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)
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Summary of Clinical Use Click here for help
Gefapixant is being evaluated in clinical trials for indications that are underscored by chronic sensitisation. The most advanced trials are ongoing in patients with chronic refractory/idiopathic cough. A trial in patients with virally-induced acute cough (NCT03569033) was terminated as it was unlikely to meet its study endpoints upon assessment of interim efficacy data. Click here to link to's full list of gefapixant trials.
The following references highlight the clinical potential of ATP antagonism in human diseases: [2,6]. First approval was granted in Japan in 2022, for the treatment of refractory or unexplained chronic cough [4].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01432730 A Study to Assess the Efficacy of Gefapixant (MK-7264/AF-219), in Participants With Chronic Cough (MK-7264-006) Phase 2 Interventional Afferent Pharmaceuticals, Inc. Gefapixant (AF-219) reduces the P2X3 receptor-induced hypersensitisation of airway sensory neurons that can underly chronic cough, and exhibits antitussive efficacy in human trial subjects with refractory chronic cough. 1
NCT02349425 A Dose Escalation Study of Gefapixant (AF-219/MK-7264) in Refractory Chronic Cough Phase 2 Interventional Afferent Pharmaceuticals, Inc. This dose escalation study showed that gefapixant's antitussive efficacy was maintained at lower doses than has been determined previously, and that the lower effective dose improved tolerability. 8
NCT03449147 A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-030) Phase 3 Interventional Merck Sharp & Dohme Corp. The COUGH-2 phase 3 study 5
NCT03449134 A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-027) Phase 3 Interventional Merck Sharp & Dohme LLC The COUGH-1 phase 3 study 5