Estradiol (T3D4668)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (8)XML
Targets (8)
Record Information
Version2.0
Creation Date2014-09-11 02:03:56 UTC
Update Date2014-12-24 20:26:54 UTC
Accession NumberT3D4668
Identification
Common NameEstradiol
ClassSmall Molecule
DescriptionGenerally refers to the 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. In humans, it is produced primarily by the cyclic ovaries and the placenta. It is also produced by the adipose tissue of men and postmenopausal women. The 17-alpha-isomer of estradiol binds weakly to estrogen receptors (receptors, estrogen) and exhibits little estrogenic activity in estrogen-responsive tissues. Various isomers can be synthesized.
Compound Type
  • Animal Toxin
  • Anti-Menopausal Agent
  • Contraceptive Agent
  • Drug
  • Estrogen
  • Food Toxin
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(17beta)-Estra-1,3,5(10)-triene-3,17-diol
17beta Oestradiol
17beta-Estra-1,3,5(10)-triene-3,17-diol
17beta-Oestradiol
Alora
Benzhormovarine
beta-Estradiol
cis-Estradiol
Climara
Depo-Estradiol
Dihydrofollicular hormone
Dihydrofolliculin
Dihydrotheelin
Dihydroxyestrin
Divigel
Elestrin
Estrace
Estraderm MX
Estraderm TTS
Estradiol-17beta
Estradiolum
Estrasorb
Estring
Estrofem
Estrogel
EvaMist
Femestral
Femring
Femtrace
Innofem
Lio-Oid
Menostar
Minivelle
Vagifem
Vivelle
Vivelle-Dot
Chemical FormulaC18H24O2
Average Molecular Mass272.382 g/mol
Monoisotopic Mass272.178 g/mol
CAS Registry Number50-28-2
IUPAC Name(1S,10R,11S,14S,15S)-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-triene-5,14-diol
Traditional Name(1S,10R,11S,14S,15S)-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-triene-5,14-diol
SMILES[H][C@]1(O)CC[C@@]2([H])[C@]3([H])CCC4=CC(O)=CC=C4[C@@]3([H])CC[C@]12C
InChI IdentifierInChI=1S/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-17,19-20H,2,4,6-9H2,1H3/t14-,15-,16+,17+,18+/m1/s1
InChI KeyInChIKey=VOXZDWNPVJITMN-ZBRFXRBCSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassEstrane steroids
Direct ParentEstrogens and derivatives
Alternative Parents
Substituents
  • Estrogen-skeleton
  • 17-hydroxysteroid
  • Hydroxysteroid
  • 3-hydroxysteroid
  • Phenanthrene
  • Tetralin
  • 1-hydroxy-2-unsubstituted benzenoid
  • Benzenoid
  • Cyclic alcohol
  • Secondary alcohol
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Alcohol
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
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 Point151-152°C
Boiling PointNot Available
Solubility3.6 mg/L (at 27°C)
LogP4.01
Predicted Properties
PropertyValueSource
Water Solubility0.021 g/LALOGPS
logP3.57ALOGPS
logP3.75ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)10.33ChemAxon
pKa (Strongest Basic)-0.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity79.9 m³·mol⁻¹ChemAxon
Polarizability32.12 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-017r-1791100000-7b16254894cdcb8ee86d2014-06-16View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-1980000000-b2dec84718861de189ec2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-3940000000-f3692a81f624f15d3e0b2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-0960000000-be4e96105398cb805cd92017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-0790000000-5c858378c151358118242017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-017r-1791100000-7b16254894cdcb8ee86d2017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-052f-1490000000-9f16d080d50dcea52de42017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0udr-2279400000-cea6d26f1ab9c44b51602017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-05fr-0590000000-1dd83cbcb3d21edfbdbd2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0a4i-2900000000-f3279d6cdab9cf3800fd2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0a4i-8900000000-0efe28378f612aab8c3d2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (JEOL JMS-01-SG-2) , Positivesplash10-00di-1980000000-b2dec84718861de189ec2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI RMU-6E) , Positivesplash10-00di-3940000000-f3692a81f624f15d3e0b2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-52) , Positivesplash10-00di-0960000000-be4e96105398cb805cd92012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80) , Positivesplash10-00di-0790000000-5c83456da6e28375ad512012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-00di-0490000000-c3c4658cfae36bedff302017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-1900000000-51d28e077b0aefa6aa1c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-2900000000-a22a9233ffbb9eb05a1b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-0960000000-d2ee002f4c0363c04e832017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-0960000000-2ad7c6e17386448419df2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-00di-0090000000-f73a7a19d55a4f78be012021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 80V, Positivesplash10-0a4i-2900000000-a22a9233ffbb9eb05a1b2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 55V, Positivesplash10-0a4i-1900000000-51d28e077b0aefa6aa1c2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-002b-0930000000-c177eb564c729479f2be2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0a4i-0190000000-b572b380a16bb1b20b272021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0002-0960000000-d2ee002f4c0363c04e832021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Negativesplash10-00di-0090000000-f906ca4989738e61667a2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0ab9-0190000000-2924fb687c668eb8918a2017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0ab9-0590000000-53eccf4b813f6992d38d2017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-6890000000-c399a267a752cfdba3232017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0090000000-274ccc6305612709fd332017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0090000000-afc94cc62691bfb341612017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-054o-0190000000-8d49a19142b1bd1a09a12017-07-26View Spectrum
MSMass Spectrum (Electron Ionization)splash10-075a-2920000000-10218bfa5b56f829853e2014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, 100%_DMSO, experimental)Not Available2012-12-04View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, 100%_DMSO, experimental)Not Available2012-12-04View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityEstradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. 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.
MetabolismExogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estrogens are partially metabolized by cytochrome P450. Route of Elimination: Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates. Half Life: 36 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of urogenital symptoms associated with post-menopausal atrophy of the vagina (such as dryness, burning, pruritus and dyspareunia) and/or the lower urinary tract (urinary urgency and dysuria).
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsCan cause nausea and vomiting, and withdrawal bleeding may occur in females.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00783
HMDB IDNot Available
PubChem Compound ID5757
ChEMBL IDCHEMBL135
ChemSpider ID5554
KEGG IDC00951
UniProt IDNot Available
OMIM ID
ChEBI ID16469
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkEstradiol
References
Synthesis Reference

