Flecainide

Summary

Flecainide (CHEMBL652) is an approved small-molecule anti-arrhythmia drug (ATC C01BC04) targeting KCNA1, KCNA2, and KCNA5; indicated across 3 conditions including atrial fibrillation and arrhythmogenic right ventricular cardiomyopathy.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C01BC04
• Targets: 5 (KCNA1, KCNA2, KCNA5…)
• Indications: 3 conditions
• Clinical trials: 24
• Chemistry: 414.34 Da · C17H20F6N2O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL652
Name	Flecainide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3356
ChEBI	CHEBI:75984
ATC	C01BC04
Molecular formula	C17H20F6N2O3
Molecular weight	414.34
InChIKey	DJBNUMBKLMJRSA-UHFFFAOYSA-N

SMILES: C1CCNC(C1)CNC(=O)C2=C(C=CC(=C2)OCC(F)(F)F)OCC(F)(F)F

IUPAC name: N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide

ChEBI definition: A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid with the primary amino group of piperidin-2-ylmethylamine. An antiarrhythmic agent used (in the form of its acetate salt) to prevent and treat tachyarrhythmia (abnormal fast rhythm of the heart).

Pharmacological roles (ChEBI): anti-arrhythmia drug.

Also known as: Flecainida, Flecainide, FLECAINIDE COMPONENT OF THN-102, Flecainide component of thn102, NSC-719273, flecainide, SID26752195, SID104171159, SID124880129, FLECAINIDE, SID170464874, SID144203702

Parent form; salt/anhydrous children: CHEMBL1200822, CHEMBL4591096

Patent coverage: 2,862 distinct patent families (9,582 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 9,396 (98%) 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
KCNA1	Kv1.1		3.7	0%	Q09470
KCNA2	Kv1.2	Pore blocker	3.7	0.7%	P16389
KCNA5	Kv1.5		4	0.2%	P22460
KCNA7	Kv1.7		5.1	0.5%	Q96RP8
KCNC1	Kv3.1		4	1.7%	P48547

Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: A-type voltage-gated potassium channel KCND2, Prelamin-A/C, Voltage-dependent L-type calcium channel subunit alpha-1C, Sodium channel protein type 5 subunit alpha, Voltage-gated L-type calcium channel, Sodium-dependent noradrenaline transporter, Alpha-1A adrenergic receptor, Kappa-type opioid receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, Potassium voltage-gated channel subfamily A member 5.

Bioactivity

ChEMBL activities: 10 potent at pChembl ≥ 5 of 15 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
LMNA	5.9	Potency	1259	nM	CHEMBL_ACT_3663774
KCNH2	5.52	AC50	3000	nM	CHEMBL_ACT_25117494
SCN5A	5.52	AC50	3000	nM	CHEMBL_ACT_25158862
KCNH2	5.41	IC50	3890	nM	CHEMBL_ACT_1060539
KCNH2	5.41	IC50	3890	nM	CHEMBL_ACT_1523703
KCNH2	5.41	IC50	3890	nM	CHEMBL_ACT_2358271
KCNH2	5.41	IC50	3890	nM	CHEMBL_ACT_5218921
SCN5A	5.19	IC50	6500	nM	CHEMBL_ACT_1884750
OPRK1	5.15	AC50	7100	nM	CHEMBL_ACT_25129200
Q63881	5	IC50	10100	nM	CHEMBL_ACT_1884772

Target pathways

Aggregated over 5 target gene(s): KCNA1, KCNA2, KCNA5, KCNA7, KCNC1.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	5	KCNA1, KCNA2, KCNA5, KCNA7, KCNC1
Potassium Channels	5	KCNA1, KCNA2, KCNA5, KCNA7, KCNC1
Voltage gated Potassium channels	5	KCNA1, KCNA2, KCNA5, KCNA7, KCNC1
Muscle contraction	1	KCNA5
Phase 3 - rapid repolarisation	1	KCNA5
Cardiac conduction	1	KCNA5

Dominant GO biological processes

GO term	Targets
action potential	5
protein homooligomerization	5
potassium ion transmembrane transport	5
monoatomic ion transport	5
potassium ion transport	5
monoatomic ion transmembrane transport	5
transmembrane transport	5
neuronal action potential	2
regulation of membrane potential	2
corpus callosum development	2
potassium ion export across plasma membrane	2
optic nerve development	2
regulation of presynaptic membrane potential	2
startle response	1
regulation of muscle contraction	1

Indications & clinical

Indications

3 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
arrhythmogenic right ventricular cardiomyopathy	2	MONDO:0016587	Orphanet:247

