Digoxin

Summary

Digoxin (CHEMBL1751) is an approved small-molecule anti-arrhythmia drug (ATC C01AA05) targeting SLCO4C1; indicated across 41 conditions including atrial fibrillation and cardiovascular disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C01AA05
• Targets: 1 (SLCO4C1)
• Indications: 41 conditions
• Clinical trials: 193
• Chemistry: 780.9 Da · C41H64O14

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1751
Name	Digoxin
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2724385
ChEBI	CHEBI:4551
ATC	C01AA05
Molecular formula	C41H64O14
Molecular weight	780.9
InChIKey	LTMHDMANZUZIPE-PUGKRICDSA-N

SMILES: C[C@@H]1[C@H]([C@H](C[C@@H](O1)O[C@@H]2[C@H](O[C@H](C[C@@H]2O)O[C@@H]3[C@H](O[C@H](C[C@@H]3O)O[C@H]4CC[C@]5([C@@H](C4)CC[C@@H]6[C@@H]5C[C@H]([C@]7([C@@]6(CC[C@@H]7C8=CC(=O)OC8)O)C)O)C)C)C)O)O

IUPAC name: 3-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-[(2R,4S,5S,6R)-5-[(2S,4S,5S,6R)-5-[(2S,4S,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-12,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one

ChEBI definition: A cardenolide glycoside that is digitoxin β-hydroxylated at C-12. A cardiac glycoside extracted from the foxglove plant, Digitalis lanata, it is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation, but the margin between toxic and therapeutic doses is small.

Pharmacological roles (ChEBI): epitope, anti-arrhythmia drug, cardiotonic drug, EC 3.6.3.9 (Na+/K+-transporting ATPase) inhibitor.

Also known as: Digamex, Digoxin, Digoxin pediatric, Digoxina, Digoxine, Digoxinum, Dynamos, Fargoxin, Lanocardin, Lanoxicaps, Lanoxin, Lanoxin pediatric

Patent coverage: 21,965 distinct patent families (67,342 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
SLCO4C1	OATP4C1			0%	Q6ZQN7

Broader ChEMBL bioactivity targets: 24 (assay-derived). Sample: Nuclear receptor ROR-gamma, Prelamin-A/C, ATP-dependent DNA helicase Q1, NPC intracellular cholesterol transporter 1, Ras-related protein Rab-9A, Solute carrier organic anion transporter family member 1B1, Nuclear receptor ROR-gamma, Solute carrier organic anion transporter family member 1B3, Solute carrier organic anion transporter family member 1A4, Sodium/potassium-transporting ATPase subunit alpha-1.

Bioactivity

ChEMBL activities: 41 potent at pChembl ≥ 5 of 48 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P07340	8.26	IC50	5.5	nM	CHEMBL_ACT_18169826
P15917	7.5	Potency	31.6	nM	CHEMBL_ACT_4651787
O35913	7.43	Ki	37	nM	CHEMBL_ACT_11002238
ATP1A2	7.37	Ki	42.8	nM	CHEMBL_ACT_27979808
ATP1B2	7.24	Ki	58	nM	CHEMBL_ACT_27979805
ATP1B1	7.23	Ki	58.7	nM	CHEMBL_ACT_27979802
RORC	6.96	Kd	109	nM	CHEMBL_ACT_14988946
ATP1A1	6.8	IC50	160	nM	CHEMBL_ACT_25465708
TP53	6.8	Potency	158.5	nM	CHEMBL_ACT_4881794
TP53	6.7	Potency	199.5	nM	CHEMBL_ACT_4862541
P06686	6.66	IC50	220	nM	CHEMBL_ACT_15653378
RAB9A	6.65	Potency	223.9	nM	CHEMBL_ACT_3860440
NPC1	6.65	Potency	223.9	nM	CHEMBL_ACT_4712589
NPC1	6.65	Potency	223.9	nM	CHEMBL_ACT_4732300
ATP1A1	6.57	IC50	270	nM	CHEMBL_ACT_18672196
ATP1A1	6.57	Ki	268	nM	CHEMBL_ACT_27979799
RAB9A	6.55	Potency	281.8	nM	CHEMBL_ACT_3846310
ATP1A1	6.54	IC50	290	nM	CHEMBL_ACT_15653372
ATP1A1	6.4	IC50	400	nM	CHEMBL_ACT_109354
PAX8	6.38	AC50	414	nM	CHEMBL_ACT_13106651
P50997	6.3	IC50	500	nM	CHEMBL_ACT_485567
P50997	6.3	IC50	500	nM	CHEMBL_ACT_512600
LMNA	6.25	Potency	562.3	nM	CHEMBL_ACT_3625571
O35913	6.24	Ki	580	nM	CHEMBL_ACT_11002294
P51450	5.85	Potency	1412	nM	CHEMBL_ACT_4806240
P51450	5.85	Potency	1412	nM	CHEMBL_ACT_4814666
P51450	5.8	Potency	1585	nM	CHEMBL_ACT_4955606
RORC	5.75	IC50	1800	nM	CHEMBL_ACT_25505336
STAT3	5.73	IC50	1862	nM	CHEMBL_ACT_4299513
RORC	5.7	IC50	2000	nM	CHEMBL_ACT_12652495

Target pathways

Aggregated over 1 target gene(s): SLCO4C1.