Akira Nakagawa, Munehiko Hirano, Miyuki Shinmura, “Estradiol percutaneous administration preparations.” U.S. Patent US5248676, issued November, 1980.

MSDST3D4668.pdf
General References
  1. Pentikainen V, Erkkila K, Suomalainen L, Parvinen M, Dunkel L: Estradiol acts as a germ cell survival factor in the human testis in vitro. J Clin Endocrinol Metab. 2000 May;85(5):2057-67. [10843196 ]
  2. Sharpe RM, Skakkebaek NE: Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet. 1993 May 29;341(8857):1392-5. [8098802 ]
  3. Raman JD, Schlegel PN: Aromatase inhibitors for male infertility. J Urol. 2002 Feb;167(2 Pt 1):624-9. [11792932 ]
  4. Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, Korach KS, Simpson ER: Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med. 1997 Jul 10;337(2):91-5. [9211678 ]
  5. Behl C, Widmann M, Trapp T, Holsboer F: 17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem Biophys Res Commun. 1995 Nov 13;216(2):473-82. [7488136 ]
  6. Schmidt JW, Wollner D, Curcio J, Riedlinger J, Kim LS: Hormone replacement therapy in menopausal women: Past problems and future possibilities. Gynecol Endocrinol. 2006 Oct;22(10):564-77. [17135036 ]
  7. Foresta C, Zuccarello D, Biagioli A, De Toni L, Prana E, Nicoletti V, Ambrosini G, Ferlin A: Oestrogen stimulates endothelial progenitor cells via oestrogen receptor-alpha. Clin Endocrinol (Oxf). 2007 Oct;67(4):520-5. Epub 2007 Jun 15. [17573901 ]
  8. Garcia-Segura LM, Sanz A, Mendez P: Cross-talk between IGF-I and estradiol in the brain: focus on neuroprotection. Neuroendocrinology. 2006;84(4):275-9. Epub 2006 Nov 23. [17124377 ]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

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
AC500.00338 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC500.091 uMATG_ERa_TRANSAttagene
AC500.091 uMATG_ERE_CISAttagene
AC500.0229 uMNVS_NR_hERNovascreen
AC500.0612 uMOT_ER_ERaERa_0480Odyssey Thera
AC500.0569 uMOT_ER_ERaERa_1440Odyssey Thera
AC500.001 uMOT_ERa_EREGFP_0120Odyssey Thera
AC500.00204 uMOT_ERa_EREGFP_0480Odyssey Thera
AC500.000335 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
AC500.000589 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
AC500.00293 uMNVS_NR_hARNovascreen
AC500.393 uMOT_AR_ARSRC1_0480Odyssey Thera
AC500.219 uMOT_AR_ARSRC1_0960Odyssey Thera
AC501.14 uMTox21_AR_BLA_Agonist_ratioTox21/NCGC
AC500.559 uMTox21_AR_LUC_MDAKB2_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
3. 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
AC500.0316 uMOT_ER_ERaERb_0480Odyssey Thera
AC500.0296 uMOT_ER_ERaERb_1440Odyssey Thera
AC500.0132 uMOT_ER_ERbERb_0480Odyssey Thera
AC500.0101 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
4. Sodium-dependent dopamine transporter
General Function:
Monoamine transmembrane transporter activity
Specific Function:
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A3
Uniprot ID:
Q01959
Molecular Weight:
68494.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.106 uMNVS_TR_hDATNovascreen
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. Progesterone receptor
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
AC500.124 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 ]
Target Details
6. Glucocorticoid receptor
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
AC501.12 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 ]
Target Details
7. 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
AC508.96 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 ]
Target Details
8. Cytochrome P450 2C18
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP2C18
Uniprot ID:
P33260
Molecular Weight:
55710.075 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC509.42 uMNVS_ADME_hCYP2C18Novascreen
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 ]