ArticleNature communications2023
Chronic cough relief by allosteric modulation of P2X3 without taste disturbance.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- The role of natural polyphenols in purinergic signaling: from molecular mechanisms to physiological implications.Purinergic signalling · 2026Review
- Cough hypersensitivity risk increases during heatwaves and can be reduced by inhalation of alkaline aerosols of endogenous ions.Scientific reports · 2026Article
- ATP-P2X3 Signaling as a Shared Neural Sensitization Pathway in Endometriosis and Irritable Bowel Syndrome: Mechanisms and Therapeutic Implications.Biomedicines · 2026Review
- Structure of the human P2X3 receptor reveals the basis for subtype-selective inhibition by sivopixant.PLoS biology · 2026Article
- Mechanistic insights into ligand selectivity inActa pharmaceutica Sinica. B · 2026Article
- Investigation of the active compounds and pharmacological mechanisms ofFrontiers in medicine · 2026Article
- Effectiveness of the P2XJournal of asthma and allergy · 2026Article
- Endogenous forms of ATP-ATPProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Understanding interspecies drug response variations between human and rodent P2X7 receptors.Nature communications · 2025Article
- Comparative Analysis of Classic and Novel Antitussives on Cough Suppression in Guinea Pigs.Pharmaceutics · 2025Article
- Heat waves elevate risks of airway hypersensitivity that inhaled endogenous ions reduce.Research square · 2025Article
- Initial Success: Camlipixant in Refractory Chronic Cough.American journal of respiratory and critical care medicine · 2025Article
- Mycobacterial Phenolic Glycolipid Triggers ATP-Mediated Neuronal P2X3 Signaling and Cough.bioRxiv : the preprint server for biology · 2025Article
- Finely ordered intracellular domain harbors an allosteric site to modulate physiopathological function of P2X3 receptors.Nature communications · 2024Article
- Drugs Targeting Cough Receptors: New Therapeutic Options in Refractory or Unexplained Chronic Cough.Drugs · 2024Review
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P2X receptors are cation channels that sense extracellular ATP. Many therapeutic candidates targeting P2X receptors have begun clinical trials or acquired approval for the treatment of refractory chronic cough (RCC) and other disorders. However, the present negative allosteric modulation of P2X receptors is primarily limited to the central pocket or the site below the left flipper domain. Here, we uncover a mechanism of allosteric regulation of P2X3 in the inner pocket of the head domain (IP-HD), and show that the antitussive effects of quercetin and PSFL2915 (our nM-affinity P2X3 inhibitor optimized based on quercetin) on male mice and guinea pigs were achieved by preventing allosteric changes of IP-HD in P2X3. While being therapeutically comparable to the newly licensed P2X3 RCC drug gefapixant, quercetin and PSFL2915 do not have an adverse effect on taste as gefapixant does. Thus, allosteric modulation of P2X3 via IP-HD may be a druggable strategy to alleviate RCC.
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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.