ArticleMolecular pharmacology2018
Mapping the Allosteric Action of Antagonists A740003 and A438079 Reveals a Role for the Left Flipper in Ligand Sensitivity at P2X7 Receptors.
Article in Molecular pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- P2X7 Signaling in Neuroinflammation: Glial Crosstalk, Redox Integration, and Therapeutic Targeting.Journal of molecular neuroscience : MN · 2026Review
- Effects of New P2X7R Antagonists on Retinal Inflammatory Degenerative Conditions.Inflammation · 2026Article
- Tumor growth inhibitory activity of the P2X7 receptor antagonist AZ10606120 in two cell lines of human glioblastoma.Purinergic signalling · 2026Article
- Differential Effect of P2X7 Receptors on Proliferation and Migration of Human Keratinocytes and Dermal Fibroblasts.International journal of molecular sciences · 2025Article
- P2X7 receptors: a bibliometric review from 2002 to 2023.Purinergic signalling · 2025Review
- Identification of New Human P2X7 Antagonists Using Ligand- and Structure-Based Virtual Screening.Journal of chemical information and modeling · 2025Article
- Characterization of the Active Enantiomer and Mapping of the Stereospecific Intermolecular Pattern of a Reference P2X7 Allosteric Antagonist.ACS pharmacology & translational science · 2025Article
- HSV-1 employs UL56 to antagonize expression and function of cGAMP channels.Cell reports · 2024Article
- Inflammasome modulation with P2X7 inhibitor A438079-loaded dressings for diabetic wound healing.Frontiers in immunology · 2024Article
- Tetracyclic 1,4-Naphthoquinone Thioglucoside Conjugate U-556 Blocks the Purinergic P2X7 Receptor in Macrophages and Exhibits Anti-Inflammatory Activity In Vivo.International journal of molecular sciences · 2023Article
- Skeletal Muscle Atrophy Induced by Diabetes Is Mediated by Non-Selective Channels and Prevented by Boldine.Biomolecules · 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
- The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications.Cancers · 2022Review
- Identification of a novel P2X7 antagonist using structure-based virtual screening.Frontiers in pharmacology · 2022Article
- Fully Flexible Ligand Docking for the P2X7 Receptor Using ROSIE.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Structural basis for the functional properties of the P2X7 receptor for extracellular ATP.Purinergic signalling · 2021Review
- Antagonism of the ATP-gated P2X7 receptor: a potential therapeutic strategy for cancer.Purinergic signalling · 2021Review
- Functional Coupling between the P2XInternational journal of molecular sciences · 2021Article
- The P2XFrontiers in cellular neuroscience · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
P2X7 receptor (P2X7R) activation requires ∼100-fold higher concentrations of ATP than other P2X receptor (P2XR) subtypes. Such high levels are found during cellular stress, and P2X7Rs consequently contribute to a range of pathophysiological conditions. We have used chimeric and mutant P2X7Rs, coupled with molecular modeling, to produce a validated model of the binding mode of the subtype-selective antagonist A438079 at an intersubunit allosteric site. Within the allosteric site large effects on antagonist action were found for point mutants of residues F88A, D92A, F95A, and F103A that were conserved or similar between sensitive/insensitive P2XR subtypes, suggesting that these side-chain interactions were not solely responsible for high-affinity antagonist binding. Antagonist sensitivity was increased with mutations that remove the bulk of side chains around the center of the binding pocket, suggesting that the dimensions of the pocket make a significant contribution to selectivity. Chimeric receptors swapping the left flipper (around the orthosteric site) reduced both ATP and antagonist sensitivity. Point mutations within this region highlighted the contribution of a P2X7R-specific aspartic acid residue (D280) that modeling suggests forms a salt bridge with the lower body region of the receptor. The D280A mutant removing this charge increased ATP potency 15-fold providing a new insight into the low ATP sensitivity of the P2X7R. The ortho- and allosteric binding sites form either side of the
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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.