have mapped the binding site of the P2X7R-selective antagonist AZ11645373 to the known allosteric binding pocket at the interface between two subunits, in proximity to, but separated from the ATP binding site. Our structural model of AZ11645373 binding is consistent with effects of mutations on antagonist sensitivity, and the proposed binding mode explains variation in antagonist sensitivity between the human and rat P2X7 receptors. We have also determined the site of action for the P2X7R-selective antagonists ZINC58368839, brilliant blue G, KN-62, and calmidazolium. The effect of intersubunit allosteric pocket "signature mutants" F88A, T90V, D92A, F103A, and V312A on antagonist sensitivity suggests that ZINC58368839 comprises a binding mode similar to AZ11645373 and other previously characterized antagonists. For the larger antagonists, brilliant blue G, KN-62, and calmidazolium, our data imply an overlapping but distinct binding mode involving the central upper vestibule of the receptor in addition to the intersubunit allosteric pocket. Our work explains the site of action for a series of P2X7R antagonists and establishes "signature mutants" for P2X7R binding-mode characterization.
Indexed as
Identifiers
What OpenQuestion holds
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.