Propafenone

Summary

Propafenone (CHEMBL631) is an approved small-molecule anti-arrhythmia drug (ATC C01BC03) targeting ADRB1, ADRB2, and KCNA5; indicated across 6 conditions including atrial fibrillation and heart failure.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C01BC03
• Targets: 3 (ADRB1, ADRB2, KCNA5)
• Indications: 6 conditions
• Clinical trials: 17
• Chemistry: 341.4 Da · C21H27NO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL631
Name	Propafenone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	4932
ChEBI	CHEBI:63619
ATC	C01BC03
Molecular formula	C21H27NO3
Molecular weight	341.4
InChIKey	JWHAUXFOSRPERK-UHFFFAOYSA-N

SMILES: CCCNCC(COC1=CC=CC=C1C(=O)CCC2=CC=CC=C2)O

IUPAC name: 1-[2-[2-hydroxy-3-(propylamino)propoxy]phenyl]-3-phenylpropan-1-one

ChEBI definition: An aromatic ketone that is 3-(propylamino)propane-1,2-diol in which the hydrogen of the primary hydroxy group is replaced by a 2-(3-phenylpropanoyl)phenyl group. It is a class 1C antiarrhythmic drug with local anesthetic effects, and is used as the hydrochloride salt in the management of supraventricular and ventricular arrhythmias.

Pharmacological roles (ChEBI): anti-arrhythmia drug.

Also known as: GNF-Pf-4594, Propafenon hexal, Propafenona, Propafenone, propafenone, SID26752315, SID90341088, SID104171212, SID26752316, SID50105251, SID50105252, rac-Propafenone

Parent form; salt/anhydrous children: CHEMBL1201063

Patent coverage: 3,770 distinct patent families (12,711 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 12,574 (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
ADRB1	β1-adrenoceptor	Antagonist	6.7	0%	P08588
ADRB2	β2-adrenoceptor	Antagonist	7.44	0.4%	P07550
KCNA5	Kv1.5		4.4	0.2%	P22460

Broader ChEMBL bioactivity targets: 33 (assay-derived). Sample: Survival motor neuron protein, Prelamin-A/C, 5-hydroxytryptamine receptor 2B, Alpha-2C adrenergic receptor, Voltage-dependent L-type calcium channel subunit alpha-1C, Nuclear receptor subfamily 2 group E member 1, Sodium channel protein type 5 subunit alpha, Sulfonylurea receptor 2, Kir6.2, Beta-2 adrenergic receptor, Beta-1 adrenergic receptor.

Bioactivity

ChEMBL activities: 54 potent at pChembl ≥ 5 of 64 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ADRB2	7.44	Ki	36	nM	CHEMBL_ACT_7728662
ADRB2	7.28	IC50	52	nM	CHEMBL_ACT_7728661
HTR2B	7.24	Ki	58	nM	CHEMBL_ACT_7730861
HTR2B	7.04	IC50	92	nM	CHEMBL_ACT_7730860
HTR2A	6.73	Ki	187	nM	CHEMBL_ACT_7730859
HTR2C	6.7	Ki	201	nM	CHEMBL_ACT_7730863
ADRB1	6.69	Ki	205	nM	CHEMBL_ACT_7728660
ABCB1	6.5	EC50	320	nM	CHEMBL_ACT_1019441
ADRB3	6.5	Ki	318	nM	CHEMBL_ACT_7728664
ABCB1	6.48	IC50	331.1	nM	CHEMBL_ACT_10954681
ABCB1	6.48	EC50	331.1	nM	CHEMBL_ACT_13518282
ABCB1	6.48	EC50	329	nM	CHEMBL_ACT_1832763
ADRB1	6.45	IC50	354	nM	CHEMBL_ACT_7728659
ADRB1	6.42	AC50	380	nM	CHEMBL_ACT_25121439
HTR2C	6.42	IC50	384	nM	CHEMBL_ACT_7730862
ADRB3	6.37	IC50	424	nM	CHEMBL_ACT_7728663
KCNH2	6.36	IC50	440	nM	CHEMBL_ACT_15257969
KCNH2	6.18	AC50	660	nM	CHEMBL_ACT_25117343
HTR2A	6.18	IC50	654	nM	CHEMBL_ACT_7730858
KCNH2	6.1	IC50	800	nM	CHEMBL_ACT_1449631
HTR6	6.06	Ki	865	nM	CHEMBL_ACT_7732862
P19327	6.03	Ki	935	nM	CHEMBL_ACT_7730855
SIGMAR1	5.96	Ki	1097	nM	CHEMBL_ACT_7732866
SCN5A	5.92	IC50	1190	nM	CHEMBL_ACT_15257910
P15823	5.85	Ki	1416	nM	CHEMBL_ACT_7728650
SLC6A3	5.83	Ki	1484	nM	CHEMBL_ACT_7728730
P19327	5.79	IC50	1637	nM	CHEMBL_ACT_7730854
O35505	5.75	IC50	1800	nM	CHEMBL_ACT_15257939
O35505	5.75	IC50	1800	nM	CHEMBL_ACT_15373276
SLC6A3	5.73	IC50	1868	nM	CHEMBL_ACT_7728729

Target pathways

Aggregated over 3 target gene(s): ADRB1, ADRB2, KCNA5.

