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Record Information
Version2.0
Creation Date2014-08-29 05:02:19 UTC
Update Date2014-12-24 20:26:37 UTC
Accession NumberT3D4069
Identification
Common NamePhorbol
ClassSmall Molecule
DescriptionPhorbol is a natural, plant-derived organic compound. It is a member of the tigliane family of diterpenes. Phorbol was first isolated in 1934 as the hydrolysis product of croton oil, which is derived from the seeds of the purging croton, Croton tiglium. The structure of phorbol was determined in 1967. It is very soluble in most polar organic solvents, as well as in water.
Compound Type
  • Ester
  • Industrial/Workplace Toxin
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
Synonyms
Synonym
4,9,12beta,13,20-Pentahydroxy-1,6-tigliadien-3-on
4,9,12beta,13,20-Pentahydroxytiglia-1,6-dien-3-one
Chemical FormulaC20H28O6
Average Molecular Mass364.433 g/mol
Monoisotopic Mass364.189 g/mol
CAS Registry Number17673-25-5
IUPAC Name(1S,2S,6R,10S,11R,13S,14R,15R)-1,6,13,14-tetrahydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyltetracyclo[8.5.0.0²,⁶.0¹¹,¹³]pentadeca-3,8-dien-5-one
Traditional Namephorbol
SMILES[H][C@]12[C@]3([H])C=C(CO)C[C@]4(O)C(=O)C(C)=C[C@@]4([H])[C@@]3(O)[C@]([H])(C)[C@@]([H])(O)[C@@]1(O)C2(C)C
InChI IdentifierInChI=1S/C20H28O6/c1-9-5-13-18(24,15(9)22)7-11(8-21)6-12-14-17(3,4)20(14,26)16(23)10(2)19(12,13)25/h5-6,10,12-14,16,21,23-26H,7-8H2,1-4H3/t10-,12+,13-,14-,16-,18-,19-,20-/m1/s1
InChI KeyInChIKey=QGVLYPPODPLXMB-UBTYZVCOSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as tigliane and ingenane diterpenoids. These are diterpenoids containing the tigliane or ingenane carbon skeleton. The tigliane skeleton is a tetracyclic ring that consists of the 4/7/6/3 ring junction. It is derived from casbane by 6,10- and 5,14-cyclizations and is a framework of phorbol. The ingenane skeleton is derived by rearrangement of tigliane.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassDiterpenoids
Direct ParentTigliane and ingenane diterpenoids
Alternative Parents
Substituents
  • Tigliane diterpenoid
  • Tertiary alcohol
  • Cyclic alcohol
  • Secondary alcohol
  • Ketone
  • Cyclopropanol
  • Polyol
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Actin Cytoskeleton
  • Actin Filament
  • Apical Membrane
  • Basolateral Membrane
  • Caveolae
  • Cell junction
  • Cell surface
  • Cytoplasm
  • Cytoplasmic vesicle
  • Cytoskeleton
  • Cytosol
  • Early endosome
  • Endocytic Vesicle
  • Endoplasmic reticulum
  • Endosome
  • Extracellular
  • Extracellular matrix
  • Focal adhesion
  • Golgi apparatus
  • Lysosome
  • Membrane Fraction
  • Microsome
  • Microtubule
  • Mitochondrial Matrix
  • Mitochondrion
  • Nuclear Membrane
  • Nucleolus
  • Perinuclear region
  • Plasma Membrane
  • Ribosome
  • Sarcoplasmic Reticulum
  • Secretory vesicle
  • Soluble Fraction
  • Synaptic Vesicle
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
EndocytosisNot Availablemap04144
Cell cycleNot Availablemap04110
Insulin secretionNot Availablemap04911
Arachidonic Acid MetabolismSMP00075 map00590
Fatty acid MetabolismSMP00051 map00071
MelanogenesisNot Availablemap04916
Long-term potentiationNot Availablemap04720
PhenothiazinesNot AvailableNot Available
Dna replicationNot Availablemap03030
PhototransductionNot Availablemap04744
Nucleotide Excision RepairSMP00478 map03420
Metabolic PathwaysNot AvailableNot Available
Ether lipid metabolismNot Availablemap00565
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point250-251°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility4.16 g/LALOGPS
logP0.31ALOGPS
logP-0.78ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)12.48ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area118.22 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity95.78 m³·mol⁻¹ChemAxon
Polarizability38.93 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-002b-0009000000-7604808bfe64b4118626JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004j-0019000000-65cd879dac531cb9a0f9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004r-4189000000-e1dc74e128977ff2061cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0009000000-96890c20944391c9f1cfJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01ot-0009000000-f33908124bd1423bbe35JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00c0-4903000000-379adb0ac7e3ac2801fcJSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityThe term 'phorbol' is used to describe the family of naturally occurring compounds that can be referred to as tigliane diterpenes. Phorbol esters are the tetracyclic diterpenoids generally known for their tumor promoting activity. The phorbol esters mimic the action of diacyl glycerol (DAG), activator of protein kinase C, which regulates different signal transduction pathways and other cellular metabolic activities. The biological activities of the phorbol esters are highly structure specific. The phorbol esters, even at very low concentrations, show toxicological manifestations in animals fed diets containing them. This toxicity limits the use of many nutritive plants and agricultural by-products containing phorbol esters to be used as animal feed. Besides, possessing antinutritional and toxic effects, few derivatives of the phorbol esters are also known for their antimicrobial and antitumor activities. The molluscicidal and insecticidal properties of phorbol esters indicate its potential to be used as an effective biopesticide and insecticide. The phorbols themselves do not induce tumors but promote tumor growth following exposure to a subcarcinogenic dose of a carcinogen. TPA and related phorbols were reported to be a potent stimulator for plasminogen activator synthesis. A good correlation was observed between plasminogen activator induction and tumor promotion with TPA, phorbol 12,13-didecanoate (PDD), and TPA beta-oxide (a derivative of TPA) in bioassays. The phorbol does not involve covalent binding to the cellular DNA, in fact it mimics the effects of transformation such as alteration in membrane morphology, increased saturation density, altered cell surface fucose glycopeptides, and increased the level of plasminogen activator and ornithine decarboxylase. (1) Various esters of phorbol have important biological properties, the most notable of which is the capacity to act as tumor promoters through activation of protein kinase C. They mimic diacylglycerols, glycerol derivatives in which two hydroxyl groups have reacted with fatty acids to form esters. The most common phorbol ester is 12-O-tetradecanoylphorbol-13-acetate (TPA), also called phorbol-12-myristate-13-acetate (PMA), which is used as a biomedical research tool in models of carcinogenesis. TPA, together with ionomycin, can also be used to stimulate T-cell activation, proliferation, and cytokine production, and is used in protocols for intracellular staining of these cytokines. (Wikipedia)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC.
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID442070
ChEMBL IDCHEMBL124518
ChemSpider ID390610
KEGG IDC09155
UniProt IDNot Available
OMIM ID
ChEBI IDCHEBI:8116
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkPhorbol
References
Synthesis ReferenceNot Available
MSDST3D4069.pdf
General References
  1. Goel G, Makkar HP, Francis G, Becker K: Phorbol esters: structure, biological activity, and toxicity in animals. Int J Toxicol. 2007 Jul-Aug;26(4):279-88. [17661218 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available