Dofetilide

Summary

Dofetilide (CHEMBL473) is an approved small-molecule anti-arrhythmia drug (ATC C01BD04) targeting KCNH1 and KCNH2; indicated across 6 conditions including atrial fibrillation and atrial flutter.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C01BD04
• Targets: 2 (KCNH1, KCNH2)
• Indications: 6 conditions
• Clinical trials: 7
• Chemistry: 441.6 Da · C19H27N3O5S2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL473
Name	Dofetilide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	71329
ChEBI	CHEBI:4681
ATC	C01BD04
Molecular formula	C19H27N3O5S2
Molecular weight	441.6
InChIKey	IXTMWRCNAAVVAI-UHFFFAOYSA-N

SMILES: CN(CCC1=CC=C(C=C1)NS(=O)(=O)C)CCOC2=CC=C(C=C2)NS(=O)(=O)C

IUPAC name: N-[4-[2-[2-[4-(methanesulfonamido)phenoxy]ethyl-methylamino]ethyl]phenyl]methanesulfonamide

ChEBI definition: A tertiary amino compound that is N-ethyl-N-methylethanamine substituted by a 4-[(methylsulfonyl)amino]phenoxy and a 4-[(methylsulfonyl)amino]phenyl group at the terminal carbon atoms respectively. It is used as an anti-arrhythmia drug.

Pharmacological roles (ChEBI): anti-arrhythmia drug, potassium channel blocker.

Also known as: Dofetilida, Dofetilide, Tikosyn, UK-68,798, UK-68798, DOFETILIDE, SID26757968, dofetilide, SID144205731, SID170465418, DOFETILIDE CONTROL, DOFETILIDE CONTROLS

Patent coverage: 1,946 distinct patent families (7,465 SureChEMBL compound mentions), from 1 matched compound structure(s). 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
KCNH1	Kv10.1		7.5	0.2%	O95259
KCNH2	Kv11.1	Inhibition	8.19	0.3%	Q12809

Broader ChEMBL bioactivity targets: 7 (assay-derived). Sample: Voltage-gated L-type calcium channel, Muscarinic acetylcholine receptor M2, Acetylcholinesterase, Type-1 angiotensin II receptor, D(3) dopamine receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, Synaptic vesicular amine transporter.

Bioactivity

ChEMBL activities: 30 potent at pChembl ≥ 5 of 34 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
KCNH2	8.39	IC50	4.1	nM	CHEMBL_ACT_12645960
KCNH2	8.3	IC50	5	nM	CHEMBL_ACT_15257958
KCNH2	8.19	Ki	6.4	nM	CHEMBL_ACT_1901318
KCNH2	8.11	Ki	7.7	nM	CHEMBL_ACT_1901343
KCNH2	8.04	IC50	9.2	nM	CHEMBL_ACT_1901350
KCNH2	8	IC50	10	nM	CHEMBL_ACT_1029991
KCNH2	8	IC50	10	nM	CHEMBL_ACT_1523555
KCNH2	8	IC50	10	nM	CHEMBL_ACT_15258078
KCNH2	8	IC50	10	nM	CHEMBL_ACT_2358309
KCNH2	8	IC50	10	nM	CHEMBL_ACT_763438
KCNH2	7.91	IC50	12.3	nM	CHEMBL_ACT_2645530
KCNH2	7.89	IC50	13	nM	CHEMBL_ACT_22987449
KCNH2	7.85	IC50	14	nM	CHEMBL_ACT_25979850
KCNH2	7.85	IC50	14	nM	CHEMBL_ACT_29304831
KCNH2	7.82	IC50	15	nM	CHEMBL_ACT_20638736
KCNH2	7.82	IC50	15	nM	CHEMBL_ACT_320644
KCNH2	7.8	IC50	16	nM	CHEMBL_ACT_29256865
KCNH2	7.59	AC50	25.5	nM	CHEMBL_ACT_25117233
KCNH2	7.52	IC50	30	nM	CHEMBL_ACT_1449518
KCNH2	7.31	IC50	48.98	nM	CHEMBL_ACT_2616690
KCNH2	7.05	IC50	90	nM	CHEMBL_ACT_27107984
KCNH2	6.9	IC50	125.9	nM	CHEMBL_ACT_15258018
KCNH2	6.7	IC50	200	nM	CHEMBL_ACT_16748989
KCNH2	6.2	IC50	631	nM	CHEMBL_ACT_15258050
DRD3	6.11	AC50	780	nM	CHEMBL_ACT_25193112
KCNH2	5.84	IC50	1460	nM	CHEMBL_ACT_22970566
Q01827	5.77	AC50	1700	nM	CHEMBL_ACT_25197341
DRD3	5.47	AC50	3355	nM	CHEMBL_ACT_25194312
CHRM2	5.17	AC50	6726	nM	CHEMBL_ACT_25195521
AGTR1	5.02	AC50	9500	nM	CHEMBL_ACT_25176584

Target pathways

Aggregated over 2 target gene(s): KCNH1, KCNH2.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	2	KCNH1, KCNH2
Potassium Channels	2	KCNH1, KCNH2
Voltage gated Potassium channels	2	KCNH1, KCNH2
Muscle contraction	1	KCNH2
Phase 3 - rapid repolarisation	1	KCNH2
Cardiac conduction	1	KCNH2

Dominant GO biological processes

GO term	Targets
potassium ion transport	2
regulation of membrane potential	2
potassium ion transmembrane transport	2
monoatomic ion transport	2
monoatomic ion transmembrane transport	2
transmembrane transport	2
myoblast fusion	1
regulation of cell population proliferation	1
cellular response to calcium ion	1
regulation of heart rate by hormone	1
positive regulation of DNA-templated transcription	1
potassium ion homeostasis	1
cardiac muscle contraction	1
regulation of membrane repolarization	1
regulation of ventricular cardiac muscle cell membrane repolarization	1

Indications & clinical

Indications

6 indications (4 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	4	MONDO:0004981	EFO:0000275
atrial flutter	4	MONDO:0005310	EFO:0003911
heart failure	3	MONDO:0005252	EFO:0003144

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

Clinical trials

Total trials: 7.

