Page last updated: 2024-11-13

af-219

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Gefapixant: a P2X3 receptor antagonist [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID24764487
CHEMBL ID3716057
SCHEMBL ID1493905
MeSH IDM000605061

Synonyms (58)

Synonym
AF9 ,
S6664
HLWURFKMDLAKOD-UHFFFAOYSA-N
5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzenesulfonamide
R1646 ,
SCHEMBL1493905
mk-7264;af-219
CHEMBL3716057
rg1646
5-(2,4-diaminopyrimidin-5-yl)oxy-2-methoxy-4-propan-2-ylbenzenesulfonamide
af219
gtpl9540
lyfnua
gefapixant
5-((2,4-diamino-5-pyrimidinyl)oxy)-4-isopropyl-2-methoxybenzenesulfonamide
1015787-98-0
gefapixant [who-dd]
ro-4926219
af-219
gefapixant [usan]
5-((2,4-diaminopyrimidin-5-yl)oxy)-2-methoxy-4-(propan-2-yl)benzenesulfonamide
ro4926219
5-[(2,4-diaminopyrimidin-5-yl)oxy]-2-methoxy-4-(propan-2-yl)benzenesulfonamide
benzenesulfonamide, 5-((2,4-diamino-5-pyrimidinyl)oxy)-2-methoxy-4-(1-methylethyl)-
gefapixant [inn]
r-1646
6K6L7E3F1L ,
rg-1646
unii-6k6l7e3f1l
c14h19n5o4s
af-219; mk-7264
5-((2,4-diaminopyrimidin-5-yl)oxy)-4-isopropyl-2-methoxybenzenesulfonamide
gefapixant(af-219,mk-7264)
BCP26079
HY-101588
CS-0021727
DB15097
5-[2,4-bis(azanyl)pyrimidin-5-yl]oxy-2-methoxy-4-propan-2-yl-benzenesulfonamide
gefapixant (usan/inn)
EX-A2788
D11349
AMY27911
5-[(2,4-diaminopyrimidin-5-yl)oxy]-2-methoxy-4-(propan-2-yl)benzene-1-sulfonamide
benzenesulfonamide, 5-[(2,4-diamino-5-pyrimidinyl)oxy]-2-methoxy-4-(1-methylethyl)-
ro 4926219
A934898
AKOS037515637
AC-35643
bdbm50533006
5-[(2,4-diamino-5-pyrimidinyl)oxy]-4-isopropyl-2-methoxybenzenesulfonamide
mfcd24539325
SY282739
AS-78086
BM170818
DTXSID401337212
EN300-345539
Z2751991970
5-[(2,4-diaminopyrimidin-5-yl)oxy]-4-isopropyl-2-methoxybenzenesulfonamide

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" The most common adverse events were related to taste disturbance: ageusia (36 [4·9%] of 730 in COUGH-1 and 86 [6·5%] of 1314 in COUGH-2), dysgeusia (118 [16·2%] in COUGH-1 and 277 [21·1%] in COUGH-2), hypergeusia (3 [0·4%] in COUGH-1 and 6 [0×5%] in COUGH-2), hypogeusia (19 [2·6%] in COUGH-1 and 80 [6·1%] in COUGH-2), and taste disorder (28 [3·8%] in COUGH-1 and 46 [3·5%] in COUGH-2)."( Efficacy and safety of gefapixant, a P2X
Birring, SS; Dicpinigaitis, PV; Green, SA; Iskold, B; Li, Q; McGarvey, LP; Morice, AH; Muccino, DR; Nguyen, AM; Pavord, ID; Rosa, C; Schelfhout, J; Smith, JA; Tzontcheva, A, 2022
)
0.72
"Of 36 randomized and treated participants, 28 (100%) receiving gefapixant and 6 (75%) receiving placebo reported ≥ 1 adverse event (AE)."( A Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of 3 Weeks of Orally Administered Gefapixant in Healthy Younger and Older Adults.
Butera, P; Ford, A; Hussain, A; Iwamoto, M; Kitt, M; Nussbaum, J; Smith, S; Stoch, A, 2022
)
0.72
" The primary objective was to evaluate the safety and tolerability of gefapixant, including adverse events (AEs) and discontinuations due to AEs."( A phase 3, randomized, double-blind, clinical study to evaluate the long-term safety and efficacy of gefapixant in Japanese adult participants with refractory or unexplained chronic cough.
Arano, I; Kikuchi, M; La Rosa, C; Muccino, D; Niimi, A; Sagara, H; Sato, A; Shirakawa, M, 2022
)
0.72
" Adverse events were reported by 79 (94%) and 82 (96%) participants in the 15- and 45-mg BID groups, respectively."( A phase 3, randomized, double-blind, clinical study to evaluate the long-term safety and efficacy of gefapixant in Japanese adult participants with refractory or unexplained chronic cough.
Arano, I; Kikuchi, M; La Rosa, C; Muccino, D; Niimi, A; Sagara, H; Sato, A; Shirakawa, M, 2022
)
0.72
" Adverse events were monitored and evaluated."( The Efficacy and Safety of Gefapixant in a Phase 3b Trial of Patients with Recent-Onset Chronic Cough.
Afzal, AS; La Rosa, C; Lu, S; McGarvey, L; Nguyen, AM; Reyfman, PA; Schelfhout, J; Sher, M; Shvarts, YG; Wu, WC; Xu, P, 2023
)
0.91
"This meta-analysis revealed dose-dependent efficacy and adverse effects of gefapixant against chronic cough."( Efficacy and safety of gefapixant for chronic cough: a meta-analysis of randomised controlled trials.
Chen, IW; Chen, JY; Chuang, MH; Ho, CN; Hung, KC; Kang, FC; Lan, KM; Wu, SC; Yew, M, 2023
)
0.91

