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Record Information
Version2.0
Creation Date2009-07-06 21:35:29 UTC
Update Date2014-12-24 20:25:47 UTC
Accession NumberT3D2626
Identification
Common Namealpha-Agatoxin
ClassSmall Molecule
DescriptionAgatoxins are a class of chemically diverse polyamine and peptide toxins which are isolated from the venom of various spiders, in particular the North American funnel-web spider (Agelenopsis aperta), after which agatoxins are named. alpha-Agatoxins are composed of polyamines which are attached to an aromatic moiety. They block the glutamate-activated receptor channels in the neuronal postsynaptic terminals of insects and mammals. (1)
Compound Type
  • Amide
  • Amine
  • Animal Toxin
  • Natural Compound
  • Organic Compound
  • Spider Toxin
Chemical Structure
Thumb
Synonyms
Synonym
a-Agatoxin
Agatoxin 489
α-Agatoxin
Chemical FormulaC26H47N7O2
Average Molecular Mass489.697 g/mol
Monoisotopic Mass489.379 g/mol
CAS Registry Number128549-96-2
IUPAC NameN-[3-(17-amino-1-hydroxy-1,5,9,14-tetraazaheptadecan-1-yl)propyl]-2-(1H-indol-3-yl)acetamide
Traditional NameN-[3-(17-amino-1-hydroxy-1,5,9,14-tetraazaheptadecan-1-yl)propyl]-2-(1H-indol-3-yl)acetamide
SMILESNCCCNCCCCNCCCNCCCN(O)CCCNC(=O)CC1=CNC2=CC=CC=C12
InChI IdentifierInChI=1S/C26H47N7O2/c27-11-5-14-28-12-3-4-13-29-15-6-16-30-17-7-19-33(35)20-8-18-31-26(34)21-23-22-32-25-10-2-1-9-24(23)25/h1-2,9-10,22,28-30,32,35H,3-8,11-21,27H2,(H,31,34)
InChI KeyInChIKey=LIURIBSBVUMOJS-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as 3-alkylindoles. These are compounds containing an indole moiety that carries an alkyl chain at the 3-position.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassIndoles and derivatives
Direct Parent3-alkylindoles
Alternative Parents
Substituents
  • 3-alkylindole
  • Substituted pyrrole
  • Benzenoid
  • Pyrrole
  • Heteroaromatic compound
  • Amino acid or derivatives
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Carboxylic acid derivative
  • Secondary aliphatic amine
  • Secondary amine
  • Azacycle
  • N-organohydroxylamine
  • Organopnictogen compound
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Organic nitrogen compound
  • Amine
  • Organic oxide
  • Hydrocarbon derivative
  • Carbonyl group
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot 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
Water Solubility0.0116 mg/mLALOGPS
logP1.34ALOGPS
logP-0.69ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)15.34ChemAxon
pKa (Strongest Basic)11.12ChemAxon
Physiological Charge4ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area130.47 Å2ChemAxon
Rotatable Bond Count22ChemAxon
Refractivity144.75 m3·mol-1ChemAxon
Polarizability59.13 Å3ChemAxon
Number of Rings2ChemAxon
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, Positivesplash10-008c-1549700000-501119752a578c927008View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-06sl-4944000000-75339ff8fec08d60e067View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-056c-3930000000-8d15f6829defd32f5195View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0241900000-5cbf1504e4ef06035b22View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-3893400000-381e821411fe14a6dfa7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00xu-6920000000-bb3ae0dbaf92d949a39fView in MoNA
Toxicity Profile
Route of ExposureInjection (sting/bite) (3)
Mechanism of Toxicityalpha-Agatoxins block the glutamate-activated receptor channels in the neuronal postsynaptic terminals of insects and mammals, preventing excitory junction potential from developing. (1)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesAgatoxins are a class of chemically diverse polyamine and peptide toxins which are isolated from the venom of various spiders, in particular the North American funnel-web spider (Agelenopsis aperta). (1)
Minimum Risk LevelNot Available
