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Identification
NameOuabain
Accession NumberDB01092  (APRD00135)
Typesmall molecule
Groupsapproved
Description

A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA-K(+)-exchanging ATPase. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
3-(alpha-L-Rhamnopyranosyloxy)-1beta,5beta,11alpha,14,19-pentahydroxy-5beta-card-20(22)-enolideNot AvailableNot Available
G-StrophanthinNot AvailableNot Available
Ouabagenin L-RhamnosideNot AvailableNot Available
Ouabagenin-L-rhamnosidNot AvailableNot Available
OuabainNot AvailableNot Available
Ouabain anhydrousNot AvailableNot Available
OuabaineNot AvailableNot Available
OubainNot AvailableNot Available
StrodivalNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
StrodivalNot Available
Brand mixturesNot Available
Categories
CAS number630-60-4
WeightAverage: 584.6525
Monoisotopic: 584.283276872
Chemical FormulaC29H44O12
InChI KeyLPMXVESGRSUGHW-HBYQJFLCSA-N
InChI
InChI=1S/C29H44O12/c1-13-22(34)23(35)24(36)25(40-13)41-15-8-19(32)28(12-30)21-17(3-5-27(28,37)9-15)29(38)6-4-16(14-7-20(33)39-11-14)26(29,2)10-18(21)31/h7,13,15-19,21-25,30-32,34-38H,3-6,8-12H2,1-2H3/t13-,15-,16+,17+,18+,19+,21+,22-,23+,24+,25-,26+,27-,28+,29-/m0/s1
IUPAC Name
4-[(1S,2R,3R,5S,7S,10R,11S,14R,15R,17R)-3,7,11,17-tetrahydroxy-2-(hydroxymethyl)-15-methyl-5-{[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy}tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-14-yl]-2,5-dihydrofuran-2-one
SMILES
[H][C@@]12CC[C@]3(O)C[C@H](C[C@@H](O)[C@]3(CO)[C@@]1([H])[C@H](O)C[C@]1(C)[C@H](CC[C@]21O)C1=CC(=O)OC1)O[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassSteroid Lactones
Direct parentCardenolide Glycosides and Derivatives
Alternative parentsSteroidal Glycosides; Hydroxysteroids; O-glycosyl Compounds; Hexoses; Cyclohexanols; Butenolides; Oxanes; Tertiary Alcohols; 1,2-Diols; Cyclic Alcohols and Derivatives; Carboxylic Acid Esters; Primary Alcohols; Acetals; Polyamines
Substituentssteroidal glycoside; 19-hydroxy-steroid; 14-hydroxy-steroid; 11-hydroxy-steroid; 1-hydroxy-steroid; 5-hydroxy-steroid; glycosyl compound; o-glycosyl compound; hexose monosaccharide; cyclohexanol; monosaccharide; saccharide; oxane; 2-furanone; dihydrofuran; tertiary alcohol; cyclic alcohol; carboxylic acid ester; polyol; secondary alcohol; 1,2-diol; primary alcohol; ether; acetal; polyamine; carboxylic acid derivative; alcohol
Classification descriptionThis compound belongs to the cardenolide glycosides and derivatives. These are compounds containing a carbohydrate glycosidically bound to the cardenolide moiety.
Pharmacology
IndicationFor the treatment of atrial fibrillation and flutter and heart failure
PharmacodynamicsOuabain, a cardiac glycoside similar to digitoxin, is used to treat congestive heart failure and supraventricular arrhythmias due to reentry mechanisms, and to control ventricular rate in the treatment of chronic atrial fibrillation.
Mechanism of actionOuabain 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). Ouabain 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding60%
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9064
Blood Brain Barrier - 0.5562
Caco-2 permeable - 0.9052
P-glycoprotein substrate Substrate 0.8773
P-glycoprotein inhibitor I Non-inhibitor 0.5313
P-glycoprotein inhibitor II Non-inhibitor 0.6281
Renal organic cation transporter Non-inhibitor 0.8177
CYP450 2C9 substrate Non-substrate 0.8563
CYP450 2D6 substrate Non-substrate 0.8844
CYP450 3A4 substrate Substrate 0.685
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9242
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9271
CYP450 3A4 substrate Non-inhibitor 0.9241
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9179
Ames test Non AMES toxic 0.9172
Carcinogenicity Non-carcinogens 0.9638
Biodegradation Not ready biodegradable 0.9784
Rat acute toxicity 4.7797 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9551
hERG inhibition (predictor II) Inhibitor 0.8457
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point200 °CPhysProp
water solubility1.03E+004 mg/LNot Available
logP-2.00SANGSTER (1994)
Predicted Properties
PropertyValueSource
water solubility4.61e+00 g/lALOGPS
logP-1ALOGPS
logP-2.8ChemAxon
logS-2.1ALOGPS
pKa (strongest acidic)7.18ChemAxon
pKa (strongest basic)-2.9ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count11ChemAxon
hydrogen donor count8ChemAxon
polar surface area206.6ChemAxon
rotatable bond count4ChemAxon
refractivity140.83ChemAxon
polarizability59.93ChemAxon
number of rings6ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Gao J, Wymore RS, Wang Y, Gaudette GR, Krukenkamp IB, Cohen IS, Mathias RT: Isoform-specific stimulation of cardiac Na/K pumps by nanomolar concentrations of glycosides. J Gen Physiol. 2002 Apr;119(4):297-312. Pubmed
  2. Saunders R, Scheiner-Bobis G: Ouabain stimulates endothelin release and expression in human endothelial cells without inhibiting the sodium pump. Eur J Biochem. 2004 Mar;271(5):1054-62. Pubmed
  3. Hamlyn JM, Blaustein MP, Bova S, DuCharme DW, Harris DW, Mandel F, Mathews WR, Ludens JH: Identification and characterization of a ouabain-like compound from human plasma. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6259-63. Pubmed
  4. Hamlyn JM, Laredo J, Shah JR, Lu ZR, Hamilton BP: 11-hydroxylation in the biosynthesis of endogenous ouabain: multiple implications. Ann N Y Acad Sci. 2003 Apr;986:685-93. Pubmed
  5. Laredo J, Hamilton BP, Hamlyn JM: Ouabain is secreted by bovine adrenocortical cells. Endocrinology. 1994 Aug;135(2):794-7. Pubmed
External Links
ResourceLink
KEGG DrugD00112
KEGG CompoundC01443
PubChem Compound439501
PubChem Substance46505479
ChemSpider388599
ChEBI472805
ChEMBLCHEMBL222863
Therapeutic Targets DatabaseDAP000465
PharmGKBPA163522138
WikipediaOuabain
ATC CodesC01AC01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Sodium/potassium-transporting ATPase subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium/potassium-transporting ATPase subunit alpha-1 P05023 Details

