ArticleBritish journal of pharmacology2010
AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Pooled it
- A tale of two ATPs: biased activation of the P2X3 receptor.Purinergic signalling · 2026Article
- Endogenous forms of ATP-ATPProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The New Wave of Blocking Taste.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- Review
- Visceral Pain in Preterm Infants with Necrotizing Enterocolitis: Underlying Mechanisms and Implications for Treatment.Paediatric drugs · 2025Review
- Finely ordered intracellular domain harbors an allosteric site to modulate physiopathological function of P2X3 receptors.Nature communications · 2024Article
- DT-0111: a novel P2X3 receptor antagonist.Purinergic signalling · 2023Article
- P2X3 receptor antagonism attenuates the progression of heart failure.Nature communications · 2023Article
- The P2X1 receptor as a therapeutic target.Purinergic signalling · 2022Review
- Generation of Human Nociceptor-Enriched Sensory Neurons for the Study of Pain-Related Dysfunctions.Stem cells translational medicine · 2022Article
- Geoffery Burnstock's influence on the evolution of P2X3 receptor pharmacology.Purinergic signalling · 2021Review
- Nanomedicines for Endometriosis: Lessons Learned from Cancer Research.Small (Weinheim an der Bergstrasse, Germany) · 2021Review
- Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing.International journal of molecular sciences · 2021Article
- Pathophysiological Role of Purinergic P2X Receptors in Digestive System Diseases.Frontiers in physiology · 2021Review
- P2X3 Receptor Ligands: Structural Features and Potential Therapeutic Applications.Frontiers in pharmacology · 2021Article
- Voiding Dysfunction in Old Male Rats Associated With Enlarged Prostate and Irregular Afferent-Triggered Reflex Responses.International neurourology journal · 2020Article
- Advances in pharmacotherapy for the treatment of overactive bladder.Current bladder dysfunction reports · 2019Article
- Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation.British journal of pharmacology · 2019Article
- Investigation on 2',3'-ACS medicinal chemistry letters · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposePurinoceptors containing the P2X3 subunit (P2X3 homotrimeric and P2X2/3 heterotrimeric) are members of the P2X family of ion channels gated by ATP and may participate in primary afferent sensitization in a variety of pain-related diseases. The current work describes the in vitro pharmacological characteristics of AF-353, a novel, orally bioavailable, highly potent and selective P2X3/P2X2/3 receptor antagonist. EXPERIMENTAL APPROACH: The antagonistic potencies (pIC(50)) of AF-353 for rat and human P2X3 and human P2X2/3 receptors were determined using methods of radioligand binding, intracellular calcium flux and whole cell voltage-clamp electrophysiology. KEY
resultsThe pIC(50) estimates for these receptors ranged from 7.3 to 8.5, while concentrations 300-fold higher had little or no effect on other P2X channels or on an assortment of receptors, enzymes and transporter proteins. In contrast to A-317491 and TNP-ATP, competition binding and intracellular calcium flux experiments suggested that AF-353 inhibits activation by ATP in a non-competitive fashion. Favourable pharmacokinetic parameters were observed in rat, with good oral bioavailability (%F = 32.9), reasonable half-life (t(1/2) = 1.63 h) and plasma-free fraction (98.2% protein bound). CONCLUSIONS AND IMPLICATIONS: The combination of a favourable pharmacokinetic profile with the antagonist potency and selectivity for P2X3 and P2X2/3 receptors suggests that AF-353 is an excellent in vivo tool compound for study of these channels in animal models and demonstrates the feasibility of identifying and optimizing molecules into potential clinical candidates, and, ultimately, into a novel class of therapeutics for the treatment of pain-related disorders.
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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.