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Record Information
Version2.0
Creation Date2009-07-15 20:45:52 UTC
Update Date2014-12-24 20:25:49 UTC
Accession NumberT3D2672
Identification
Common NameAzaspiracid
ClassSmall Molecule
DescriptionAzaspiracid is found in mollusks. Azaspiracid is an alkaloid from Mytilus edulis (blue mussel). Shellfish toxin.
Compound Type
  • Amine
  • Animal Toxin
  • Ether
  • Food Toxin
  • Marine Toxin
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Azaspiracid-1
Chemical FormulaC47H71NO12
Average Molecular Mass842.066 g/mol
Monoisotopic Mass841.498 g/mol
CAS Registry Number214899-21-5
IUPAC Name(4E)-5-[(2R,3aS,5R,5'R,6S,6''S,7aS)-2-[(S)-hydroxy[(2R,3R,5S,6S)-2-hydroxy-3,5-dimethyl-6-{3-[(1'S,2R,2'S,3R,5S,6'S,8'R,10'R)-3,5,10'-trimethyl-3',7',12'-trioxaspiro[piperidine-2,4'-tricyclo[6.3.1.0²,⁶]dodecane]-8'-yl]prop-1-en-2-yl}oxan-2-yl]methyl]-6-methyl-2,3,3a,5'',6,6'',7,7a-octahydrodispiro[furo[3,2-b]pyran-5,2'-oxolane-5',2''-pyran]-6''-yl]pent-4-enoic acid
Traditional Name(4E)-5-[(2R,3aS,5R,5'R,6S,6''S,7aS)-2-[(S)-hydroxy[(2R,3R,5S,6S)-2-hydroxy-3,5-dimethyl-6-{3-[(1'S,2R,2'S,3R,5S,6'S,8'R,10'R)-3,5,10'-trimethyl-3',7',12'-trioxaspiro[piperidine-2,4'-tricyclo[6.3.1.0²,⁶]dodecane]-8'-yl]prop-1-en-2-yl}oxan-2-yl]methyl]-6-methyl-2,3,3a,5'',6,6'',7,7a-octahydrodispiro[furo[3,2-b]pyran-5,2'-oxolane-5',2''-pyran]-6''-yl]pent-4-enoic acid
SMILES[H]\C(CCC(O)=O)=C(\[H])[C@]1([H])CC=C[C@]2(CC[C@]3(O2)O[C@@]2([H])C[C@@]([H])(O[C@@]2([H])C[C@]3([H])C)[C@]([H])(O)[C@]2(O)O[C@]([H])(C(=C)C[C@]34C[C@]([H])(C)C[C@]([H])(O3)[C@]3([H])O[C@@]5(C[C@]3([H])O4)NC[C@@]([H])(C)C[C@@]5([H])C)[C@@]([H])(C)C[C@@]2([H])C)O1
InChI IdentifierInChI=1S/C47H71NO12/c1-26-18-36-41-38(24-45(58-41)30(5)17-27(2)25-48-45)56-44(22-26,55-36)23-29(4)40-28(3)19-32(7)47(52,59-40)42(51)37-21-35-34(53-37)20-31(6)46(57-35)16-15-43(60-46)14-10-12-33(54-43)11-8-9-13-39(49)50/h8,10-11,14,26-28,30-38,40-42,48,51-52H,4,9,12-13,15-25H2,1-3,5-7H3,(H,49,50)/b11-8+/t26-,27+,28+,30-,31+,32-,33-,34+,35+,36+,37-,38+,40+,41+,42+,43+,44-,45-,46-,47-/m1/s1
InChI KeyInChIKey=AHFHSIVCLPAESC-SJVADWSCSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as azaspirodecane derivatives. These are organic compounds containing a spirodecane moiety with at least one nitrogen atom.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassAzaspirodecane derivatives
Direct ParentAzaspirodecane derivatives
Alternative Parents
Substituents
  • Azaspirodecane
  • Furopyran
  • Medium-chain fatty acid
  • Hydroxy fatty acid
  • Amino fatty acid
  • Ketal
  • Heterocyclic fatty acid
  • Monosaccharide
  • Meta-dioxane
  • Oxane
  • Piperidine
  • Pyran
  • Fatty acyl
  • Fatty acid
  • Unsaturated fatty acid
  • Furan
  • Tetrahydrofuran
  • Hemiacetal
  • Secondary alcohol
  • Hemiaminal
  • Acetal
  • Carboxylic acid derivative
  • Carboxylic acid
  • Dialkyl ether
  • Ether
  • Oxacycle
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Alcohol
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Carbonyl group
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Actin Cytoskeleton
  • Actin Filament
  • Cytoskeleton
  • Extracellular
  • Focal adhesion
  • Golgi apparatus
  • Membrane
  • Microtubule
  • Plasma Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
EndocytosisNot Availablemap04144
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceColorless amorphorous solid (10).