Phase distribution

Phase	Trials
PHASE1	4
PHASE3	1
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00392106	PHASE3	SUSPENDED	High Intensity Focused Ultrasound (HIFU) Ablation System Study
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT01873950	PHASE1	COMPLETED	Study of the Electrocardiographic Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects
NCT02308748	PHASE1	COMPLETED	Ability of Late Sodium or Calcium Current Block to Balance the ECG Effects of Potassium Current Block
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT03070470	PHASE1	COMPLETED	CiPA Phase 1 ECG Biomarker Validation Study
NCT04128878	Not specified	COMPLETED	Improvement in Endothelial Dysfunction After Initiation of Anti-arrhythmic Therapy in Atrial Fibrillation Patients

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 7 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.

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

Molecule	Source	Status	Shared targets
Haloperidol	ChEMBL + PubChem	Phase 4 (approved)	KCNH1, KCNH2
Imipramine	ChEMBL + PubChem	Phase 4 (approved)	KCNH1, KCNH2
Quinidine	ChEMBL + PubChem	Phase 4 (approved)	KCNH1, KCNH2
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
MAVORIXAFOR	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
RELUGOLIX	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
RIOCIGUAT	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
VORAPAXAR	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
ABEMACICLIB	ChEMBL	Phase 4 (approved)	KCNH2
ACENOCOUMAROL	ChEMBL	Phase 4 (approved)	KCNH2
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	KCNH2
ACLIDINIUM BROMIDE	ChEMBL	Phase 4 (approved)	KCNH2
ALBENDAZOLE	ChEMBL	Phase 4 (approved)	KCNH2
ALMOTRIPTAN	ChEMBL	Phase 4 (approved)	KCNH2
ALOSETRON	ChEMBL	Phase 4 (approved)	KCNH2
ALPIDEM	ChEMBL	Phase 4 (approved)	KCNH2
AMBENONIUM	ChEMBL	Phase 4 (approved)	KCNH2
AMCINONIDE	ChEMBL	Phase 4 (approved)	KCNH2
AMIODARONE	ChEMBL	Phase 4 (approved)	KCNH2
AMISULPRIDE	ChEMBL	Phase 4 (approved)	KCNH2
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	KCNH2
AMLODIPINE	ChEMBL	Phase 4 (approved)	KCNH2
AMODIAQUINE	ChEMBL	Phase 4 (approved)	KCNH2
AMOROLFINE	ChEMBL	Phase 4 (approved)	KCNH2
AMOXAPINE	ChEMBL	Phase 4 (approved)	KCNH2
AMSACRINE	ChEMBL	Phase 4 (approved)	KCNH2
ANISOTROPINE	ChEMBL	Phase 4 (approved)	KCNH2
ANTAZOLINE	ChEMBL	Phase 4 (approved)	KCNH2
APOMORPHINE	ChEMBL	Phase 4 (approved)	KCNH2
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	KCNH2
ASCIMINIB	ChEMBL	Phase 4 (approved)	KCNH2
ASENAPINE	ChEMBL	Phase 4 (approved)	KCNH2
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	KCNH2
ATOMOXETINE	ChEMBL	Phase 4 (approved)	KCNH2
ATRACURIUM	ChEMBL	Phase 4 (approved)	KCNH2
AVATROMBOPAG	ChEMBL	Phase 4 (approved)	KCNH2
AZELASTINE	ChEMBL	Phase 4 (approved)	KCNH2
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	KCNH2
BEDAQUILINE	ChEMBL	Phase 4 (approved)	KCNH2
BENFLUOREX	ChEMBL	Phase 4 (approved)	KCNH2
BENOXINATE	ChEMBL	Phase 4 (approved)	KCNH2
BENPERIDOL	ChEMBL	Phase 4 (approved)	KCNH2
BENZPHETAMINE	ChEMBL	Phase 4 (approved)	KCNH2
BENZTROPINE	ChEMBL	Phase 4 (approved)	KCNH2
BENZYDAMINE	ChEMBL	Phase 4 (approved)	KCNH2
BEPRIDIL	ChEMBL	Phase 4 (approved)	KCNH2
BERBERINE	ChEMBL	Phase 4 (approved)	KCNH2
BETRIXABAN	ChEMBL	Phase 4 (approved)	KCNH2
BEXAROTENE	ChEMBL	Phase 4 (approved)	KCNH2
BIFONAZOLE	ChEMBL	Phase 4 (approved)	KCNH2
BIPERIDEN	ChEMBL	Phase 4 (approved)	KCNH2
BITHIONOL	ChEMBL	Phase 4 (approved)	KCNH2
BOSUTINIB	ChEMBL	Phase 4 (approved)	KCNH2
BROMHEXINE	ChEMBL	Phase 4 (approved)	KCNH2
BROMPERIDOL	ChEMBL	Phase 4 (approved)	KCNH2
BUCLIZINE	ChEMBL	Phase 4 (approved)	KCNH2