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Compound Detail

CHEMBL473

DOFETILIDE
💊 Approved Drug
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💊 Approved Drug
CN(CCOc1ccc(NS(C)(=O)=O)cc1)CCc1ccc(NS(C)(=O)=O)cc1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL473
Name DOFETILIDE
Phase Approved
Structure Type MOL
InChI Key IXTMWRCNAAVVAI-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Dofetilida Dofetilide Tikosyn UK-68,798 UK-68798
3
Targets
34
Activities
2
Assay Types
27
PK Parameters
20
Publications
5
Known Names
6
Indications
1
Mechanisms

Molecular Properties

441.6
MW (Da)
1.98
ALogP
6
HBA
2
HBD
104.8
PSA (Ų)
0.55
QED
0
Ro5 Violations
11
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1999
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Black Box Warning Natural Product
USAN Stem -ilide
USAN Year 1993

Extended Properties

Molecular Formula C19H27N3O5S2
MW 441.58
Aromatic Rings 2
Heavy Atoms 29
NP-Likeness -1.07

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
HERG blocker BLOCKER Voltage-gated inwardly rectifying potassium channel KCNH2 ✓ ✓

Indications

Arrhythmias, Cardiac Arrhythmias, Cardiac Atrial Fibrillation Atrial Flutter Heart Failure Romano-Ward Syndrome

ATC Classification

C01BD04
dofetilide
Level 1: CARDIOVASCULAR SYSTEM
Level 2: CARDIAC THERAPY

Drug Warnings

Black Box Warning
cardiotoxicity
Country: United States

Activity Summary

IC50 32 meas. best 8.39
Ki 2 meas. best 8.19

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
 IC50 8.39 7.4238 4.1 21
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
 Ki 8.19 8.15 6.4 2
T-cell line
CHEMBL614685
 IC50 6.0 6.0 1000.0 1
Voltage-gated L-type calcium channel
CHEMBL2095229
 IC50 4.57 4.395 26700.0 2

Pharmacokinetic Data

Parameter Value Units Species
CL 6.49 mL.min-1.g-1 Rattus norvegicus
CL 3.73 mL.min-1.g-1 Rattus norvegicus
CL 0.95 mL.min-1.g-1 Canis lupus familiaris
CL 0.25 mL.min-1.g-1 Homo sapiens
CL 13.16 mL.min-1.kg-1 Rattus norvegicus
CL 7.57 mL.min-1.kg-1 Rattus norvegicus
CL 1.93 mL.min-1.kg-1 Canis lupus familiaris
CL 0.51 mL.min-1.kg-1 Homo sapiens
CL 39.5 mL.min-1.kg-1 Rattus norvegicus
CL 22.7 mL.min-1.kg-1 Rattus norvegicus
CL 5.8 mL.min-1.kg-1 Canis lupus familiaris
CL 1.5 mL.min-1.kg-1 Homo sapiens
CL 10.2 mL.min-1.kg-1 Canis lupus familiaris
CL 5.2 mL.min-1.kg-1 Homo sapiens
CL 2.1 mL.min-1.kg-1 Homo sapiens
CL 5.2 mL.min-1.kg-1 Homo sapiens
CL 5.2 mL.min-1.kg-1 Homo sapiens
CL 4.68 uL.min-1.(10^6cells)-1 Homo sapiens
CL 13.18 uL.min-1.(10^6cells)-1 Rattus norvegicus
F 80.0 % Homo sapiens
F 72.0 % Canis lupus familiaris
F 100.0 % Homo sapiens
Fu 0.36 - Homo sapiens
Fu 0.36 - Homo sapiens
MRT 11.0 hr Homo sapiens
T1/2 4.0 hr -
T1/2 8.1 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 4.1 nM 8.39 Displacement of [3H]astemizole from human ERG K+ channel expressed in HEK293 cel... 23473309
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 5.0 nM 8.3 Inhibition of hERG K channel 21300721
Voltage-gated inwardly rectifying potassium channel KCNH2 Ki = 6.4 nM 8.19 Displacement of [3H]dofetilide from hERG expressed in HEK293 cells by SPA 17536794
Voltage-gated inwardly rectifying potassium channel KCNH2 Ki = 7.7 nM 8.11 Binding affinity at hERG expressed in HEK293 cells by fluorescence polarization ... 17536794
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 9.2 nM 8.04 Blockade of hERG expressed in HEK293 cells by whole-cell patch clamp method 17536794
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 10.0 nM 8.0 Inhibitory concentration against potassium channel HERG 15911273
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 10.0 nM 8.0 Inhibition of K+ channel activity in CHO cells expressing HERG Kv11.1 12729675
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 10.0 nM 8.0 Inhibition of rapid delayed inward rectifying potassium current (IKr) measured u... 25087753
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 10.0 nM 8.0 Inhibition of human Potassium channel HERG expressed in mammalian cells 12873512
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 10.0 nM 8.0 Inhibition of human ERG expressed in CHO cells by whole cell patch clamp techniq... 18448342
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 12.3 nM 7.91 Inhibition of human ERG in MCF7 cells 19110341
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 13.0 nM 7.89 Inhibition of human ERG stably expressed in HEK293 cells by whole-cell manual pa... 32927218
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 14.0 nM 7.85 Inhibition of hERG transfected in HEK293 cells by patch clamp assay 38551814
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 15.0 nM 7.82 K+ channel blocking activity in human embryonic kidney cells expressing HERG Kv1... 12190308
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 15.0 nM 7.82 Inhibition of human ERG stably expressed in HEK293 cells 32453591
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 30.0 nM 7.52 Inhibitory concentration against IKr potassium channel 15324906
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 48.98 nM 7.31 Inhibition of human ERG channel in HEK293 cells by voltage-clamp method 18262683
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 90.0 nM 7.05 hERG Inhibition Activity Assay: 1. CHO-hERG cells which have been incubated over... -
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 125.89 nM 6.9 Inhibition of rapid delayed inward rectifying potassium current (IKr) in Chinese... 25087753
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 200.0 nM 6.7 Inhibition of human ERG 27709945

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL4295262 Unchecked 62
1956040 10.1021/jm00115a010 Canis familiaris 30
11311053 10.1021/jm000407e ADMET 24
1542097 10.1021/jm00082a011 Canis familiaris 17
2319561 10.1021/jm00166a011 Cavia porcellus 14
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
20070106 10.1021/jm901371v Homo sapiens 8
37468498 10.1038/s41467-023-40064-9 Alpha-1A adrenergic receptor 6
- 10.6019/CHEMBL3301361 ADMET 5
17536794 10.1021/jm0700565 Voltage-gated inwardly rectifying potassium channel KCNH2 5
- 10.6019/CHEMBL3301361 No relevant target 5
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2B 4
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 1A 4
12086482 10.1021/jm010574u Cavia porcellus 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
37468498 10.1038/s41467-023-40064-9 Alpha-2A adrenergic receptor 4
11012018 10.1016/s0960-894x(00)00412-1 Unchecked 4
9990462 10.1016/s0960-894x(98)00689-1 Cavia porcellus 4
37468498 10.1038/s41467-023-40064-9 Muscarinic acetylcholine receptor M2 4
18426954 10.1124/dmd.108.020479 ADMET 4

Data from ChEMBL 36 via Core Engine