Gefapixant

Summary

Gefapixant (CHEMBL3716057) is an approved small molecule (ATC R05DB29) targeting P2RX3; indicated across 7 conditions including idiopathic pulmonary fibrosis and osteoarthritis, knee.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: R05DB29
• Targets: 1 (P2RX3)
• Indications: 7 conditions
• Clinical trials: 24
• Chemistry: 353.4 Da · C14H19N5O4S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3716057
Name	Gefapixant
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	24764487
ATC	R05DB29
Molecular formula	C14H19N5O4S
Molecular weight	353.4
InChIKey	HLWURFKMDLAKOD-UHFFFAOYSA-N

SMILES: CC(C)C1=CC(=C(C=C1OC2=CN=C(N=C2N)N)S(=O)(=O)N)OC

IUPAC name: 5-(2,4-diaminopyrimidin-5-yl)oxy-2-methoxy-4-propan-2-ylbenzenesulfonamide

Also known as: Af-219, AF-219, Gefapixant, R-1646, R1646, RG-1646, RG1646, RO-4926219, RO4926219, GEFAPIXANT, Gafepixant

Parent form; salt/anhydrous children: CHEMBL4594278

Patent coverage: 121 distinct patent families (386 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 381 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
P2RX3	P2X3	Antagonist	8.5	1.6%	P56373

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: P2X purinoceptor 3, P2X2/P2X3 heterotrimeric receptor, P2X purinoceptor 3.

Bioactivity

ChEMBL activities: 6 potent at pChembl ≥ 5 of 6 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P2RX3	7.52	IC50	30	nM	CHEMBL_ACT_26004675
P2RX3	7.35	IC50	45	nM	CHEMBL_ACT_19408969
P2RX3	7.35	IC50	45	nM	CHEMBL_ACT_24742998
P49654	7.15	Ki	70.79	nM	CHEMBL_ACT_16361516
P2RX3	7.05	Ki	89.13	nM	CHEMBL_ACT_16361495
P2RX3	6.28	IC50	520	nM	CHEMBL_ACT_26004676

Target pathways

Aggregated over 1 target gene(s): P2RX3.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Elevation of cytosolic Ca2+ levels	1	P2RX3
Platelet homeostasis	1	P2RX3

Dominant GO biological processes

GO term	Targets
response to hypoxia	1
signal transduction	1
neuromuscular synaptic transmission	1
response to heat	1
response to cold	1
response to mechanical stimulus	1
response to carbohydrate	1
positive regulation of calcium ion transport into cytosol	1
urinary bladder smooth muscle contraction	1
peristalsis	1
regulation of synaptic plasticity	1
behavioral response to pain	1
positive regulation of calcium-mediated signaling	1
sensory perception of taste	1
establishment of localization in cell	1

Indications & clinical

Indications

6 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
idiopathic pulmonary fibrosis	2	MONDO:0800504	EFO:0000768
osteoarthritis, knee	2	MONDO:0005416	EFO:0004616
interstitial cystitis	2	MONDO:0018301	EFO:0008507
asthma	2	MONDO:0004979	MONDO:0004979
obstructive sleep apnea syndrome	1	MONDO:0007147	EFO:0003918
kidney failure	1	MONDO:0001106	HP:0000083

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 24.

