Mestranol (T3D4791)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (6)XML
Targets (6)
Record Information
Version2.0
Creation Date2014-09-11 05:16:50 UTC
Update Date2014-12-24 20:26:57 UTC
Accession NumberT3D4791
Identification
Common NameMestranol
ClassSmall Molecule
DescriptionThe 3-methyl ether of ethinyl estradiol. It must be demethylated to be biologically active. It is used as the estrogen component of many combination ORAL contraceptives.
Compound Type
  • Drug
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(17a)-3-Methoxy-19-norpregna-1,3,5(10)-trien-20-yn-17-ol
(17b)-17-ethynyl-3-methoxyestra-1,3,5(10)-trien-17-ol
(17β)-17-Ethynyl-3-methoxyestra-1(10),2,4-trien-17-ol
(1S,10R,11S,14R,15S)-14-ethynyl-5-methoxy-15-methyltetracyclo[8.7.0.02,7.011,15]heptadeca-2(7),3,5-trien-14-ol
(8R,9S,13S,14S,17R)-17-Ethinyl-3-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-ol
(8R,9S,13S,14S,17R)-17-ethynyl-3-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-ol
(8S,9S,13S,14S,17S)-17-ethynyl-3-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-ol
17-Ethynyl-3-methoxy-1,3,5(10)-oestratien-17-β-ol
17-Ethynylestradiol 3-methyl ether
17a-Ethynyl-1,3,5(10)-estratriene-3,17b-diol 3-methyl ether
17a-Ethynyl-3-methoxy-1,3,5(10)-estratrien-17b-ol
17a-Ethynylestradiol 3-Methyl Ether
3-Methoxy-19-nor-17α-pregna-1,3,5(10)-trien-20-yn-17-ol
Chemical FormulaC21H26O2
Average Molecular Mass310.430 g/mol
Monoisotopic Mass310.193 g/mol
CAS Registry Number72-33-3
IUPAC Name(1S,10R,11S,14R,15S)-14-ethynyl-5-methoxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-14-ol
Traditional Name(1S,10R,11S,14R,15S)-14-ethynyl-5-methoxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-14-ol
SMILES[H][C@]12CC[C@](O)(C#C)[C@]1(C)CC[C@@]1([H])C3=CC=C(OC)C=C3CC[C@]21[H]
InChI IdentifierInChI=1/C21H26O2/c1-4-21(22)12-10-19-18-7-5-14-13-15(23-3)6-8-16(14)17(18)9-11-20(19,21)2/h1,6,8,13,17-19,22H,5,7,9-12H2,2-3H3/t17-,18-,19+,20+,21+/s2
InChI KeyInChIKey=IMSSROKUHAOUJS-ZTUUXWJNNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as estrane steroids. These are steroids with a structure based on the estrane skeleton.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassEstrane steroids
Direct ParentEstrane steroids
Alternative Parents
Substituents
  • Estrane-skeleton
  • Hydroxysteroid
  • 17-hydroxysteroid
  • Phenanthrene
  • Tetralin
  • Anisole
  • Alkyl aryl ether
  • Ynone
  • Benzenoid
  • Tertiary alcohol
  • Cyclic alcohol
  • Acetylide
  • Ether
  • Hydrocarbon derivative
  • Alcohol
  • Organooxygen compound
  • Organic oxygen compound
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • 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 Point150.5°C
Boiling PointNot Available
Solubility3.77e-03 g/L
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0038 g/LALOGPS
logP3.89ALOGPS
logP4.04ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)17.59ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.46 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity91.86 m³·mol⁻¹ChemAxon
Polarizability36.7 ųChemAxon
Number of Rings4ChemAxon
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, Positivesplash10-008i-0790000000-4f67d1073f5d63b0e27d2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0g4l-3559000000-e7deac0497bd25eac9e32017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0149000000-c1a392ac6a255cba0e082017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03dr-0592000000-0cc5cea78731703ef0b32017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0k9f-3980000000-fe6e57c0238f233c2ba62017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0009000000-85dc48ac6fb3820afe062017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0069000000-cd914e79f9bb96f842c32017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0f76-0090000000-84d635c97eb379340fca2017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0029000000-cb3f205cf264d3c6ade02021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00ko-0970000000-461534673e7c6e28a3982021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-072i-1940000000-132bc2499590ddce96ec2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0009000000-d834b990dbff0e00d2662021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0049000000-cca49518a1592cc727822021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0udi-0090000000-041fe496acbbddb615b12021-10-11View Spectrum
MSMass Spectrum (Electron Ionization)splash10-01t9-1972000000-5e394201ba0e38e5391f2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 25.16 MHz, CDCl3, experimental)Not Available2014-09-23View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityMestranol is the 3-methyl ether of ethinylestradiol. Ethinylestradiol, is a synthetic derivative of estradiol. Ethinylestradiol is orally bio-active and the estrogen used in almost all modern formulations of combined oral contraceptive pills. It binds to (and activates) the estrogen receptor. Mestranol is a biologically inactive prodrug of ethinylestradiol to which it is demethylated in the liver with a conversion efficiency of 70%. Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesMestranol was used as one of the first oral contraceptives.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01357
HMDB IDHMDB15446
PubChem Compound ID6291
ChEMBL IDCHEMBL1201151
ChemSpider ID6054
KEGG IDC07618
UniProt IDNot Available
OMIM ID
ChEBI ID6784
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkMestranol
References
Synthesis ReferenceNot Available
MSDST3D4791.pdf
General ReferencesNot Available
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
AC500.00519 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC500.0733 uMATG_ERa_TRANSAttagene
AC500.091 uMATG_ERE_CISAttagene
AC500.0229 uMNVS_NR_hERNovascreen
AC504.54 uMOT_ER_ERaERa_0480Odyssey Thera
AC501.75 uMOT_ER_ERaERa_1440Odyssey Thera
AC500.1 uMOT_ERa_EREGFP_0120Odyssey Thera
AC500.106 uMOT_ERa_EREGFP_0480Odyssey Thera
AC500.0515 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
AC500.00114 uMTox21_ERa_LUC_BG1_AgonistTox21/NCGC
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. Androgen receptor
General Function:
Zinc ion binding
Specific Function:
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.346 uMNVS_NR_hARNovascreen
AC502.79 uMTox21_AR_BLA_Antagonist_ratioTox21/NCGC
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. Retinoic acid receptor beta
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function.
Gene Name:
RARB
Uniprot ID:
P10826
Molecular Weight:
50488.63 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.721 uMATG_RARb_TRANSAttagene
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
4. Estrogen receptor beta
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
Gene Name:
ESR2
Uniprot ID:
Q92731
Molecular Weight:
59215.765 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501 uMOT_ER_ERaERb_0480Odyssey Thera
AC501.93 uMOT_ER_ERaERb_1440Odyssey Thera
AC504.2 uMOT_ER_ERbERb_0480Odyssey Thera
AC503.17 uMOT_ER_ERbERb_1440Odyssey Thera
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
5. Hepatocyte nuclear factor 4-alpha
General Function:
Zinc ion binding
Specific Function:
Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.
Gene Name:
HNF4A
Uniprot ID:
P41235
Molecular Weight:
52784.205 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.39 uMATG_HNF4a_TRANSAttagene
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
6. 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
AC505.99 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 ]