Top Reactome pathways

22 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	2	ADRB1, ADRB2
Signaling by GPCR	2	ADRB1, ADRB2
Class A/1 (Rhodopsin-like receptors)	2	ADRB1, ADRB2
Amine ligand-binding receptors	2	ADRB1, ADRB2
GPCR downstream signalling	2	ADRB1, ADRB2
Adrenoceptors	2	ADRB1, ADRB2
G alpha (s) signalling events	2	ADRB1, ADRB2
GPCR ligand binding	2	ADRB1, ADRB2
Neuronal System	1	KCNA5
Potassium Channels	1	KCNA5
Voltage gated Potassium channels	1	KCNA5
Membrane Trafficking	1	ADRB2
Metabolism of proteins	1	ADRB2
Muscle contraction	1	KCNA5
Phase 3 - rapid repolarisation	1	KCNA5
Cardiac conduction	1	KCNA5
Vesicle-mediated transport	1	ADRB2
Deubiquitination	1	ADRB2
Ub-specific processing proteases	1	ADRB2
Post-translational protein modification	1	ADRB2
Cargo recognition for clathrin-mediated endocytosis	1	ADRB2
Clathrin-mediated endocytosis	1	ADRB2

Dominant GO biological processes

GO term	Targets
diet induced thermogenesis	2
norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure	2
adenylate cyclase-activating G protein-coupled receptor signaling pathway	2
response to cold	2
positive regulation of cardiac muscle cell apoptotic process	2
heat generation	2
negative regulation of multicellular organism growth	2
positive regulation of MAPK cascade	2
brown fat cell differentiation	2
adenylate cyclase-activating adrenergic receptor signaling pathway	2
positive regulation of cold-induced thermogenesis	2
signal transduction	2
G protein-coupled receptor signaling pathway	2
positive regulation of heart rate by epinephrine-norepinephrine	1
positive regulation of the force of heart contraction by epinephrine-norepinephrine	1

Indications & clinical

Indications

6 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
atrial fibrillation	3	MONDO:0004981	EFO:0000275
heart failure	3	MONDO:0005252	EFO:0003144
myocardial infarction	3	MONDO:0005068	EFO:0000612
ventricular fibrillation	3	MONDO:0000190	EFO:0004287

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

Clinical trials

Total trials: 17.

Phase distribution

Phase	Trials
Not specified	7
PHASE4	5
PHASE3	3
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07270848	PHASE4	NOT_YET_RECRUITING	Dronedarone Rhythm Intervention for Early Atrial Fibrillation
NCT02145546	PHASE4	UNKNOWN	Antiarrhythmic Drugs Assessment in Preventing Atrial Fibrillation
NCT03029169	PHASE4	COMPLETED	Propafenone Versus Amiodarone in Septic Shock
NCT03895411	PHASE4	UNKNOWN	Efficacy and Safety of Sotalol in Children With Arrhythmia
NCT05720572	PHASE4	UNKNOWN	Antazoline in Comparison to Propafenone in Pharmacological Cardioversion of Atrial Fibrillation.
NCT00000464	PHASE3	COMPLETED	Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE)
NCT00000556	PHASE3	COMPLETED	Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)
NCT00392106	PHASE3	SUSPENDED	High Intensity Focused Ultrasound (HIFU) Ablation System Study
NCT01956487	PHASE1	COMPLETED	Bioequivalence of RYTHMOL SR® Manufactured at Two Different Sites
NCT03915340	PHASE1	COMPLETED	Bioequivalence Study of Two Formulations of Propafenone 300 mg Film-coated Tablets in Healthy Adult Volunteers After a Single Oral Dose Administration Under Fasting Conditions
NCT00933634	Not specified	COMPLETED	Efficacy and Safety of Electrical Versus Pharmacological Cardioversion in Early Atrial Fibrillation
NCT01991119	Not specified	COMPLETED	Efficacy of Propafenone Versus Dronedarone for the Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation
NCT02294955	Not specified	UNKNOWN	Catheter Ablation Compared With Pharmacological Therapy for Atrial Fibrillation (CAPTAF Trial)
NCT02633774	Not specified	UNKNOWN	Comparison of Brain Perfusion in Rhythm Control and Rate Control of Persistent Atrial Fibrillation
NCT03561935	Not specified	WITHDRAWN	Beta-blocker vs. Ic Antiarrhythmic Drug for PVC
NCT03674658	Not specified	COMPLETED	Propafenone in the Treatment of Atrial Fibrillation
NCT05463614	Not specified	UNKNOWN	Population Pharmacokinetics of Propafenone and Propranolol in Children Patients

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (1) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of DPWG Guideline for propafenone and CYP2D6	DPWG	CYP2D6	yes	yes

PharmGKB also curates 2 clinical and 12 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

248 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Desloratadine	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2
Dihydroergotamine	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2
OLODATEROL	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2
Pramipexole	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2
TAMSULOSIN	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2
ACEBUTOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ALBUTEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ARFORMOTEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ATENOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
BENPERIDOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
BETAXOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
BISOPROLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CARTEOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CARVEDILOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CELIPROLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CLEMASTINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
DARIFENACIN	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
DOBUTAMINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
DOMPERIDONE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
EPINEPHRINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ERGOTAMINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ESMOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
FENOTEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
FORMOTEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
INDACATEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
LABETALOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
LEVOBUNOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
METOPROLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
MONTELUKAST	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
NADOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
NEBIVOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
NOREPINEPHRINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
OXPRENOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PHENYLEPHRINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PIMOZIDE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PINDOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PRACTOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PRENYLAMINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PRIMAQUINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PROPRANOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
RANOLAZINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
RIFAMPIN	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
RIFAXIMIN	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
RITODRINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
SALMETEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
SERTINDOLE	ChEMBL	Phase 4 (approved)	ADRB1, KCNA5
SOTALOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
SUNITINIB	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2