Health Effectsalpha-Agatoxin causes a rapid reversible paralysis. Death can result from progressive hypotension or possibly raised intracranial pressure resulting from cerebral oedema. (1, 2)
SymptomsThe bites of funnel-web spiders may cause tingling around the mouth and tongue, facial muscle twitching, nausea, vomiting, profuse sweating, salivation, and shortness of breath. Patients may also rapidly develop agitation, confusion and coma associated with hypertension, metabolic acidosis, dilation of the pupils, generalised muscle twitching and pulmonary oedema. (2)
TreatmentFirst aid for funnel-web bites consists of applying a pressure immobilization bandage to slow venom movement. Further supportive care may be necessary, but the mainstay of treatment is antivenom. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID131007
ChEMBL IDNot Available
ChemSpider ID115840
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDalpha-Agatoxin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Wikipedia. Agatoxin. Last Updated 28 March 2009. [Link]
  2. Wikipedia. Australian funnel-web spider. Last Updated 6 July 2009. [Link]
  3. Wikipedia. Spider toxin. Last Updated 9 January 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Pdz domain binding
Specific Function:
Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
Gene Name:
GRIA1
Uniprot ID:
P42261
Molecular Weight:
101505.245 Da
References
  1. Wikipedia. Agatoxin. Last Updated 28 March 2009. [Link]
General Function:
Ionotropic glutamate receptor activity
Specific Function:
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
Gene Name:
GRIA2
Uniprot ID:
P42262
Molecular Weight:
98820.32 Da
References
  1. Wikipedia. Agatoxin. Last Updated 28 March 2009. [Link]
General Function:
Extracellular-glutamate-gated ion channel activity
Specific Function:
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
Gene Name:
GRIA3
Uniprot ID:
P42263
Molecular Weight:
101155.975 Da
References
  1. Wikipedia. Agatoxin. Last Updated 28 March 2009. [Link]
General Function:
Ionotropic glutamate receptor activity
Specific Function:
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
Gene Name:
GRIA4
Uniprot ID:
P48058
Molecular Weight:
100870.085 Da
References
  1. Wikipedia. Agatoxin. Last Updated 28 March 2009. [Link]
General Function:
Voltage-gated cation channel activity
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors (By similarity).
Gene Name:
GRIN1
Uniprot ID:
Q05586
Molecular Weight:
105371.945 Da
References
  1. Wikipedia. Agatoxin. Last Updated 28 March 2009. [Link]
General Function:
Zinc ion binding
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits.
Gene Name:
GRIN2A
Uniprot ID:
Q12879
Molecular Weight:
165281.215 Da
References
  1. Wikipedia. Agatoxin. Last Updated 28 March 2009. [Link]
General Function:
Zinc ion binding
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity).
Gene Name:
GRIN2B
Uniprot ID:
Q13224
Molecular Weight:
166365.885 Da
References
  1. Wikipedia. Agatoxin. Last Updated 28 March 2009. [Link]
General Function:
Nmda glutamate receptor activity
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine.
Gene Name:
GRIN2C
Uniprot ID:
Q14957
Molecular Weight:
134207.77 Da
References
  1. Wikipedia. Agatoxin. Last Updated 28 March 2009. [Link]
General Function:
Nmda glutamate receptor activity
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine.
Gene Name:
GRIN2D
Uniprot ID:
O15399
Molecular Weight:
143750.685 Da
References
  1. Wikipedia. Agatoxin. Last Updated 28 March 2009. [Link]
General Function:
Protein phosphatase 2a binding
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism (By similarity).
Gene Name:
GRIN3A
Uniprot ID:
Q8TCU5
Molecular Weight:
125464.07 Da
References
  1. Wikipedia. Agatoxin. Last Updated 28 March 2009. [Link]
General Function:
Nmda glutamate receptor activity
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine.
Gene Name:
GRIN3B
Uniprot ID:
O60391
Molecular Weight:
112990.98 Da
References
  1. Wikipedia. Agatoxin. Last Updated 28 March 2009. [Link]