Digitoxin

Summary

Digitoxin (CHEMBL254219) is an approved small-molecule EC 3.6.3.9 (Na+/K+-transporting ATPase) inhibitor (ATC C01AA04) targeting ATP1A1; indicated across 2 conditions including cardiovascular disorder and cystic fibrosis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C01AA04
• Targets: 1 (ATP1A1)
• Indications: 2 conditions
• Clinical trials: 1
• Chemistry: 764.9 Da · C41H64O13

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL254219
Name	Digitoxin
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	441207
ChEBI	CHEBI:28544
ATC	C01AA04
Molecular formula	C41H64O13
Molecular weight	764.9
InChIKey	WDJUZGPOPHTGOT-XUDUSOBPSA-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]5CC[C@]7([C@@]6(CC[C@@H]7C8=CC(=O)OC8)O)C)C)C)C)O)O

IUPAC name: 3-[(3S,5R,8R,9S,10S,13R,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-14-hydroxy-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 in which the 3β-hydroxy group of digitoxigenin carries a 2,6-dideoxy-β-D-ribo-hexopyranosyl-(1→4)-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1→4)-2,6-dideoxy-β-D-ribo-hexopyranosyl trisaccharide chain.

Pharmacological roles (ChEBI): EC 3.6.3.9 (Na+/K+-transporting ATPase) inhibitor.

Also known as: Cristapurat, CRYSTODIGIN, Crystodigin, Digimerck, Digitalin, crystalline, Digitophyllin, Digitoxin, Digitoxina, Digitoxine, Digitoxinum, Glucodigin

Patent coverage: 4,750 distinct patent families (16,757 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
ATP1A1	sodium/potassium-transporting ATPase subunit α-1	Inhibition	8.1	84.2%	P05023

Broader ChEMBL bioactivity targets: 16 (assay-derived). Sample: Microtubule-associated protein tau, Nuclear receptor ROR-gamma, Prelamin-A/C, NPC intracellular cholesterol transporter 1, Ras-related protein Rab-9A, Solute carrier organic anion transporter family member 4C1, Sodium/potassium-transporting ATPase, Cruzipain, Signal transducer and activator of transcription 3, Cellular tumor antigen p53.

Bioactivity

ChEMBL activities: 20 potent at pChembl ≥ 5 of 22 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ATP1A1	8.1	IC50	8	nM	CHEMBL_ACT_322842
P50997	8.1	IC50	8	nM	CHEMBL_ACT_784290
ATP1A2	7.54	Ki	28.8	nM	CHEMBL_ACT_27979832
ATP1B1	7.53	Ki	29.5	nM	CHEMBL_ACT_27979826
TP53	7.5	Potency	31.6	nM	CHEMBL_ACT_4873701
ATP1B2	7.39	Ki	40.7	nM	CHEMBL_ACT_27979829
ATP1A1	7.05	Ki	89	nM	CHEMBL_ACT_27979823
SLCO4C1	6.92	IC50	120	nM	CHEMBL_ACT_11000844
RAB9A	6.65	Potency	223.9	nM	CHEMBL_ACT_3833633
NPC1	6.6	Potency	251.2	nM	CHEMBL_ACT_4732162
STAT3	6.16	IC50	700	nM	CHEMBL_ACT_4299487
LMNA	6.15	Potency	707.9	nM	CHEMBL_ACT_3640355
LMNA	5.95	Potency	1122	nM	CHEMBL_ACT_3632337
P51450	5.95	Potency	1122	nM	CHEMBL_ACT_4815017
P51450	5.8	Potency	1585	nM	CHEMBL_ACT_4757388
P25779	5.7	Potency	1995	nM	CHEMBL_ACT_3974518
P51450	5.6	Potency	2512	nM	CHEMBL_ACT_4817769
P25779	5.55	Potency	2818	nM	CHEMBL_ACT_3989955
P25779	5.4	Potency	3981	nM	CHEMBL_ACT_3983117
MAPT	5.15	Potency	7080	nM	CHEMBL_ACT_4011581

Target pathways

Aggregated over 1 target gene(s): ATP1A1.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
Disease	1	ATP1A1
Transport of small molecules	1	ATP1A1
Muscle contraction	1	ATP1A1
Cardiac conduction	1	ATP1A1
Ion homeostasis	1	ATP1A1
Infectious disease	1	ATP1A1
Ion transport by P-type ATPases	1	ATP1A1
Potential therapeutics for SARS	1	ATP1A1
SARS-CoV Infections	1	ATP1A1
Viral Infection Pathways	1	ATP1A1
Ion channel transport	1	ATP1A1

Dominant GO biological processes

GO term	Targets
regulation of the force of heart contraction	1
regulation of sodium ion transport	1
intracellular sodium ion homeostasis	1
osmosensory signaling pathway	1
regulation of blood pressure	1
response to xenobiotic stimulus	1
establishment or maintenance of transmembrane electrochemical gradient	1
intracellular potassium ion homeostasis	1
negative regulation of glucocorticoid biosynthetic process	1
sodium ion transmembrane transport	1
sodium ion export across plasma membrane	1
negative regulation of heart contraction	1
positive regulation of heart contraction	1
positive regulation of striated muscle contraction	1
relaxation of cardiac muscle	1

Indications & clinical

Indications

2 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
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
cystic fibrosis	2	MONDO:0009061	MONDO:0009061

Clinical trials

Total trials: 1.

Phase distribution

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00782288	PHASE2	COMPLETED	Phase II Study of Digitoxin to Treat Cystic Fibrosis

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

5 molecules share ≥1 primary target. Top 5 by shared-target count:

Molecule	Source	Status	Shared targets
DIGOXIN	ChEMBL + PubChem	Phase 4 (approved)	ATP1A1
LANSOPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	ATP1A1
OMEPRAZOLE	ChEMBL	Phase 4 (approved)	ATP1A1
ROSTAFUROXIN	ChEMBL	Phase 2	ATP1A1
Pantoprazole	PubChem	Approved	ATP1A1