Hmdb loader
Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2022-03-07 02:51:59 UTC
HMDB IDHMDB0015468
Secondary Accession Numbers
  • HMDB15468
Metabolite Identification
Common NameDigitoxin
DescriptionDigitoxin is a cardenolide glycoside in which the 3beta-hydroxy group of digitoxigenin carries a 2,6-dideoxy-beta-D-ribo-hexopyranosyl-(1->4)-2,6-dideoxy-beta-D-ribo-hexopyranosyl-(1->4)-2,6-dideoxy-beta-D-ribo-hexopyranosyl trisaccharide chain. It has a role as an EC 3.6.3.9 (Na(+)/K(+)-transporting ATPase) inhibitor. It derives from a digitoxigenin. It is a conjugate acid of a digitoxin(1-). Digitoxin appears as odorless white or pale buff microcrystalline powder. It is a cardiac glycoside sometimes used in place of digoxin. It has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting. Digitoxin inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Digitoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.
Structure
Data?1582753300
Synonyms
ValueSource
CrystodiginChEBI
DigitoxosideChEBI
DigitoksinHMDB
DigitoxinumHMDB
Bürger, digitoxinHMDB
Didier, digitoxinHMDB
Digitoxin awdHMDB
Digitoxin didierHMDB
DigimedHMDB
DigophtonHMDB
Nativelle, digitalineHMDB
DigimerckHMDB
Digitoxin bürgerHMDB
AWD, digitoxinHMDB
CoramedanHMDB
Digitaline nativelleHMDB
Digitoxin philoHMDB
Digitoxin-philoHMDB
Chemical FormulaC41H64O13
Average Molecular Weight764.9391
Monoisotopic Molecular Weight764.434692134
IUPAC Name4-[(1S,2S,5S,7R,10R,11S,14R,15R)-5-{[(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}-11-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-14-yl]-2,5-dihydrofuran-2-one
Traditional Name4-[(1S,2S,5S,7R,10R,11S,14R,15R)-5-{[(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}-11-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-14-yl]-5H-furan-2-one
CAS Registry Number71-63-6
SMILES
[H][C@]12CC[C@]3([H])[C@]([H])(CC[C@]4(C)[C@H](CC[C@]34O)C3=CC(=O)OC3)[C@@]1(C)CC[C@@H](C2)O[C@H]1C[C@H](O)[C@H](O[C@H]2C[C@H](O)[C@H](O[C@H]3C[C@H](O)[C@H](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O1
InChI Identifier
InChI=1S/C41H64O13/c1-20-36(46)29(42)16-34(49-20)53-38-22(3)51-35(18-31(38)44)54-37-21(2)50-33(17-30(37)43)52-25-8-11-39(4)24(15-25)6-7-28-27(39)9-12-40(5)26(10-13-41(28,40)47)23-14-32(45)48-19-23/h14,20-22,24-31,33-38,42-44,46-47H,6-13,15-19H2,1-5H3/t20-,21-,22-,24-,25+,26-,27+,28-,29+,30+,31+,33+,34+,35+,36-,37-,38-,39+,40-,41+/m1/s1
InChI KeyWDJUZGPOPHTGOT-XUDUSOBPSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as cardenolide glycosides and derivatives. Cardenolide glycosides and derivatives are compounds containing a carbohydrate glycosidically bound to the cardenolide moiety.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassSteroid lactones
Direct ParentCardenolide glycosides and derivatives
Alternative Parents
Substituents
  • Cardanolide-glycoside
  • Steroidal glycoside
  • Oligosaccharide
  • 14-hydroxysteroid
  • Hydroxysteroid
  • Glycosyl compound
  • O-glycosyl compound
  • 2-furanone
  • Oxane
  • Cyclic alcohol
  • Dihydrofuran
  • Alpha,beta-unsaturated carboxylic ester
  • Enoate ester
  • Tertiary alcohol
  • Lactone
  • Carboxylic acid ester
  • Secondary alcohol
  • Monocarboxylic acid or derivatives
  • Organoheterocyclic compound
  • Oxacycle
  • Acetal
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Alcohol
  • Organic oxide
  • Organic oxygen compound
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
Process
Role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point255.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.029 g/LNot Available
LogP1.85SANGSTER (1993)
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.029 g/LALOGPS
logP2.33ALOGPS
logP3.6ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)7.18ChemAxon
pKa (Strongest Basic)0.24ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area182.83 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity191.72 m³·mol⁻¹ChemAxon
Polarizability83.54 ųChemAxon
Number of Rings8ChemAxon
BioavailabilityNoChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M-2H]-296.91530932474
DeepCCS[M+Na]+270.71230932474
AllCCS[M+H]+267.332859911
AllCCS[M+H-H2O]+267.432859911
AllCCS[M+NH4]+267.232859911
AllCCS[M+Na]+267.232859911
AllCCS[M-H]-233.832859911
AllCCS[M+Na-2H]-239.032859911
AllCCS[M+HCOO]-244.832859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
Digitoxin[H][C@]12CC[C@]3([H])[C@]([H])(CC[C@]4(C)[C@H](CC[C@]34O)C3=CC(=O)OC3)[C@@]1(C)CC[C@@H](C2)O[C@H]1C[C@H](O)[C@H](O[C@H]2C[C@H](O)[C@H](O[C@H]3C[C@H](O)[C@H](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O14367.0Standard polar33892256