Top Reactome pathways

7 total, by targets touching each:

Pathway	Targets	Genes
Innate Immune System	1	SLCO4C1
Immune System	1	SLCO4C1
Transport of small molecules	1	SLCO4C1
Transport of vitamins, nucleosides, and related molecules	1	SLCO4C1
SLC-mediated transmembrane transport	1	SLCO4C1
Neutrophil degranulation	1	SLCO4C1
Organic anion transport by SLCO transporters	1	SLCO4C1

Dominant GO biological processes

GO term	Targets
monoatomic ion transport	1
spermatogenesis	1
cell differentiation	1
sodium-independent organic anion transport	1
transmembrane transport	1

Indications & clinical

Indications

41 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
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
heart failure	4	MONDO:0005252	EFO:0003144
congestive heart failure	4	MONDO:0005009	EFO:0000373
rheumatoid arthritis	2	MONDO:0008383	EFO:0000685
Kaposi’s sarcoma	2	MONDO:0005055	EFO:0000558
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
breast neoplasm	2	MONDO:0021100	EFO:0003869
metabolic dysfunction-associated steatohepatitis	2	MONDO:0007027	EFO:1001249
actinic keratosis	2	MONDO:0005173	EFO:0002496
malignant pancreatic neoplasm	2	MONDO:0009831	EFO:1000359
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
epilepsy	1	MONDO:0005027	EFO:0000474
hepatitis C virus infection	1	MONDO:0005231	EFO:0003047
HIV infectious disease	1	MONDO:0005109	EFO:0000764
myelodysplastic syndrome	1	MONDO:0018881	EFO:0000198
acute myeloid leukemia	1	MONDO:0018874	EFO:0000222
diabetes mellitus	1	MONDO:0005015	EFO:0000400
neoplasm	1	MONDO:0005070	EFO:0000616
melanoma	1	MONDO:0005105	EFO:0000756
cytomegalovirus infection	1	MONDO:0005132	EFO:0001062
drug dependence	1	MONDO:0005303	EFO:0003890
head and neck cancer	1	MONDO:0005627	EFO:0006859
influenza	1	MONDO:0005812	EFO:0007328
major depressive disorder	1	MONDO:0002009	MONDO:0002009
depressive disorder	1	MONDO:0002050	MONDO:0002050
chronic hepatitis B virus infection	1	MONDO:0005366	EFO:0004239
essential hypertension	1	MONDO:0001134	MONDO:0001134
type 2 diabetes mellitus	1	MONDO:0005148	MONDO:0005148
von Hippel-Lindau disease	1	MONDO:0008667	MONDO:0008667
hereditary angioedema	1	MONDO:0019623	MONDO:0019623
obesity disorder	1	MONDO:0011122	EFO:0001073
chronic obstructive pulmonary disease	1	MONDO:0005002	EFO:0000341

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

Clinical trials

Total trials: 193.

