Enterolactone (T3D3967)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (3)XML
Targets (3)
Record Information
Version2.0
Creation Date2014-08-29 04:48:01 UTC
Update Date2014-12-24 20:26:35 UTC
Accession NumberT3D3967
Identification
Common NameEnterolactone
ClassSmall Molecule
DescriptionEnterolactone is a mammalian lignan that have a similar biphenolic structure to lignans from plants. Lignans are compounds with estrogenic properties and are probably the most important source of phytoestrogens in western diets. Mammalian lignans are formed from precursors that are contained mainly in vegetables, whole grain products and berries, via action of intestinal microflora. Enterolactone is produced in the colon by the action of bacteria on secoisolariciresinol, matairesinol and its glycosides. Secoisolariciresinol is converted to enterodiol which is subsequently converted to enterolactone as it passes through the colon. Matairesinol is converted directly to enterolactone. Enterolactone have been shown to possess weakly estrogenic and antiestrogenic activities, and it has been suggested that the high production of this antiestrogenic mammalian lignans in the gut may serve to protect against breast cancer in women and prostate cancer in men; however epidemiological evidence to date is conflicting. (1, 2, 3, 4).
Compound Type
  • Animal Toxin
  • Ester
  • Ether
  • Food Toxin
  • Industrial/Workplace Toxin
  • Mammal Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
2,3-Bis(3'-hydroxybenzyl)butyrolactone
3,4-Bis((3-hydroxyphenyl)methyl)dihydro-2-(3H)-furanone
Dihydro-3,4-bis((3-hydroxyphenyl)methyl)-2(3H)-Furanone
Chemical FormulaC18H18O4
Average Molecular Mass298.333 g/mol
Monoisotopic Mass298.121 g/mol
CAS Registry Number76543-15-2
IUPAC Name3,4-bis[(3-hydroxyphenyl)methyl]oxolan-2-one
Traditional NameHPMF
SMILESOC1=CC=CC(CC2COC(=O)C2CC2=CC(O)=CC=C2)=C1
InChI IdentifierInChI=1/C18H18O4/c19-15-5-1-3-12(8-15)7-14-11-22-18(21)17(14)10-13-4-2-6-16(20)9-13/h1-6,8-9,14,17,19-20H,7,10-11H2
InChI KeyInChIKey=HVDGDHBAMCBBLR-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dibenzylbutyrolactone lignans. These are lignan compounds containing a 3,4-dibenzyloxolan-2-one moiety.
KingdomOrganic compounds
Super ClassLignans, neolignans and related compounds
ClassFuranoid lignans
Sub ClassTetrahydrofuran lignans
Direct ParentDibenzylbutyrolactone lignans
Alternative Parents
Substituents
  • Dibenzylbutyrolactone
  • Lignan lactone
  • 1-hydroxy-4-unsubstituted benzenoid
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Monocyclic benzene moiety
  • Gamma butyrolactone
  • Benzenoid
  • Tetrahydrofuran
  • Carboxylic acid ester
  • Lactone
  • Carboxylic acid derivative
  • Oxacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organic oxide
  • Organic oxygen compound
  • Carbonyl group
  • Organooxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
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 Solubility0.022 g/LALOGPS
logP3.2ALOGPS
logP3.61ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)9.16ChemAxon
pKa (Strongest Basic)-6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area66.76 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity82.71 m³·mol⁻¹ChemAxon
Polarizability30.77 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-2930000000-324d2f99f3a80a9100172017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-004i-2936200000-90d0a08c212a572a564a2017-10-06View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0190000000-642d4c8d3404bc3f1f382016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a5a-0490000000-0fc8cabcfd095169a5272016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014l-4930000000-03f5b31277825fdc664c2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-c0857d2d2f364ae915602016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0f6t-0190000000-f43dcd7ff2ab06e61ff12016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014r-1950000000-316abee781de19a5a2ba2016-08-03View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesEnterolactone is produced in the colon by the action of bacteria on secoisolariciresinol, matairesinol and its glycosides.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB06101
PubChem Compound ID123917
ChEMBL IDCHEMBL465152
ChemSpider ID110448
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID562788
BioCyc ID2-CHLORO-TRANS-DIENELACTONE
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Boccardo F, Puntoni M, Guglielmini P, Rubagotti A: Enterolactone as a risk factor for breast cancer: a review of the published evidence. Clin Chim Acta. 2006 Mar;365(1-2):58-67. Epub 2005 Sep 15. [16168401 ]
  2. Wang LQ: Mammalian phytoestrogens: enterodiol and enterolactone. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Sep 25;777(1-2):289-309. [12270221 ]
  3. Adlercreut H, Mazur W, Stumpf K, Kilkkinen A, Pietinen P, Hulten K, Hallmans G: Food containing phytoestrogens, and breast cancer. Biofactors. 2000;12(1-4):89-93. [11216511 ]
  4. Adlercreutz H: Phyto-oestrogens and cancer. Lancet Oncol. 2002 Jun;3(6):364-73. [12107024 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Estrogen receptor
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.94 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC503.29 uMNVS_NR_hERNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
2. Translocator protein
General Function:
Cholesterol binding
Specific Function:
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
Gene Name:
TSPO
Uniprot ID:
P30536
Molecular Weight:
18827.81 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.88 uMNVS_MP_hPBRNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
3. Nuclear receptor subfamily 1 group I member 2
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.06 uMATG_PXR_TRANSAttagene
AC507.72 uMATG_PXRE_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]