Tmic
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Record Information
Version2.0
Creation Date2009-07-23 18:26:08 UTC
Update Date2014-12-24 20:25:57 UTC
Accession NumberT3D3084
Identification
Common NameResiniferatoxin
ClassSmall Molecule
DescriptionResiniferatoxin (RTX) is a plant toxin and ultrapotent capsaicin analog that occurs in various species of plants, such as resin spurge (Euphorbia resinifera). It evokes a powerful irritant effect followed by desensitization and analgesia. (1)
Compound Type
  • Ester
  • Ether
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
Synonyms
Synonym
RTX
Chemical FormulaC37H40O9
Average Molecular Mass628.708 g/mol
Monoisotopic Mass628.267 g/mol
CAS Registry Number57444-62-9
IUPAC Name[(1R,2R,6R,10S,11R,15R,17R)-13-benzyl-6-hydroxy-4,17-dimethyl-5-oxo-15-(prop-1-en-2-yl)-12,14,18-trioxapentacyclo[11.4.1.0¹,¹⁰.0²,⁶.0¹¹,¹⁵]octadeca-3,8-dien-8-yl]methyl 2-(4-hydroxy-3-methoxyphenyl)acetate
Traditional Name[(1R,2R,6R,10S,11R,15R,17R)-13-benzyl-6-hydroxy-4,17-dimethyl-5-oxo-15-(prop-1-en-2-yl)-12,14,18-trioxapentacyclo[11.4.1.0¹,¹⁰.0²,⁶.0¹¹,¹⁵]octadeca-3,8-dien-8-yl]methyl 2-(4-hydroxy-3-methoxyphenyl)acetate
SMILES[H][C@]12OC3(CC4=CC=CC=C4)O[C@]1(C[C@@]([H])(C)[C@]1(O3)[C@]3([H])C=C(C)C(=O)[C@@]3(O)CC(COC(=O)CC3=CC(OC)=C(O)C=C3)=C[C@@]21[H])C(C)=C
InChI IdentifierInChI=1S/C37H40O9/c1-21(2)35-17-23(4)37-27(33(35)44-36(45-35,46-37)19-24-9-7-6-8-10-24)14-26(18-34(41)30(37)13-22(3)32(34)40)20-43-31(39)16-25-11-12-28(38)29(15-25)42-5/h6-15,23,27,30,33,38,41H,1,16-20H2,2-5H3/t23-,27+,30-,33-,34-,35-,36?,37-/m1/s1
InChI KeyInChIKey=DSDNAKHZNJAGHN-IHCAYWNCSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as rhamnofolane and daphnane diterpenoids. These are diterpenoids with a structure based on one the rhamnofolane or daphnane skeleton. The rhamnofolane and daphnane skeletons are closely related, being formally derived from casbane by two cyclizations (6,10 and 5,14) followed by cleavage of the 1,15 (daphnane) or 2,15 (rhamnofolane) cyclopropane bonds.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassDiterpenoids
Direct ParentRhamnofolane and daphnane diterpenoids
Alternative Parents
Substituents
  • Daphnane diterpenoid
  • Methoxyphenol
  • Phenoxy compound
  • Anisole
  • Methoxybenzene
  • Phenol ether
  • 1-hydroxy-2-unsubstituted benzenoid
  • 1,3-dioxepane
  • Alkyl aryl ether
  • Carboxylic acid orthoester
  • Dioxepane
  • Phenol
  • Ortho ester
  • Meta-dioxane
  • Monocyclic benzene moiety
  • Benzenoid
  • Tertiary alcohol
  • Meta-dioxolane
  • Ketone
  • Carboxylic acid ester
  • Orthocarboxylic acid derivative
  • Ether
  • Organoheterocyclic compound
  • Oxacycle
  • Carboxylic acid derivative
  • Monocarboxylic acid or derivatives
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Alcohol
  • Organic oxygen compound
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Actin Cytoskeleton
  • Actin Filament
  • Apical Membrane
  • Basolateral Membrane
  • Cell surface
  • Cytosol
  • Endoplasmic reticulum
  • Extracellular
  • Lysosome
  • Membrane
  • Microtubule
  • Mitochondrion
  • Nerve Fiber
  • Nuclear Membrane
  • Perinuclear region
  • Plasma Membrane
  • Sarcoplasmic Reticulum
  • Soluble Fraction
  • Synaptic Vesicle
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
Cell cycleNot Availablemap04110
Long-term potentiationNot Availablemap04720
Insulin secretionNot Availablemap04911
Gastric acid secretionNot Availablemap04971
EndocytosisNot Availablemap04144
EicosanoidsNot 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
Water Solubility0.00082 g/LALOGPS
logP4.4ALOGPS
logP5.59ChemAxon
logS-5.9ALOGPS
pKa (Strongest Acidic)9.94ChemAxon
pKa (Strongest Basic)-3.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area120.75 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity170.1 m³·mol⁻¹ChemAxon
Polarizability67.25 ųChemAxon
Number of Rings7ChemAxon
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, Positivesplash10-004j-2500619000-0817b7af06ed27b3fa02View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00mk-3801911000-d7b6b333cbf2f8e70c1fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9300100000-82d92b6ae9cd1b229fb1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-01t9-0800109000-0574675e0f39362d5d87View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-0900202000-b64406249e41d53db444View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-044i-1900201000-b33ccb6e80de386b11f3View in MoNA
Toxicity Profile
Route of ExposureOral (ingestion) (2) ; dermal (2)
Mechanism of ToxicityResiniferatoxin activates the vanilloid receptor in a subpopulation of primary afferent sensory neurons involved in nociception (the transmission of physiological pain). RTX causes a novel ion channel in the plasma membrane of sensory neurons, the transient receptor potential vanilloid 1, to become permeable to cations, most particularly the calcium cation. This evokes a powerful irritant effect followed by desensitization and analgesia. (1)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesResiniferatoxin (RTX) is a plant toxin and ultrapotent capsaicin analog that occurs in various species of plants, such as resin spurge (Euphorbia resinifera). (1) Investigated for use/treatment in interstitial cystitis and urinary incontinence.
Minimum Risk LevelNot Available
Health EffectsResiniferatoxin is a neurotoxin that targets afferent sensory neurons involved in nociception. It evokes a powerful irritant effect followed by desensitization and analgesia. (1)
SymptomsResiniferatoxin evokes a powerful irritant effect followed by desensitization and analgesia. (1)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID104826
ChEMBL IDCHEMBL448382
ChemSpider ID94623
KEGG IDC09179
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDResiniferatoxin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkResiniferatoxin
References
Synthesis ReferenceNot Available
MSDST3D3084.pdf
General References
  1. Wikipedia. Resiniferatoxin. Last Updated 19 May 2009. [Link]
  2. Wikipedia. Phytotoxin. Last Updated 7 August 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Transmembrane signaling receptor activity
Specific Function:
Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis (By similarity). Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel.
Gene Name:
TRPV1
Uniprot ID:
Q8NER1
Molecular Weight:
94955.33 Da
References
  1. Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, Moriello AS, Davis JB, Mechoulam R, Di Marzo V: Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 2001 Oct;134(4):845-52. [11606325 ]
  2. Wikipedia. Resiniferatoxin. Last Updated 19 May 2009. [Link]