Phase distribution

Phase	Trials
PHASE1	138
Not specified	16
PHASE2	13
PHASE4	12
PHASE3	8
PHASE1/PHASE2	3
EARLY_PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07321509	PHASE4	RECRUITING	Digoxin After Acute Heart Failure
NCT01005602	PHASE4	COMPLETED	Digoxin Dosing in Heart Failure: A Simplified Nomogram Versus Standard Care
NCT01181414	PHASE4	COMPLETED	Spanish Atrial Fibrillation And Resynchronization Study
NCT01699776	PHASE4	COMPLETED	Efficacy Study of Digoxin & Ivabradine to Treat Heart Failure
NCT02046044	PHASE4	UNKNOWN	Digoxin Versus Ivabradine in Heart Failure With Reduced Ejection Fraction
NCT02391337	PHASE4	COMPLETED	Rate Control Therapy Evaluation in Permanent Atrial Fibrillation (RATE-AF)
NCT02489786	PHASE4	COMPLETED	A Prospective Study of Different Digoxin Treatment Regimens in Egyptian Hospital
NCT02743260	PHASE4	COMPLETED	Drug Transporter Interaction Study PHENTRA_2015_KPUK
NCT03136068	PHASE4	COMPLETED	Intrafetal Digoxin as an Adjuvant for Dilation and Evacuation at 20 to 24 Weeks’ Gestation
NCT03783429	PHASE4	COMPLETED	Digoxin Evaluation in Chronic Heart Failure: Investigational Study In Outpatients in the Netherlands
NCT04778787	PHASE4	COMPLETED	Sodium-glucose Cotransporter Type 2 Inhibitors for Acute Cardiorenal Syndrome Prevention
NCT05469204	PHASE4	COMPLETED	Effect of Estrogen Treatment on Drug Metabolism and Transport
NCT03016819	PHASE3	RECRUITING	Phase III Trial of Anlotinib, Catequentinib in Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma, Synovial Sarcoma (APROMISS)
NCT00000556	PHASE3	COMPLETED	Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)
NCT00390546	PHASE3	COMPLETED	Multicenter Study of Antiarrhythmic Medications for Treatment of Infants With Supraventricular Tachycardia
NCT02544815	PHASE3	UNKNOWN	Digoxin Short Term Treatment Assessment Randomized Trial in AHF
NCT02624765	PHASE3	COMPLETED	Prospective Randomized Clinical Trial of Fetal Atrial Flutter & Supraventricular Tachycardia Therapy (FAST RCT)
NCT02797145	PHASE2/PHASE3	UNKNOWN	Intensive Versus Conventional Digoxin Use in Patients With Heart Failure
NCT03718273	PHASE3	COMPLETED	IvaBRAdine blocK of Funny Current for Heart Rate Control in permanEnt Atrial Fibrillation. (BRAKE-AF Study).
NCT04308031	PHASE3	UNKNOWN	Efficacy of Ivabradine in Patient With Both Persistent Atrial Fibrillation and Heart Failure With Reduce Ejection Fraction
NCT05540600	PHASE3	UNKNOWN	Left Atrium Reservoir Function Modulation in Patients With Atrial Fibrillation: Digoxin Versus Beta Blocker
NCT06240403	PHASE2	NOT_YET_RECRUITING	Digoxin and Senolysis in Heart Failure and Diabetes Mellitus
NCT06588699	PHASE2	RECRUITING	Digoxin In NASH (CODIN)
NCT06701812	PHASE2	RECRUITING	Digoxin Medulloblastoma Study
NCT07025850	PHASE1/PHASE2	NOT_YET_RECRUITING	Efficacy Study of Digoxin Combined With Serplulimab and Chemotherapy in First-Line Treatment of MSS Advanced Colorectal Cancer
NCT07047209	PHASE2	ACTIVE_NOT_RECRUITING	Trial of Oral Digoxin in Individuals With Amyotrophic Lateral Sclerosis (ALS)
NCT01162135	PHASE2	COMPLETED	Digoxin for Recurrent Prostate Cancer
NCT01763931	PHASE2	COMPLETED	DIG-HIF-1 Pharmacodynamic Trial in Newly Diagnosed Operable Breast Cancer
NCT01887288	PHASE2	TERMINATED	Capecitabine With Digoxin for Metastatic Breast Cancer
NCT02212639	PHASE2	UNKNOWN	Phase II Multicentric Study of Digoxin Per os in Classic or Endemic Kaposi’ s Sarcoma
NCT02333643	PHASE2	COMPLETED	A Phase 2 Efficacy Study of CLS003 ICVT in Subjects With Cutaneous Warts.
NCT02906800	PHASE1/PHASE2	UNKNOWN	Potentiation of Cisplatin-based Chemotherapy by Digoxin in Advanced Unresectable Head and Neck Cancer Patients
NCT03113071	PHASE1/PHASE2	TERMINATED	Safety and Activity of Digoxin With Decitabine in Adult AML and MDS
NCT04141995	PHASE2	TERMINATED	FOLFIRINOX With Digoxin in Patients With Resectable Pancreatic Cancer
NCT04216693	PHASE2	WITHDRAWN	Digoxin for Patients With Non-alcoholic Steatohepatitis (NASH)
NCT04834557	PHASE2	COMPLETED	Evaluating the Effect of Digoxin and Ursodeoxycholic Acid in Patients With Rheumatoid Arthritis
NCT05014087	PHASE2	TERMINATED	Digoxin In Treatment of Alcohol Associated Hepatitis
NCT03889795	PHASE1	ACTIVE_NOT_RECRUITING	Phase IB Metformin, Digoxin, Simvastatin in Solid Tumors
NCT06601517	PHASE1	NOT_YET_RECRUITING	A Drug-Drug Interaction (DDI) Study of HDM1002 With Repaglinide, Atorvastatin, Digoxin and Rosuvastatin in Healthy Subjects and Overweight Subjects.
NCT06899061	PHASE1	ACTIVE_NOT_RECRUITING	Modular Clinical Pharmacology Study to Evaluate the Drug-drug Interaction Potential and Relative Bioavailability of Saruparib

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

3 molecules share ≥1 primary target. Top 3 by shared-target count:

Molecule	Source	Status	Shared targets
DIGITOXIN	ChEMBL	Phase 4 (approved)	SLCO4C1
LEVOTHYROXINE	ChEMBL	Phase 4 (approved)	SLCO4C1
Liothyronine	PubChem	Approved	SLCO4C1