Pharmacokinetics

ExcerptReferenceRelevance
" However, initial pharmacokinetic (PK) characterization of the P2X3-receptor antagonist gefapixant, developed to treat refractory or unexplained chronic cough, was performed in healthy participants who were predominantly younger adult males."( A Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of 3 Weeks of Orally Administered Gefapixant in Healthy Younger and Older Adults.
Butera, P; Ford, A; Hussain, A; Iwamoto, M; Kitt, M; Nussbaum, J; Smith, S; Stoch, A, 2022
)
0.72
" We report a population pharmacokinetic (PopPK) analysis that characterizes gefapixant pharmacokinetics (PKs), quantifies between- and within-participant variability, and evaluates the impact of intrinsic and extrinsic factors on gefapixant exposure."( Population pharmacokinetic analysis of the P2X3-receptor antagonist gefapixant.
Ait-Oudhia, S; Anton, J; Chawla, A; Gheyas, F; Hussain, A; Kleijn, H; Krishna Ananthula, H; La Rosa, C; Largajolli, A; Nussbaum, J, 2023
)
0.91

Bioavailability

ExcerptReferenceRelevance
" Also, many of the P2R ligands still lack bioavailability due to charged groups or hydrolytic (either enzymatic or chemical) instability."( Medicinal chemistry of adenosine, P2Y and P2X receptors.
Jacobson, KA; Müller, CE, 2016
)
0.43

Dosage Studied

ExcerptRelevanceReference
"In two phase 3, global clinical trials (COUGH-1 and COUGH-2), the P2X3-receptor antagonist gefapixant significantly reduced objective 24-h cough frequency in participants with refractory or unexplained chronic cough (RCC or UCC) at a dosage of 45 mg twice daily (BID), with an acceptable safety profile."( A phase 3, randomized, double-blind, clinical study to evaluate the long-term safety and efficacy of gefapixant in Japanese adult participants with refractory or unexplained chronic cough.
Arano, I; Kikuchi, M; La Rosa, C; Muccino, D; Niimi, A; Sagara, H; Sato, A; Shirakawa, M, 2022
)
0.72
" The gefapixant solution was intraperitoneally injected each time per day for 7 days and the appropriate dosage of gefapixant was determined according to the results of hematoxylin-eosin (HE) staining and myocardial injury biomarkers."( Gefapixant, a Novel P2X3 Antagonist, Protects against Post Myocardial Infarction Cardiac Dysfunction and Remodeling Via Suppressing NLRP3 Inflammasome.
Li, W; Tang, YH; Wei, YZ; Yang, S, 2023
)
0.91
" Patients with mild or moderate RI do not require dosage adjustments; however, for patients with severe RI who are not on dialysis, gefapixant 45 mg once daily is recommended."( Population pharmacokinetic analysis of the P2X3-receptor antagonist gefapixant.
Ait-Oudhia, S; Anton, J; Chawla, A; Gheyas, F; Hussain, A; Kleijn, H; Krishna Ananthula, H; La Rosa, C; Largajolli, A; Nussbaum, J, 2023
)
0.91
" A frequentist random-effects dose-response meta-analysis or pairwise meta-analysis was used for each outcome."( Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough: A Systematic Review and Dose-Response Meta-Analysis.
Chu, DK; Diab, N; Guyatt, GH; Kum, E; O'Byrne, PM; Patel, M; Satia, I; Wahab, M; Zeraatkar, D, 2023
)
0.91
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Pathways (1)

