ArticleBioorganic & medicinal chemistry letters2015
Docking of competitive inhibitors to the P2X7 receptor family reveals key differences responsible for changes in response between rat and human.
Article in Bioorganic & medicinal chemistry letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- P2X7 receptor as a key player in pathological pain: insights into Neuropathic, inflammatory, and cancer pain.Frontiers in pharmacology · 2025Pooled it
- Modeling the P2X7 receptor: a comparative analysis of conventional methods and AlphaFold.Frontiers in pharmacology · 2026Article
- Genetic Variations in the P2X7 Receptor: Opportunities and Challenges for Drug Development.International journal of molecular sciences · 2025Review
- Characterization of the Active Enantiomer and Mapping of the Stereospecific Intermolecular Pattern of a Reference P2X7 Allosteric Antagonist.ACS pharmacology & translational science · 2025Article
- Emerging roles of the P2X7 receptor in cancer pain.Purinergic signalling · 2023Review
- An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential.Cancer cell international · 2023Review
- Spotlight on P2X7 Receptor PET Imaging: A Bright Target or a Failing Star?International journal of molecular sciences · 2023Review
- 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
- P2X7 in Cancer: From Molecular Mechanisms to Therapeutics.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
- P2X7 ionotropic receptor is functionally expressed in rabbit articular chondrocytes and mediates extracellular ATP cytotoxicity.Purinergic signalling · 2018Article
- The Molecular Determinants of Small-Molecule Ligand Binding at P2X Receptors.Frontiers in pharmacology · 2018Article
- Conformational changes during human P2X7 receptor activation examined by structural modelling and cysteine-based cross-linking studies.Purinergic signalling · 2017Article
- Structure-based identification and characterisation of structurally novel human P2X7 receptor antagonists.Biochemical pharmacology · 2016Article
- LncRNA NONRATT021972 involved the pathophysiologic processes mediated by P2X7 receptors in stellate ganglia after myocardial ischemic injury.Purinergic signalling · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The P2X7 receptor is a calcium permeable cationic channel activated by extracellular ATP, playing a role in chronic pain, osteoporosis and arthritis. A number of potential lead compounds are inactive against the rat isoform, despite good activity against the human homologue, making animal model studies problematic. Here we have produced P2X7 models and docked three structurally distinct inhibitors using in silico approaches and show they have a similar mode of binding in which Phe95 plays a key role by forming pi-stacking interactions. Importantly this residue is replaced by Leu in the rat P2X7 receptor resulting in a significantly reduced binding affinity. This work provides new insights into binding of P2X7 inhibitors and shows the structural difference in human and rat P2X7 receptors which results in a difference in affinity. Such information is useful both for the rational design of inhibitors based on these scaffolds and also the way in which these compounds are tested in animal models.
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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.