Resiniferatoxin

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Resiniferatoxin
Accession Number
DB06515
Type
Small Molecule
Groups
Investigational
Description

Resiniferatoxin (RTX) is a naturally occurring, ultrapotent capsaicin analog that activates the vanilloid receptor in a subpopulation of primary afferent sensory neurons involved in nociception (the transmission of physiological pain).

Structure
Thumb
Synonyms
  • RTX
Categories
UNII
A5O6P1UL4I
CAS number
57444-62-9
Weight
Average: 628.7081
Monoisotopic: 628.267232878
Chemical Formula
C37H40O9
InChI Key
DSDNAKHZNJAGHN-IHCAYWNCSA-N
InChI
InChI=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
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
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

Pharmacology

Indication

Investigated for use/treatment in interstitial cystitis and urinary incontinence.

Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UTransient receptor potential cation channel subfamily V member 1Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Szallasi A, Blumberg PM: Resiniferatoxin, a phorbol-related diterpene, acts as an ultrapotent analog of capsaicin, the irritant constituent in red pepper. Neuroscience. 1989;30(2):515-20. [PubMed:2747924]
External Links
PubChem Compound
104826
ChemSpider
94623
BindingDB
20285
Wikipedia
Resiniferatoxin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingTreatmentIntractable Cancer Pain / Intractable Cancer-related Pain1
1RecruitingTreatmentKnee Osteoarthritis (Knee OA) / Pain, Knee1
1, 2RecruitingTreatmentNeoplasms Metastasis / Pain, Intractable / Palliative Care / Questionnaires & Amp; Surveys / Questionnaires &Amp; Surveys1
2Active Not RecruitingTreatmentGlomerulonephritis minimal lesion / Renal Insufficiency,Chronic1
2RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Malignant Neoplasm of Stomach1
2WithdrawnTreatmentGranulomatous and Lymphocytic Interstitial Lung Disease1
2, 3RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)2
4CompletedTreatmentRheumatoid Arthritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00082 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity170.1 m3·mol-1ChemAxon
Polarizability67.25 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8464
Blood Brain Barrier+0.599
Caco-2 permeable-0.6017
P-glycoprotein substrateSubstrate0.8899
P-glycoprotein inhibitor IInhibitor0.7963
P-glycoprotein inhibitor IINon-inhibitor0.5276
Renal organic cation transporterNon-inhibitor0.8185
CYP450 2C9 substrateNon-substrate0.859
CYP450 2D6 substrateNon-substrate0.8467
CYP450 3A4 substrateSubstrate0.7345
CYP450 1A2 substrateNon-inhibitor0.6836
CYP450 2C9 inhibitorNon-inhibitor0.7855
CYP450 2D6 inhibitorNon-inhibitor0.9175
CYP450 2C19 inhibitorNon-inhibitor0.7399
CYP450 3A4 inhibitorInhibitor0.5918
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7577
Ames testNon AMES toxic0.6839
CarcinogenicityNon-carcinogens0.9378
BiodegradationNot ready biodegradable0.9962
Rat acute toxicity3.9178 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9381
hERG inhibition (predictor II)Non-inhibitor0.6859
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound 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.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Diterpenoids
Direct Parent
Rhamnofolane and daphnane diterpenoids
Alternative Parents
Methoxyphenols / Phenoxy compounds / Methoxybenzenes / Anisoles / Ortho esters / 1,3-dioxepanes / 1-hydroxy-2-unsubstituted benzenoids / Alkyl aryl ethers / Carboxylic acid orthoesters / 1,3-dioxanes
show 8 more
Substituents
Daphnane diterpenoid / Methoxyphenol / Phenoxy compound / Anisole / Methoxybenzene / Phenol ether / 1-hydroxy-2-unsubstituted benzenoid / 1,3-dioxepane / Alkyl aryl ether / Carboxylic acid orthoester
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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 aci...
Gene Name
TRPV1
Uniprot ID
Q8NER1
Uniprot Name
Transient receptor potential cation channel subfamily V member 1
Molecular Weight
94955.33 Da
References
  1. Szallasi A, Blumberg PM: Resiniferatoxin and its analogs provide novel insights into the pharmacology of the vanilloid (capsaicin) receptor. Life Sci. 1990;47(16):1399-408. [PubMed:2174484]
  2. Szallasi A, Conte B, Goso C, Blumberg PM, Manzini S: Characterization of a peripheral vanilloid (capsaicin) receptor in the urinary bladder of the rat. Life Sci. 1993;52(20):PL221-6. [PubMed:8483387]
  3. Nishihara K, Nozawa Y, Nakano M, Ajioka H, Matsuura N: Sensitizing effects of lafutidine on CGRP-containing afferent nerves in the rat stomach. Br J Pharmacol. 2002 Mar;135(6):1487-94. [PubMed:11906962]

Drug created on March 19, 2008 10:35 / Updated on November 02, 2018 06:17