Tmic
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Record Information
Version2.0
Creation Date2009-07-03 21:14:35 UTC
Update Date2014-12-24 20:25:32 UTC
Accession NumberT3D2462
Identification
Common NamePalytoxin
ClassSmall Molecule
DescriptionPalytoxin is a complex marine natural product containing 71 asymmetric centers. Palytoxin, isolated from soft coral, is considered to be one of the most toxic non-peptide substances known, second only to maitotoxin (5).
Compound Type
  • Amine
  • Animal Toxin
  • Ether
  • Lachrymator
  • Marine Toxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
SynonymsNot Available
Chemical FormulaC129H223N3O53
Average Molecular Mass2664.139 g/mol
Monoisotopic Mass2662.485 g/mol
CAS Registry Number77734-91-9
IUPAC Name(2S,3R,5R,6E,8R,9S)-10-[(2R,3R,4R,5S,6R)-6-[(1S,2R,3S,4S,5R,11S)-12-[(1R,3S,5S,7R)-5-[(8S)-9-[(2R,3R,4R,5R,6S)-6-[(2S,3S,4E,6S,9R,10R)-10-[(2S,4R,5S,6R)-6-[(2R,3R)-4-[(2R,3S,4R,5R,6S)-6-[(2S,3Z,5E,8R,9S,10R,12Z,17S,18R,19R,20R)-20-{[(2R,3R,4R,5S,6R)-6-[(1Z,3S)-5-[(1S,3R,5R,7R)-7-{2-[(2R,3R,5S)-5-(aminomethyl)-3-hydroxyoxolan-2-yl]ethyl}-2,6-dioxabicyclo[3.2.1]octan-3-yl]-3-hydroxypent-1-en-1-yl]-3,4,5-trihydroxyoxan-2-yl]methyl}-2,8,9,10,17,18,19-heptahydroxy-14-methylidenehenicosa-3,5,12-trien-1-yl]-3,4,5-trihydroxyoxan-2-yl]-2,3-dihydroxybutyl]-4,5-dihydroxyoxan-2-yl]-2,6,9,10-tetrahydroxy-3-methyldec-4-en-1-yl]-3,4,5,6-tetrahydroxyoxan-2-yl]-8-hydroxynonyl]-1,3-dimethyl-6,8-dioxabicyclo[3.2.1]octan-7-yl]-1,2,3,4,5-pentahydroxy-11-methyldodecyl]-3,4,5-trihydroxyoxan-2-yl]-2,5,8,9-tetrahydroxy-N-[(1E)-2-[(3-hydroxypropyl)-C-hydroxycarbonimidoyl]eth-1-en-1-yl]-3,7-dimethyldec-6-enimidic acid
Traditional Name(2S,3R,5R,6E,8R,9S)-10-[(2R,3R,4R,5S,6R)-6-[(1S,2R,3S,4S,5R,11S)-12-[(1R,3S,5S,7R)-5-[(8S)-9-[(2R,3R,4R,5R,6S)-6-[(2S,3S,4E,6S,9R,10R)-10-[(2S,4R,5S,6R)-6-[(2R,3R)-4-[(2R,3S,4R,5R,6S)-6-[(2S,3Z,5E,8R,9S,10R,12Z,17S,18R,19R,20R)-20-{[(2R,3R,4R,5S,6R)-6-[(1Z,3S)-5-[(1S,3R,5R,7R)-7-{2-[(2R,3R,5S)-5-(aminomethyl)-3-hydroxyoxolan-2-yl]ethyl}-2,6-dioxabicyclo[3.2.1]octan-3-yl]-3-hydroxypent-1-en-1-yl]-3,4,5-trihydroxyoxan-2-yl]methyl}-2,8,9,10,17,18,19-heptahydroxy-14-methylidenehenicosa-3,5,12-trien-1-yl]-3,4,5-trihydroxyoxan-2-yl]-2,3-dihydroxybutyl]-4,5-dihydroxyoxan-2-yl]-2,6,9,10-tetrahydroxy-3-methyldec-4-en-1-yl]-3,4,5,6-tetrahydroxyoxan-2-yl]-8-hydroxynonyl]-1,3-dimethyl-6,8-dioxabicyclo[3.2.1]octan-7-yl]-1,2,3,4,5-pentahydroxy-11-methyldodecyl]-3,4,5-trihydroxyoxan-2-yl]-2,5,8,9-tetrahydroxy-N-[(1E)-2-[(3-hydroxypropyl)-C-hydroxycarbonimidoyl]eth-1-en-1-yl]-3,7-dimethyldec-6-enimidic acid
