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Record Information
Version2.0
Creation Date2014-09-11 02:05:13 UTC
Update Date2014-12-24 20:26:55 UTC
Accession NumberT3D4693
Identification
Common NameEquilin
ClassSmall Molecule
DescriptionAn estrogenic steroid produced by horses. It has a total of four double bonds in the A- and B-ring. High concentration of euilin is found in the urine of pregnant mares. Equilin is one of the estrogens present in the mixture of estrogens isolated from horse urine and marketed as Premarin. Premarin became the most commonly used form of estrogen for hormone replacement therapy in the United States of America. Estrone is the major estrogen in Premarin (about 50%) and equilin is present as about 25% of the total. Estrone is a major estrogen that is normally found in women. Equilin is not normally present in women, so there has been interest in the effects of equilin on the human body. The estrogens in Premarin are present mainly as "conjugates", modified chemical forms in which the active estrogen is coupled to another chemical group such as sulfate. Estrone sulfate is usually the major form of estrogen in women. After being taken into a woman's body, the conjugated estrogens of Premarin are converted to the active unconjugated estrogens or excreted from the woman's body. Estrone can be converted to estradiol, which is thought to be the major active estrogen in women.
Compound Type
  • Drug
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1,3,5,7-Estratetraen-3-ol-17-one
7-Dehydroestrone
Dihydroequilenin
Chemical FormulaC18H20O2
Average Molecular Mass268.350 g/mol
Monoisotopic Mass268.146 g/mol
CAS Registry Number474-86-2
IUPAC Name(1S,11S,15S)-5-hydroxy-15-methyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-2(7),3,5,9-tetraen-14-one
Traditional Nameequilin
SMILES[H][C@@]12CCC(=O)[C@@]1(C)CC[C@]1([H])C3=CC=C(O)C=C3CC=C21
InChI IdentifierInChI=1S/C18H20O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3-5,10,14,16,19H,2,6-9H2,1H3/t14-,16+,18+/m1/s1
InChI KeyInChIKey=WKRLQDKEXYKHJB-HFTRVMKXSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as oxosteroids. These are steroid derivatives carrying a C=O group attached to steroid skeleton.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassOxosteroids
Direct ParentOxosteroids
Alternative Parents
Substituents
  • 3-hydroxy-delta-7-steroid
  • 3-hydroxysteroid
  • Hydroxysteroid
  • Oxosteroid
  • 17-oxosteroid
  • Delta-7-steroid
  • Phenanthrene
  • Naphthalene
  • 1-hydroxy-2-unsubstituted benzenoid
  • Benzenoid
  • Ketone
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Carbonyl group
  • Organic oxide
  • Organooxygen compound
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
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 Point239°C
Boiling PointNot Available
Solubility1.41 mg/L (at 25°C)
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.013 g/LALOGPS
logP3.8ALOGPS
logP3.9ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)9.41ChemAxon
pKa (Strongest Basic)-6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity79.93 m³·mol⁻¹ChemAxon
Polarizability30.55 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0090000000-cde4cdd88f0562fdc5a52016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-0390000000-1a607d6e0d7b532ef4182016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ufr-8890000000-ccbc5fcb66a5cec1bcd12016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0090000000-9400bec1ff62b5bce1a82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0090000000-3987374448266c42e9d62016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0f79-1190000000-ffc0bb50ee42b6c9f8d72016-08-03View Spectrum
MSMass Spectrum (Electron Ionization)splash10-014i-3940000000-b80393e552aa786000702014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 50.18 MHz, CDCl3, experimental)Not Available2014-09-23View Spectrum
Toxicity Profile
Route of ExposureWell absorbed.
Mechanism of ToxicityEstrogens enter the cells of responsive tissues (e.g., female organs, breasts, hypothalamus, pituitary) where they interact with a protein receptor, subsequently increasing the rate of synthesis of DNA, RNA, and some proteins. Estrogens decrease the secretion of gonadotropin-releasing hormone by the hypothalamus, reducing the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary.
MetabolismHepatic.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of moderate to severe vasomotor symptoms associated with the menopause, atrophic vaginitis, osteoporosis, hypoestrogenism due to hypogonadism, castration, primary ovarian failure, breast cancer (for palliation only), and Advanced androgen-dependent carcinoma of the prostate (for palliation only)
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB02187
HMDB IDNot Available
PubChem Compound ID223368
ChEMBL IDCHEMBL323533
ChemSpider ID193995
KEGG IDC14392
UniProt IDNot Available
OMIM ID
ChEBI ID42309
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkEquilin
References
Synthesis ReferenceNot Available
MSDST3D4693.pdf
General References
  1. Sawicki MW, Erman M, Puranen T, Vihko P, Ghosh D: Structure of the ternary complex of human 17beta-hydroxysteroid dehydrogenase type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin) and NADP+. Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):840-5. [9927655 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Testosterone dehydrogenase (nad+) activity
Specific Function:
Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
Gene Name:
HSD17B1
Uniprot ID:
P14061
Molecular Weight:
34949.715 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
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
AC500.00203 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC500.0417 uMATG_ERa_TRANSAttagene
AC500.0629 uMATG_ERE_CISAttagene
AC500.00763 uMNVS_NR_hERNovascreen
AC500.338 uMOT_ER_ERaERa_0480Odyssey Thera
AC500.1 uMOT_ER_ERaERa_1440Odyssey Thera
AC500.3 uMOT_ERa_EREGFP_0120Odyssey Thera
AC500.1 uMOT_ERa_EREGFP_0480Odyssey Thera
AC500.00556 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
AC500.00118 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 ]
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
AC500.0461 uMNVS_NR_hARNovascreen
AC501.21 uMOT_AR_ARSRC1_0480Odyssey Thera
AC501.68 uMOT_AR_ARSRC1_0960Odyssey Thera
AC507.42 uMTox21_AR_BLA_Antagonist_ratioTox21/NCGC
AC504.68 uMTox21_AR_LUC_MDAKB2_AgonistTox21/NCGC
AC508.74 uMTox21_AR_LUC_MDAKB2_AntagonistTox21/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 ]
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
AC500.1 uMOT_ER_ERaERb_0480Odyssey Thera
AC500.1 uMOT_ER_ERaERb_1440Odyssey Thera
AC500.117 uMOT_ER_ERbERb_0480Odyssey Thera
AC500.1 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 ]
General Function:
Zinc ion binding
Specific Function:
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
Gene Name:
PGR
Uniprot ID:
P06401
Molecular Weight:
98979.96 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.122 uMNVS_NR_hPRNovascreen
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 ]
General Function:
Zinc ion binding
Specific Function:
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
Gene Name:
NR3C1
Uniprot ID:
P04150
Molecular Weight:
85658.57 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.55 uMTox21_GR_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 ]