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
PHASE4	9
PHASE3	6
Not specified	6
PHASE2	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02347111	PHASE4	RECRUITING	Pharmacogenetic Study of Antiarrhythmic Drugs for Atrial Fibrillation
NCT07270848	PHASE4	NOT_YET_RECRUITING	Dronedarone Rhythm Intervention for Early Atrial Fibrillation
NCT07405671	PHASE4	NOT_YET_RECRUITING	Flecainide Safety in Patients With Coronary Artery Disease and Atrial Fibrillation
NCT00408473	PHASE4	TERMINATED	Comparative Study of Flecainide CR and Placebo in the Early Treatment of Atrial Fibrillation.
NCT00702117	PHASE4	COMPLETED	Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias
NCT01646281	PHASE4	UNKNOWN	Vernakalant Versus Flecainide: Atrial Contractility
NCT03005366	PHASE4	COMPLETED	Predictive Factors to Effectively Terminate Paroxysmal Atrial Fibrillation by Blocking Atrial Selective Ionic Currents
NCT03587558	PHASE4	UNKNOWN	Effects of Carvedilol on Suppressing the Premature Ventricular Complex/Ventricular Tachycardia From Outflow Tract
NCT06142604	PHASE4	WITHDRAWN	Single Dose Flecainide for Early Sinus Rhythm Conversion of Perioperative Atrial Fibrillation After Noncardiac Surgery
NCT05213104	PHASE3	ACTIVE_NOT_RECRUITING	Assessment of Flecainide to Lower the Patent Foramen Ovale Closure Risk of Atrial Arrhythmia or Tachycardia
NCT05631730	PHASE3	RECRUITING	Effect and Safety of Flecainide and Metoprolol Versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse
NCT00000526	PHASE3	COMPLETED	Cardiac Arrhythmia Suppression Trial (CAST)
NCT00000556	PHASE3	COMPLETED	Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)
NCT00392106	PHASE3	SUSPENDED	High Intensity Focused Ultrasound (HIFU) Ablation System Study
NCT02624765	PHASE3	COMPLETED	Prospective Randomized Clinical Trial of Fetal Atrial Flutter & Supraventricular Tachycardia Therapy (FAST RCT)
NCT06205550	PHASE2	NOT_YET_RECRUITING	N-of-1 in ATS and MEPPC
NCT00000504	PHASE2	COMPLETED	Cardiac Arrhythmia Pilot Study (CAPS)
NCT03685149	PHASE2	COMPLETED	Pilot Randomized Trial With Flecainide in ARVC Patients
NCT06949748	Not specified	RECRUITING	Flecainide in Idiopathic Premature Ventricular Contractions and Related Cardiomyopathy
NCT00215774	Not specified	COMPLETED	Flecainide-Short Long Study (Flec-SL)
NCT02110537	Not specified	UNKNOWN	Acupuncture in Persistent Atrial Fibrillation
NCT02294955	Not specified	UNKNOWN	Catheter Ablation Compared With Pharmacological Therapy for Atrial Fibrillation (CAPTAF Trial)
NCT03845010	Not specified	COMPLETED	Elimination of VPB With Ablation Versus Anti-arrhythmic Drug Treatment
NCT04837261	Not specified	COMPLETED	Shortening Duration of Antiarrhythmic Medication for SVT in Infants

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 flecainide and CYP2D6	DPWG	CYP2D6	yes	yes

PharmGKB also curates 4 clinical and 15 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.

17 molecules share ≥1 primary target. Top 17 by shared-target count:

Molecule	Source	Status	Shared targets
DALFAMPRIDINE	ChEMBL + PubChem	Phase 4 (approved)	KCNA1, KCNA5
NIFEDIPINE	ChEMBL + PubChem	Phase 4 (approved)	KCNA1, KCNA5
QUINIDINE	ChEMBL + PubChem	Phase 4 (approved)	KCNA5, KCNA7
Diltiazem	PubChem	Approved	KCNA1, KCNA5
CAPSAICIN	ChEMBL + PubChem	Phase 4 (approved)	KCNA1
Dronedarone	ChEMBL + PubChem	Phase 4 (approved)	KCNA5
SERTINDOLE	ChEMBL	Phase 4 (approved)	KCNA5
VERNAKALANT	ChEMBL	Phase 4 (approved)	KCNA5
CORTISONE	ChEMBL + PubChem	Phase 3 (approved)	KCNA1
BERGAPTEN	ChEMBL	Phase 3	KCNA2
BMS-919373	ChEMBL	Phase 2	KCNA5
TETRYLAMMONIUM	ChEMBL	Phase 2	KCNA1
Amiodarone	PubChem	Approved	KCNA7
Belzutifan	PubChem	Approved	KCNA5
Lidocaine	PubChem	Approved	KCNA5
methoxsalen	PubChem	Approved	KCNA1
Verapamil	PubChem	Approved	KCNA7