Digitoxin[H][C@]12CC[C@]3([H])[C@]([H])(CC[C@]4(C)[C@H](CC[C@]34O)C3=CC(=O)OC3)[C@@]1(C)CC[C@@H](C2)O[C@H]1C[C@H](O)[C@H](O[C@H]2C[C@H](O)[C@H](O[C@H]3C[C@H](O)[C@H](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O15671.7Standard non polar33892256
Digitoxin[H][C@]12CC[C@]3([H])[C@]([H])(CC[C@]4(C)[C@H](CC[C@]34O)C3=CC(=O)OC3)[C@@]1(C)CC[C@@H](C2)O[C@H]1C[C@H](O)[C@H](O[C@H]2C[C@H](O)[C@H](O[C@H]3C[C@H](O)[C@H](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O16090.5Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Digitoxin GC-MS (TMS_1_1) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Digitoxin GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Digitoxin GC-MS (TMS_1_3) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Digitoxin GC-MS (TMS_1_4) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Digitoxin GC-MS (TMS_1_5) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Digitoxin GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Digitoxin GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Digitoxin GC-MS (TBDMS_1_3) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Digitoxin GC-MS (TBDMS_1_4) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Digitoxin GC-MS (TBDMS_1_5) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
MSMass Spectrum (Electron Ionization)splash10-052g-9620000000-5ddc0df4702d2f0b85812014-09-20Not AvailableView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Digitoxin 10V, Positive-QTOFsplash10-0a6s-0006224900-f4742cfd25e169006a712016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Digitoxin 20V, Positive-QTOFsplash10-0a70-0319222100-bea3c6b184e571520ea62016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Digitoxin 40V, Positive-QTOFsplash10-057i-1529132100-9064e603378164f3a6ff2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Digitoxin 10V, Negative-QTOFsplash10-03xs-0114111900-18fd68a867e967c9eb962016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Digitoxin 20V, Negative-QTOFsplash10-006t-1309122200-4bd32c7f47afcb5b41e82016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Digitoxin 40V, Negative-QTOFsplash10-0f7k-4109220000-0aa801db64fdf30613472016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Digitoxin 10V, Positive-QTOFsplash10-014i-0113001900-f5dd1ea4cb72d5606efa2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Digitoxin 20V, Positive-QTOFsplash10-03yi-1920000300-3b483a0363bee036e99d2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Digitoxin 40V, Positive-QTOFsplash10-07it-3911010000-a2fc3b8d5a5637c01cbd2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Digitoxin 10V, Negative-QTOFsplash10-0w30-0701396700-e02084f39bd1fc586dee2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Digitoxin 20V, Negative-QTOFsplash10-03fu-4900001400-f7f7a9a96401f1317dd02021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Digitoxin 40V, Negative-QTOFsplash10-01r6-5901001400-067cacc939d1c902b4c32021-10-11Wishart LabView Spectrum

NMR Spectra

Spectrum TypeDescriptionDeposition DateSourceView
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01396 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01396 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01396
Phenol Explorer Compound IDNot Available
FooDB IDFDB006525
KNApSAcK IDC00003617
Chemspider ID389987
KEGG Compound IDC06955
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkDigitoxin
METLIN IDNot Available
PubChem Compound441207
PDB IDNot Available
ChEBI ID28544
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Kurowski V, Iven H, Djonlagic H: Treatment of a patient with severe digitoxin intoxication by Fab fragments of anti-digitalis antibodies. Intensive Care Med. 1992;18(7):439-42. [PubMed:1469187 ]
  2. Johansson S, Lindholm P, Gullbo J, Larsson R, Bohlin L, Claeson P: Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells. Anticancer Drugs. 2001 Jun;12(5):475-83. [PubMed:11395576 ]
  3. Hippius M, Humaid B, Sicker T, Hoffmann A, Gottler M, Hasford J: Adverse drug reaction monitoring--digitoxin overdosage in the elderly. Int J Clin Pharmacol Ther. 2001 Aug;39(8):336-43. [PubMed:11515708 ]
  4. Belz GG, Breithaupt-Grogler K, Osowski U: Treatment of congestive heart failure--current status of use of digitoxin. Eur J Clin Invest. 2001;31 Suppl 2:10-7. [PubMed:11525233 ]
  5. Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9. [PubMed:11413487 ]
  6. Watson AD: Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems. J Lipid Res. 2006 Oct;47(10):2101-11. Epub 2006 Aug 10. [PubMed:16902246 ]
  7. Sethi JK, Vidal-Puig AJ: Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res. 2007 Jun;48(6):1253-62. Epub 2007 Mar 20. [PubMed:17374880 ]
  8. Lingwood D, Simons K: Lipid rafts as a membrane-organizing principle. Science. 2010 Jan 1;327(5961):46-50. doi: 10.1126/science.1174621. [PubMed:20044567 ]