PathwayProteinsCompounds
Purinergic signaling053

Protein Targets (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
P2X purinoceptor 3Rattus norvegicus (Norway rat)Ki0.07080.00980.04030.0708AID1259561
P2X purinoceptor 3Homo sapiens (human)IC50 (µMol)0.04500.00000.20301.5136AID1627253; AID1863330
P2X purinoceptor 3Homo sapiens (human)Ki0.08910.00900.04660.0891AID1259562
P2X purinoceptor 2Homo sapiens (human)Ki0.08910.00900.04660.0891AID1259562
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (27)

Processvia Protein(s)Taxonomy
response to hypoxiaP2X purinoceptor 3Homo sapiens (human)
signal transductionP2X purinoceptor 3Homo sapiens (human)
neuromuscular synaptic transmissionP2X purinoceptor 3Homo sapiens (human)
response to heatP2X purinoceptor 3Homo sapiens (human)
response to coldP2X purinoceptor 3Homo sapiens (human)
response to mechanical stimulusP2X purinoceptor 3Homo sapiens (human)
response to carbohydrateP2X purinoceptor 3Homo sapiens (human)
positive regulation of calcium ion transport into cytosolP2X purinoceptor 3Homo sapiens (human)
urinary bladder smooth muscle contractionP2X purinoceptor 3Homo sapiens (human)
peristalsisP2X purinoceptor 3Homo sapiens (human)
purinergic nucleotide receptor signaling pathwayP2X purinoceptor 3Homo sapiens (human)
regulation of synaptic plasticityP2X purinoceptor 3Homo sapiens (human)
behavioral response to painP2X purinoceptor 3Homo sapiens (human)
positive regulation of calcium-mediated signalingP2X purinoceptor 3Homo sapiens (human)
sensory perception of tasteP2X purinoceptor 3Homo sapiens (human)
establishment of localization in cellP2X purinoceptor 3Homo sapiens (human)
excitatory postsynaptic potentialP2X purinoceptor 3Homo sapiens (human)
protein homotrimerizationP2X purinoceptor 3Homo sapiens (human)
cellular response to ATPP2X purinoceptor 3Homo sapiens (human)
inorganic cation transmembrane transportP2X purinoceptor 3Homo sapiens (human)
calcium ion transmembrane transportP2X purinoceptor 3Homo sapiens (human)
response to hypoxiaP2X purinoceptor 2Homo sapiens (human)
response to ischemiaP2X purinoceptor 2Homo sapiens (human)
detection of hypoxic conditions in blood by carotid body chemoreceptor signalingP2X purinoceptor 2Homo sapiens (human)
neuromuscular synaptic transmissionP2X purinoceptor 2Homo sapiens (human)
neuromuscular junction developmentP2X purinoceptor 2Homo sapiens (human)
sensory perception of soundP2X purinoceptor 2Homo sapiens (human)
response to carbohydrateP2X purinoceptor 2Homo sapiens (human)
positive regulation of calcium ion transport into cytosolP2X purinoceptor 2Homo sapiens (human)
urinary bladder smooth muscle contractionP2X purinoceptor 2Homo sapiens (human)
peristalsisP2X purinoceptor 2Homo sapiens (human)
response to ATPP2X purinoceptor 2Homo sapiens (human)
purinergic nucleotide receptor signaling pathwayP2X purinoceptor 2Homo sapiens (human)
behavioral response to painP2X purinoceptor 2Homo sapiens (human)
skeletal muscle fiber developmentP2X purinoceptor 2Homo sapiens (human)
positive regulation of calcium-mediated signalingP2X purinoceptor 2Homo sapiens (human)
sensory perception of tasteP2X purinoceptor 2Homo sapiens (human)
excitatory postsynaptic potentialP2X purinoceptor 2Homo sapiens (human)
calcium ion transmembrane transportP2X purinoceptor 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (5)