SMILES[H]\C(C[C@@]([H])(O)[C@]([H])(O)[C@]([H])(O)C\C([H])=C(\[H])C(=C)CC[C@]([H])(O)[C@@]([H])(O)[C@]([H])(O)[C@]([H])(C)C[C@@]1([H])O[C@]([H])(C(\[H])=C(\[H])[C@@]([H])(O)CC[C@]2([H])C[C@]3([H])C[C@]([H])(O2)[C@@]([H])(CC[C@@]2([H])O[C@]([H])(CN)C[C@@]2([H])O)O3)[C@@]([H])(O)[C@]([H])(O)[C@@]1([H])O)=C(\[H])/C(/[H])=C(/[H])[C@@]([H])(O)C[C@]1([H])O[C@]([H])(C[C@@]([H])(O)[C@]([H])(O)C[C@@]2([H])O[C@@]([H])(C[C@@]([H])(O)[C@]2([H])O)[C@]([H])(O)[C@]([H])(O)CC[C@]([H])(O)C(\[H])=C(/[H])[C@]([H])(C)[C@@]([H])(O)C[C@]2(O)O[C@]([H])(C[C@@]([H])(O)CCCCCCC[C@@]34C[C@@]([H])(C)C[C@@](C)(O3)[C@@]([H])(C[C@@]([H])(C)CCCCC[C@@]([H])(O)[C@]([H])(O)[C@]([H])(O)[C@@]([H])(O)[C@]([H])(O)[C@@]3([H])O[C@]([H])(C[C@]([H])(O)[C@]([H])(O)C(\C)=C(/[H])[C@]([H])(O)C[C@@]([H])(C)[C@]([H])(O)C(O)=N\C([H])=C(/[H])C(O)=NCCCO)[C@]([H])(O)[C@@]([H])(O)[C@]3([H])O)O4)[C@]([H])(O)[C@@]([H])(O)[C@@]2([H])O)[C@@]([H])(O)[C@]([H])(O)[C@@]1([H])O
InChI IdentifierInChI=1S/C129H223N3O53/c1-63(29-36-82(143)108(157)103(152)69(7)49-93-111(160)117(166)110(159)91(179-93)38-34-71(135)32-35-75-52-76-54-92(176-75)90(177-76)40-39-89-85(146)53-77(62-130)178-89)23-20-28-79(140)105(154)78(139)26-18-13-16-25-72(136)50-94-112(161)118(167)113(162)97(180-94)56-84(145)83(144)55-95-107(156)87(148)58-96(181-95)106(155)81(142)37-33-70(134)31-30-66(4)88(149)61-129(175)125(173)123(172)115(164)99(183-129)51-73(137)24-15-10-9-11-19-42-128-60-65(3)59-127(8,185-128)100(184-128)46-64(2)22-14-12-17-27-80(141)109(158)116(165)120(169)122(171)124-121(170)119(168)114(163)98(182-124)57-86(147)102(151)67(5)47-74(138)48-68(6)104(153)126(174)132-44-41-101(150)131-43-21-45-133/h13,16,18,20,23,25,30-31,34,38,41,44,47,64-66,68-100,102-125,133-149,151-173,175H,1,9-12,14-15,17,19,21-22,24,26-29,32-33,35-37,39-40,42-43,45-46,48-62,130H2,2-8H3,(H,131,150)(H,132,174)/b18-13+,23-20-,25-16-,31-30+,38-34-,44-41+,67-47+/t64-,65-,66-,68+,69+,70+,71-,72+,73-,74-,75+,76+,77-,78+,79+,80+,81+,82-,83+,84+,85+,86-,87+,88-,89+,90+,91+,92-,93+,94-,95+,96-,97+,98+,99+,100+,102+,103+,104-,105-,106+,107-,108+,109-,110+,111-,112-,113+,114-,115-,116-,117-,118+,119+,120+,121-,122-,123+,124-,125+,127+,128-,129-/m0/s1
InChI KeyInChIKey=GZXBNJVQTZZERE-YUOBMYCZSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as terpene glycosides. These are prenol lipids containing a carbohydrate moiety glycosidically bound to a terpene backbone.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassTerpene glycosides
Direct ParentTerpene glycosides
Alternative Parents
Substituents
  • Terpene glycoside
  • C-glycosyl compound
  • Glycosyl compound
  • Monoterpenoid
  • 1,4-dioxepane
  • Ketal
  • Oxepane
  • Dioxepane
  • N-acyl-amine
  • Oxane
  • Fatty acyl
  • Fatty amide
  • Monosaccharide
  • Meta-dioxolane
  • Acrylic acid or derivatives
  • Vinylogous amide
  • Tetrahydrofuran
  • Amino acid or derivatives
  • Hemiacetal
  • Carboxamide group
  • Secondary alcohol
  • Secondary carboxylic acid amide
  • Acetal
  • Alkanolamine
  • Carboxylic acid derivative
  • Dialkyl ether
  • Oxacycle
  • Ether
  • Organoheterocyclic compound
  • Polyol
  • Alcohol