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0018 mg/mLALOGPS
logP3.79ALOGPS
logP4.95ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)3.95ChemAxon
pKa (Strongest Basic)9.32ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area163.63 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity221.81 m3·mol-1ChemAxon
Polarizability93.43 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00ec-0109300030-a602af554f2eefaac6beView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-2409021000-e565e752e9cd35713891View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00fr-3901000000-9b7dcd2b450c62ab197eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-002e-2622982040-7d3136f20dbc01b585baView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-08ml-0295322340-b5333fa2568e07f2eebeView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014i-1910000000-5763e14aa049c6d93e57View in MoNA
Toxicity Profile
Route of ExposureOral (2) ; inhalation (2) ; dermal (2) ; eye contact (2)
Mechanism of ToxicityAzaspiracid-4 dose-dependent inhibits the increase in cytosolic Ca2+ levels induced by thapsigargin (Tg) (3). Azaspiracid-2 and Azaspiracid-3 clearly increase cytosolic cAMP levels of human lymphocytes (4).
MetabolismNot Available
Toxicity ValuesLD50: 500-600 mg/kg (Oral, Mouse) (11)
Lethal Dose150 ug/kg for mice. (11)
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesExperimentally in cancer research. The toxin is also found in shellfish (2).
Minimum Risk LevelNot Available
Health EffectsPossibly gastroenteritis (1).
SymptomsAbdominal heaviness, vomiting, and profuse watery diarrhea; also nausea, vomiting, and stomach cramps (2, 6).
TreatmentEstablish a patent airway. Anticipate seizures and treat if necessary. For eye contamination, flush eyes immediately with water. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Cover skin burns with dry sterile dressings after decontamination. (12)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB33805
PubChem Compound ID21593892
ChEMBL IDNot Available
ChemSpider ID10216857
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDAzaspiracid
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D2672.pdf
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Klontz KC, Abraham A, Plakas SM, Dickey RW: Mussel-associated azaspiracid intoxication in the United States. Ann Intern Med. 2009 Mar 3;150(5):361. [19258569 ]
  3. Alfonso A, Roman Y, Vieytes MR, Ofuji K, Satake M, Yasumoto T, Botana LM: Azaspiracid-4 inhibits Ca2+ entry by stored operated channels in human T lymphocytes. Biochem Pharmacol. 2005 Jun 1;69(11):1627-36. Epub 2005 Apr 20. [15896342 ]
  4. Roman Y, Alfonso A, Vieytes MR, Ofuji K, Satake M, Yasumoto T, Botana LM: Effects of Azaspiracids 2 and 3 on intracellular cAMP, [Ca2+], and pH. Chem Res Toxicol. 2004 Oct;17(10):1338-49. [15487894 ]
  5. These A, Scholz J, Preiss-Weigert A: Sensitive method for the determination of lipophilic marine biotoxins in extracts of mussels and processed shellfish by high-performance liquid chromatography-tandem mass spectrometry based on enrichment by solid-phase extraction. J Chromatogr A. 2009 May 22;1216(21):4529-38. doi: 10.1016/j.chroma.2009.03.062. Epub 2009 Mar 27. [19362722 ]
  6. Garcia BG, Wei Y, Moron JA, Lin RZ, Javitch JA, Galli A: Akt is essential for insulin modulation of amphetamine-induced human dopamine transporter cell-surface redistribution. Mol Pharmacol. 2005 Jul;68(1):102-9. Epub 2005 Mar 28. [15795321 ]
  7. Olson KR (ed) (2004). Poisoning & Drug Overdose. 4th ed. New York, NY: Lange Medical Books/McGraw-Hill.
  8. Currance PL, Clements B, Bronstein AC (eds) (2005). Emergency Care For Hazardous Materials Exposure. 3rd ed. St. Louis, MO: Elsevier Mosby.
  9. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
  10. Food and Agricultural Organization of the United Nations (2004). Marine Biotoxins: Azaspiracid Shellfish Poisoning (AZP). [Link]
  11. Patocka J, Hrdina V, Merka V, and Hrdina H (2005). Azaspiracid: a New Marine Toxin. The ASA Newsletter 2005 Oct;110:16-19. [Link]
  12. TOXNET - Azaspiracid [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
References
  1. Twiner MJ, Doucette GJ, Rasky A, Huang XP, Roth BL, Sanguinetti MC: Marine algal toxin azaspiracid is an open-state blocker of hERG potassium channels. Chem Res Toxicol. 2012 Sep 17;25(9):1975-84. doi: 10.1021/tx300283t. Epub 2012 Aug 10. [22856456 ]