gefapixant   Click here for help

GtoPdb Ligand ID: 9540

Synonyms: AF-219 | AF219 | Lyfnua® | MK7264 | MK‐7264
Approved drug PDB Ligand Immunopharmacology Ligand
gefapixant is an approved drug (Japan (2022))
Compound class: Synthetic organic
Comment: Gefapixant (MK‐7264, and formerly AF-219) is a P2X3 and P2X2/3 receptor antagonist. Experimental results have shown that gefapixant acts as a reversible allosteric antagonist, that exhibits preferential activity at closed channels.
Studies in rodent models have provided evidence that supports investigation of gefapixant as a novel treatment for chronic sensitisation conditions [7].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 164.82
Molecular weight 353.12
XLogP 0.6
No. Lipinski's rules broken 0
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Canonical SMILES COc1cc(C(C)C)c(cc1S(=O)(=O)N)Oc1cnc(nc1N)N
Isomeric SMILES COc1cc(C(C)C)c(cc1S(=O)(=O)N)Oc1cnc(nc1N)N
InChI InChI=1S/C14H19N5O4S/c1-7(2)8-4-10(22-3)12(24(17,20)21)5-9(8)23-11-6-18-14(16)19-13(11)15/h4-7H,1-3H3,(H2,17,20,21)(H4,15,16,18,19)
1. Abdulqawi R, Dockry R, Holt K, Layton G, McCarthy BG, Ford AP, Smith JA. (2015)
P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study.
Lancet, 385 (9974): 1198-205. [PMID:25467586]
2. Ford AP, Undem BJ. (2013)
The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders.
Front Cell Neurosci, 7: 267. [PMID:24391544]
3. Jacobson KA, Müller CE. (2016)
Medicinal chemistry of adenosine, P2Y and P2X receptors.
Neuropharmacology, 104: 31-49. [PMID:26686393]
4. Markham A. (2022)
Gefapixant: First Approval.
Drugs, 82 (6): 691-695. [PMID:35347635]
5. McGarvey LP, Birring SS, Morice AH, Dicpinigaitis PV, Pavord ID, Schelfhout J, Nguyen AM, Li Q, Tzontcheva A, Iskold B et al.. (2022)
Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials.
Lancet, 399 (10328): 909-923. [PMID:35248186]
6. Ochoa-Cortes F, Liñán-Rico A, Jacobson KA, Christofi FL. (2014)
Potential for developing purinergic drugs for gastrointestinal diseases.
Inflamm Bowel Dis, 20 (7): 1259-87. [PMID:24859298]
7. Richards D, Gever JR, Ford AP, Fountain SJ. (2019)
Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation.
Br J Pharmacol, 176 (13): 2279-2291. [PMID:30927255]
8. Smith JA, Kitt MM, Butera P, Smith SA, Li Y, Xu ZJ, Holt K, Sen S, Sher MR, Ford AP. (2020)
Gefapixant in two randomised dose-escalation studies in chronic cough.
Eur Respir J, 55 (3). [PMID:31949115]