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Carbonyl group
  • Organic oxide
  • Organic oxygen compound
  • Amine
  • Primary amine
  • Primary alcohol
  • Primary aliphatic amine
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Actin Cytoskeleton
  • Actin Filament
  • Apical Membrane
  • Cell junction
  • Cell surface
  • Cytoskeleton
  • Cytosol
  • Endoplasmic reticulum
  • Extracellular
  • Intermediate Filament
  • Membrane
  • Microsome
  • Microtubule
  • Mitochondrion
  • Plasma Membrane
  • Ribosome
  • Sarcoplasmic Reticulum
  • Synaptic Vesicle
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
Arachidonic Acid MetabolismSMP00075 map00590
Cell cycleNot Availablemap04110
Antiarrhythmic DrugsNot AvailableNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP-12ChemAxon
pKa (Strongest Acidic)0.3ChemAxon
pKa (Strongest Basic)9.23ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count56ChemAxon
Hydrogen Donor Count44ChemAxon
Polar Surface Area1012.93 ŲChemAxon
Rotatable Bond Count80ChemAxon
Refractivity667.43 m³·mol⁻¹ChemAxon
Polarizability284.6 ųChemAxon
Number of Rings10ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Toxicity Profile
Route of ExposureIngestion, dermal and eye contact. (1, 2)
Mechanism of ToxicityPalytoxin targets the sodium-potassium pump protein by binding to the molecule such that the molecule is locked in a position where it allows passive transport of both the sodium and potassium ions, thereby destroying the ion gradient that is essential for most cells. It also diminishing the supply of oxygen to the myocardium, and can cause death within minutes. (5, 3).
MetabolismNot Available
Toxicity ValuesLD50: 0.025 ug/kg (Intravenous, Rabbit) (4)
Lethal DoseThe lethal oral dose in humans is 1 to 4 mg. (4)
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesPalytoxin is isolated from soft coral (5).
Minimum Risk LevelNot Available
Health EffectsPalytoxin poisoning can cause multiple clinical effects, including paresthesia, dysguesia, hypertension, respiratory depression, and coma. Other health effects include tachycardia, unstable blood pressure, hemolysis (destruction of red blood cells). The onset of symptoms is rapid, and death usually follows just minutes after. Early death is probably due to intense spasm of the coronary vascular smooth muscle, resulting in marked reduction in blood flow. This may be an early manifestation of what later becomes a general necrotizing effect of palytoxin on blood vessels, which ultimately causes cell destruction throughout the body. The delayed deaths may be the result of a less profound but widespread decrease in blood flow and oxygen supply, causing ischemia and, ultimately, anoxia in major organ systems. Palytoxin can cause marked irritation and tissue injury when applied topically to the skin or eyes of animals. (5, 2).