Processvia Protein(s)Taxonomy
purinergic nucleotide receptor activityP2X purinoceptor 3Homo sapiens (human)
extracellularly ATP-gated monoatomic cation channel activityP2X purinoceptor 3Homo sapiens (human)
ATP bindingP2X purinoceptor 3Homo sapiens (human)
purinergic nucleotide receptor activityP2X purinoceptor 2Homo sapiens (human)
extracellularly ATP-gated monoatomic cation channel activityP2X purinoceptor 2Homo sapiens (human)
ATP bindingP2X purinoceptor 2Homo sapiens (human)
ligand-gated monoatomic ion channel activityP2X purinoceptor 2Homo sapiens (human)
identical protein bindingP2X purinoceptor 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (9)

Processvia Protein(s)Taxonomy
plasma membraneP2X purinoceptor 3Homo sapiens (human)
axonP2X purinoceptor 3Homo sapiens (human)
Schaffer collateral - CA1 synapseP2X purinoceptor 3Homo sapiens (human)
hippocampal mossy fiber to CA3 synapseP2X purinoceptor 3Homo sapiens (human)
postsynapseP2X purinoceptor 3Homo sapiens (human)
receptor complexP2X purinoceptor 3Homo sapiens (human)
plasma membraneP2X purinoceptor 3Homo sapiens (human)
plasma membraneP2X purinoceptor 2Homo sapiens (human)
apical plasma membraneP2X purinoceptor 2Homo sapiens (human)
neuronal cell bodyP2X purinoceptor 2Homo sapiens (human)
postsynapseP2X purinoceptor 2Homo sapiens (human)
neuronal dense core vesicleP2X purinoceptor 2Homo sapiens (human)
receptor complexP2X purinoceptor 2Homo sapiens (human)
plasma membraneP2X purinoceptor 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (8)

Assay IDTitleYearJournalArticle
AID1627255Kinetic solubility of the compound in phosphate buffer at pH 7.4 by HPLC analysis2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
New P2X3 receptor antagonists. Part 1: Discovery and optimization of tricyclic compounds.
AID1627258Ratio of efflux to influx in human Caco2 cells2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
New P2X3 receptor antagonists. Part 1: Discovery and optimization of tricyclic compounds.
AID1627257Permeability in vinblastine-treated human Caco2 cells2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
New P2X3 receptor antagonists. Part 1: Discovery and optimization of tricyclic compounds.
AID1627256Intrinsic clearance in human liver microsomes at 1 to 2.5 uM in presence of NADPH2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
New P2X3 receptor antagonists. Part 1: Discovery and optimization of tricyclic compounds.
AID1627253Antagonist activity at human recombinant P2X3 receptor expressed in HEK293-Tet-on cells assessed as alpha,beta-methylene-ATP-stimulated Ca2+ influx by Fluo-4 assay2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
New P2X3 receptor antagonists. Part 1: Discovery and optimization of tricyclic compounds.
AID1863330Antagonist activity at human P2X3R expressed in HEK293 cells assessed as reduction in alphabeta-MeATP-induced intracellular Ca2+ influx pretreated with compound followed by alphabeta-MeATP addition and measured by Fluo-4 dye fluorescence analysis2022European journal of medicinal chemistry, Oct-05, Volume: 240AI-based prediction of new binding site and virtual screening for the discovery of novel P2X3 receptor antagonists.
AID1627259Inhibition of human ERG relative to control2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
New P2X3 receptor antagonists. Part 1: Discovery and optimization of tricyclic compounds.
AID1346621Human P2X3 (P2X receptors)2016Neuropharmacology, 05, Volume: 104Medicinal chemistry of adenosine, P2Y and P2X receptors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (41)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's7 (17.07)24.3611
2020's34 (82.93)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 25.65

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index25.65 (24.57)
Research Supply Index3.97 (2.92)
Research Growth Index5.06 (4.65)
Search Engine Demand Index29.12 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (25.65)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials11 (26.83%)5.53%
Reviews9 (21.95%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other21 (51.22%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]