  9. Gunstone, Frank D., John L. Harwood, and Albert J. Dijkstra (2007). The lipid handbook with CD-ROM. CRC Press.

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone.
Gene Name:
CYP11A1
Uniprot ID:
P05108
Molecular weight:
60101.87
References
  1. Wang SW, Lin H, Hwang JJ, Wang PS: Inhibition of testosterone secretion by digitoxin in rat testicular interstitial cells. J Cell Biochem. 1999 Jul 1;74(1):74-80. [PubMed:10381263 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in ATP binding
Specific function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A1
Uniprot ID:
P05023
Molecular weight:
112895.01
References
  1. Chen JJ, Wang PS, Chien EJ, Wang SW: Direct inhibitory effect of digitalis on progesterone release from rat granulosa cells. Br J Pharmacol. 2001 Apr;132(8):1761-8. [PubMed:11309248 ]
  2. Marcus FI, Ryan JN, Stafford MG: The reactivity of derivatives of digoxin and digitoxin as measured by the Na-K-atpase displacement assay and by radioimmunoassay. J Lab Clin Med. 1975 Apr;85(4):610-20. [PubMed:123547 ]
  3. Prignitz R, Frohlich D, Hoffmeister G: [Influence of roentgen rays on electrolyte changes and metabolism of the myocardium. VII. Radiation-induced inhibition of the sodium- and potassium--activated microscomal-trasport ATPase]. Strahlentherapie. 1976 Apr;151(4):356-65. [PubMed:131389 ]
  4. Bluschke V, Bonn R, Greeff K: Increase in the (Na+ + K+)-ATPase activity in heart muscle after chronic treatment with digitoxin or potassium deficient diet. Eur J Pharmacol. 1976 May;37(1):189-91. [PubMed:132355 ]
  5. Fricke U: [New aspects on the mode of action of cardiac glycosides]. Fortschr Med. 1976 Nov 11;94(32):1037-45. [PubMed:136410 ]
  6. Hauck C, Potter T, Bartz M, Wittwer T, Wahlers T, Mehlhorn U, Scheiner-Bobis G, McDonough AA, Bloch W, Schwinger RH, Muller-Ehmsen J: Isoform specificity of cardiac glycosides binding to human Na+,K+-ATPase alpha1beta1, alpha2beta1 and alpha3beta1. Eur J Pharmacol. 2009 Nov 10;622(1-3):7-14. doi: 10.1016/j.ejphar.2009.08.039. Epub 2009 Sep 12. [PubMed:19751721 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Pauli-Magnus C, Murdter T, Godel A, Mettang T, Eichelbaum M, Klotz U, Fromm MF: P-glycoprotein-mediated transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin. Naunyn Schmiedebergs Arch Pharmacol. 2001 Mar;363(3):337-43. [PubMed:11284449 ]
General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids
Gene Name:
SLCO1A2
Uniprot ID:
P46721
Molecular weight:
74144.1
References
  1. Bossuyt X, Muller M, Hagenbuch B, Meier PJ: Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver. J Pharmacol Exp Ther. 1996 Mar;276(3):891-6. [PubMed:8786566 ]
General function:
Involved in transporter activity
Specific function:
Organic anion transporter, capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. May participate in the regulation of membrane transport of ouabain. Involved in the uptake of the dipeptidyl peptidase-4 inhibitor sitagliptin and hence may play a role in its transport into and out of renal proximal tubule cells. May be involved in the first step of the transport pathway of digoxin and various compounds into the urine in the kidney. May be involved in sperm maturation by enabling directed movement of organic anions and compounds within or between cells. This ion- transporting process is important to maintain the strict epididymal homeostasis necessary for sperm maturation. May have a role in secretory functions since seminal vesicle epithelial cells are assumed to secrete proteins involved in decapacitation by modifying surface proteins to facilitate the acquisition of the ability to fertilize the egg
Gene Name:
SLCO4C1
Uniprot ID:
Q6ZQN7
Molecular weight:
78947.5
References
  1. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T: Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74. Epub 2004 Mar 1. [PubMed:14993604 ]