Phase distribution

Phase	Trials
PHASE2	14
PHASE1	5
PHASE3	4
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03449134	PHASE3	COMPLETED	A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-027)
NCT03696108	PHASE3	COMPLETED	A Study of Gefapixant (MK-7264) in Japanese Adult Participants With Refractory or Unexplained Chronic Cough (MK-7264-038)
NCT04193176	PHASE3	COMPLETED	Efficacy and Safety of Gefapixant (MK-7264) in Women With Chronic Cough and Stress Urinary Incontinence (MK-7264-042)
NCT04193202	PHASE3	COMPLETED	Efficacy and Safety of Gefapixant (MK-7264) in Adult Participants With Recent Onset Chronic Cough (MK-7264-043)
NCT01432730	PHASE2	COMPLETED	A Study to Assess the Efficacy of Gefapixant (MK-7264/AF-219), in Participants With Chronic Cough (MK-7264-006)
NCT01554579	PHASE2	COMPLETED	A Four-Week Multicenter Study Evaluating the Safety and Efficacy of Gefapixant (AF-219/MK-7264) in Subjects With Osteoarthritis of the Knee
NCT01569438	PHASE2	TERMINATED	The Safety and Efficacy of Gefapixant (AF-219/MK-7264) in Female Participants With Interstitial Cystitis /Bladder Pain Syndrome (MK-7264-005)
NCT01993329	PHASE2	COMPLETED	A Study to Evaluate the Effect of Gefapixant (AF-219/MK-7264) on Methacholine Hyper-reactivity in Participants With Asthma (MK-7264-009)
NCT02349425	PHASE2	COMPLETED	A Dose Escalation Study of Gefapixant (AF-219/MK-7264) in Refractory Chronic Cough (MK-7264-010)
NCT02397460	PHASE2	COMPLETED	Effect of Gefapixant (AF-219/MK-7264) on Cough Reflex Sensitivity (MK-7264-015)
NCT02476890	PHASE2	COMPLETED	Effect of Gefapixant (MK-7264/AF-219) on Cough Reflex Sensitivity in Healthy and Chronic Cough Participants (MK-7264-014)
NCT02477709	PHASE2	COMPLETED	A Study to Assess the Tolerability of a Single Dose of Gefapixant (AF-219/MK-7264) in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
NCT02502097	PHASE2	COMPLETED	A Study of Gefapixant (AF-219/MK-7264) in Participants With Idiopathic Pulmonary Fibrosis (IPF) With Persistent Cough (MK-7264-016)
NCT02612610	PHASE2	COMPLETED	A 12-Week Study in Participants With Refractory Chronic Cough (MK-7264-012)
NCT02612623	PHASE2	COMPLETED	An 8-Week Refractory Chronic Cough Study (MK-7264-021)
NCT03482713	PHASE2	COMPLETED	Study of Gefapixant (MK-7264) in Adult Japanese Participants With Unexplained or Refractory Chronic Cough (MK-7264-033)
NCT03569033	PHASE2	TERMINATED	Study of Gefapixant (MK-7264) in Acute Cough for Participants With Induced Viral Upper Respiratory Tract Infection (URTI) (MK-7264-013)
NCT03654326	PHASE2	COMPLETED	A Study to Evaluate the Efficacy and Safety of Gefapixant (MK-7264) in Women With Endometriosis-Related Pain (MK-7264-034)
NCT02229877	PHASE1	COMPLETED	A Study to Assess the Effect of Intragastric pH and Fasting on the Pharmacokinetics of Gefapixant (AF-219/MK-7264)
NCT02492776	PHASE1	COMPLETED	A Multiple-Dose Pharmacokinetics Study of Two Gefapixant (AF-219/MK-7264) Formulations
NCT02790840	PHASE1	COMPLETED	A Multiple-Dose Pharmacokinetics Study of Three Gefapixant (AF-219/MK-7264) Formulations
NCT03108924	PHASE1	COMPLETED	The Pharmacokinetics of Gefapixant (MK-7264) in Participants With Renal Insufficiency (MK-7264-026)
NCT03882801	PHASE1	COMPLETED	Safety and Tolerability of Gefapixant (MK-7264) in Participants With Obstructive Sleep Apnea (MK-7264-039)
NCT05813223	EARLY_PHASE1	RECRUITING	Effect of Gefapixant on Cough-related Brain Activity in Patients With Chronic Cough

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

5 molecules share ≥1 primary target. Top 5 by shared-target count:

Molecule	Source	Status	Shared targets
PROGESTERONE	ChEMBL	Phase 4 (approved)	P2RX3
SURAMIN	ChEMBL	Phase 3	P2RX3
ADENOSINE TRIPHOSPHATE	ChEMBL	Phase 2	P2RX3
ELIAPIXANT	ChEMBL	Phase 2	P2RX3
theophylline	PubChem	Approved	P2RX3