SymptomsTypical symptoms of palytoxin poisoning are angina-like chest pains, asthma-like breathing difficulties, and an electrocardiogram showing an exaggerated T wave (5).
TreatmentTreatment in humans is symptomatic and supportive. Vasodilators, such as papverine and isosorbide nitrate, can be used as antidotes. The patient can be treated supportively with corticosteroids and a histamine antagonist after dermal exposure. (5, 1)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID4660115
ChEMBL IDCHEMBL1908337
ChemSpider ID28487363
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDPalytoxin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkPalytoxin
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Nordt SP, Wu J, Zahller S, Clark RF, Cantrell FL: Palytoxin poisoning after dermal contact with zoanthid coral. J Emerg Med. 2011 Apr;40(4):397-9. doi: 10.1016/j.jemermed.2009.05.004. Epub 2009 Jul 9. [19545971 ]
  2. Vick JA, Wiles JS: The mechanism of action and treatment of palytoxin poisoning. Toxicol Appl Pharmacol. 1975 Nov;34(2):214-23. [1871 ]
  3. Tosteson MT, Scriven DR, Bharadwaj AK, Kishi Y, Tosteson DC: Interaction of palytoxin with red cells: structure-function studies. Toxicon. 1995 Jun;33(6):799-807. [7676471 ]
  4. Wang DZ: Neurotoxins from marine dinoflagellates: a brief review. Mar Drugs. 2008 Jun 11;6(2):349-71. doi: 10.3390/md20080016. [18728731 ]
  5. Wikipedia. Palytoxin. Last Updated 4 August 2009. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Steroid hormone 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 Da
References
  1. Wikipedia. Palytoxin. Last Updated 4 August 2009. [Link]
General Function:
Steroid hormone 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, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A2
Uniprot ID:
P50993
Molecular Weight:
112264.385 Da
References
  1. Wikipedia. Palytoxin. Last Updated 4 August 2009. [Link]
General Function:
Steroid hormone 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:
ATP1A3
Uniprot ID:
P13637
Molecular Weight:
111747.51 Da
References
  1. Wikipedia. Palytoxin. Last Updated 4 August 2009. [Link]
General Function:
Sodium:potassium-exchanging atpase activity
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. Plays a role in sperm motility.
Gene Name:
ATP1A4
Uniprot ID:
Q13733
Molecular Weight:
114165.44 Da
References
  1. Wikipedia. Palytoxin. Last Updated 4 August 2009. [Link]
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane.Involved in cell adhesion and establishing epithelial cell polarity.
Gene Name:
ATP1B1
Uniprot ID:
P05026
Molecular Weight:
35061.07 Da
References
  1. Wikipedia. Palytoxin. Last Updated 4 August 2009. [Link]
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-2 subunit is not known.Mediates cell adhesion of neurons and astrocytes, and promotes neurite outgrowth.
Gene Name:
ATP1B2
Uniprot ID:
P14415
Molecular Weight:
33366.925 Da
References
  1. Wikipedia. Palytoxin. Last Updated 4 August 2009. [Link]
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-3 subunit is not known.
Gene Name:
ATP1B3
Uniprot ID:
P54709
Molecular Weight:
31512.34 Da
References
  1. Wikipedia. Palytoxin. Last Updated 4 August 2009. [Link]
General Function:
Transporter activity
Specific Function:
May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.
Gene Name:
FXYD2
Uniprot ID:
P54710
Molecular Weight:
7283.265 Da
References
  1. Wikipedia. Palytoxin. Last Updated 4 August 2009. [Link]
General Function:
Temperature-gated cation channel activity
Specific Function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular Weight:
127499.88 Da
References
  1. Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]