References:

  1. Mentre P, Debey P: An unexpected effect of an ouabain-sensitive ATPase activity on the amount of antigen-antibody complexes formed in situ. Cell Mol Biol (Noisy-le-grand). 1999 Sep;45(6):781-91. Pubmed
  2. Qazzaz HM, El-Masri MA, Stolowich NJ, Valdes R Jr: Two biologically active isomers of dihydroouabain isolated from a commercial preparation. Biochim Biophys Acta. 1999 Nov 16;1472(3):486-97. Pubmed
  3. Tao QF, Hollenberg NK, Graves SW: Sodium pump inhibition and regional expression of sodium pump alpha-isoforms in lens. Hypertension. 1999 Nov;34(5):1168-74. Pubmed
  4. Hawke TJ, Willmets RG, Lindinger MI: K+ transport in resting rat hind-limb skeletal muscle in response to paraxanthine, a caffeine metabolite. Can J Physiol Pharmacol. 1999 Nov;77(11):835-43. Pubmed
  5. Almotrefi AA, Basco C, Moorji A, Dzimiri N: Class I antiarrhythmic drug effects on ouabain binding to guinea pig cardiac Na+ -K+ ATPase. Can J Physiol Pharmacol. 1999 Nov;77(11):866-70. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

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. Epub 2009 Nov 24. Pubmed

Transporters

1. Solute carrier organic anion transporter family member 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1A2 P46721 Details

References:

  1. Li L, Lee TK, Meier PJ, Ballatori N: Identification of glutathione as a driving force and leukotriene C4 as a substrate for oatp1, the hepatic sinusoidal organic solute transporter. J Biol Chem. 1998 Jun 26;273(26):16184-91. Pubmed
  2. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. Pubmed
  3. Bossuyt X, Muller M, Meier PJ: Multispecific amphipathic substrate transport by an organic anion transporter of human liver. J Hepatol. 1996 Nov;25(5):733-8. Pubmed
  4. Hagenbuch B, Adler ID, Schmid TE: Molecular cloning and functional characterization of the mouse organic-anion-transporting polypeptide 1 (Oatp1) and mapping of the gene to chromosome X. Biochem J. 2000 Jan 1;345 Pt 1:115-20. Pubmed
  5. 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
  6. Eckhardt U, Schroeder A, Stieger B, Hochli M, Landmann L, Tynes R, Meier PJ, Hagenbuch B: Polyspecific substrate uptake by the hepatic organic anion transporter Oatp1 in stably transfected CHO cells. Am J Physiol. 1999 Apr;276(4 Pt 1):G1037-42. Pubmed

2. Solute carrier family 22 member 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 8 Q8TCC7 Details

References:

  1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. Pubmed
  2. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. Pubmed

3. Solute carrier organic anion transporter family member 4C1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 4C1 Q6ZQN7 Details

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

4. Solute carrier organic anion transporter family member 1B3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B3 Q9NPD5 Details

References:

  1. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. Pubmed

5. Solute carrier organic anion transporter family member 1C1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1C1 Q9NYB5 Details

References:

  1. Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ: Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96. Pubmed

6. Solute carrier organic anion transporter family member 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

References:

  1. van Montfoort JE, Schmid TE, Adler ID, Meier PJ, Hagenbuch B: Functional characterization of the mouse organic-anion-transporting polypeptide 2. Biochim Biophys Acta. 2002 Aug 19;1564(1):183-8. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13