Ethinyl Estradiol (T3D4743)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (17)XML
Targets (17)
Record Information
Version2.0
Creation Date2014-09-11 05:14:23 UTC
Update Date2014-12-24 20:26:56 UTC
Accession NumberT3D4743
Identification
Common NameEthinyl Estradiol
ClassSmall Molecule
DescriptionA semisynthetic alkylated estradiol with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally and is often used as the estrogenic component in oral contraceptives . Ethinyl estradiol is marketed mostly as a combination oral contraceptive under several brand names such as Alesse, Tri-Cyclen, Triphasil, and Yasmin. The FDA label includes a black box warning that states that combination oral contraceptives should not be used in women over 35 years old who smoke due to the increased risk of serious cardiovascular side effects.
Compound Type
  • Drug
  • Estrogen
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
17 alpha-Ethinylestradiol
17 alpha-Ethynylestradiol
17 alpha-Ethynyloestradiol
17-Ethinyl-3,17-estradiol
17-Ethinyl-3,17-oestradiol
17-Ethinylestradiol
17-Ethynylestradiol
17-Ethynylestradiol ram
17-Ethynyloestradiol
17a-Ethinyl-17b-estradiol
17a-Ethinylestradiol
17a-Ethynyl-17b-oestradiol
17a-Ethynylestradiol-l7b
17a-Ethynyloestradiol
17a-Ethynyloestradiol-17b
17alpha-Ethinyl estradiol
17α-ethynylestradiol
Alora
Amenoron
Anovlar
Chee-O-Gen
Chee-O-Genf
Diognat-E
Diogyn E
Diogyn-E
Dyloform
Ertonyl
Esclim
Esteed
Estigyn
Estinyl
Eston-E
Estoral
Estoral {[Orion]}
Estorals
Estring
Estrogen
Ethidol
Ethinoral
Ethinyl estradiol
Ethinyl-Oestranol
Ethinylestradiol
Ethinylestradiolum
Ethinylestriol
Ethinyloestradiol
Ethynyl estradiol
Ethynylestradiol
Ethynyloestradiol
Eticyclin
Eticyclol
Eticylol
Etinestrol
Etinestryl
Etinilestradiol
Etinoestryl
Etistradiol
Etivex
Feminone
Fempatch
Follicoral
Ginestrene
Gynodiol
Gynolett
Inestra
Innofem
Kolpolyn
Linoral
Lynoral
Menolyn
Menostar
Neo-Estrone
Nogest-S
Novestrol
Oradiol
Orestralyn
Orestrayln
Ovex
Palonyl
Perovex
Primogyn
Primogyn C
Primogyn M
Progynon C
Progynon M
Spanestrin
Thiuram E
Thiuranide
Vagifem
Ylestrol
Chemical FormulaC20H24O2
Average Molecular Mass296.403 g/mol
Monoisotopic Mass296.178 g/mol
CAS Registry Number57-63-6
IUPAC Name(1S,10R,11S,14R,15S)-14-ethynyl-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,14R,15S)-14-ethynyl-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-triene-5,14-diol
SMILES[H][C@]12CC[C@](O)(C#C)[C@]1(C)CC[C@@]1([H])C3=CC=C(O)C=C3CC[C@]21[H]
InChI IdentifierInChI=1/C20H24O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,5,7,12,16-18,21-22H,4,6,8-11H2,2H3/t16-,17-,18+,19+,20+/s2
InChI KeyInChIKey=BFPYWIDHMRZLRN-RHKZOZTBNA-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
  • 3-hydroxysteroid
  • Hydroxysteroid
  • 17-hydroxysteroid
  • Phenanthrene
  • Tetralin
  • 1-hydroxy-2-unsubstituted benzenoid
  • Benzenoid
  • Ynone
  • Cyclic alcohol
  • Tertiary alcohol
  • Acetylide
  • Organic oxygen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Alcohol
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Adrenal Cortex
  • Adrenal Gland
  • Bladder
  • Brain
  • Epidermis
  • Fibroblasts
  • Gonads
  • Intestine
  • Kidney
  • Liver
  • Muscle
  • Nerve Cells
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
  • Stratum Corneum
  • Testes
  • Thyroid Gland
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point142-144°C
Boiling PointNot Available
Solubility11.3 mg/L (at 27°C)
LogP3.67
Predicted Properties
PropertyValueSource
Water Solubility0.0068 g/LALOGPS
logP3.63ALOGPS
logP3.9ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)10.33ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity87.37 m³·mol⁻¹ChemAxon
Polarizability34.53 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 - EI-B (Non-derivatized)splash10-03di-0890000000-5219bc8ac1212313c9c02017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-03di-0890000000-5219bc8ac1212313c9c02018-05-18View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-06ec-0890000000-23c55dc07e698aa701e42017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-01t9-3264900000-27be1780fbc6934a75b02017-10-06View 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 (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000b-0290000000-0ef72fb5e00440b9ff502012-07-25View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-000i-0960000000-945d82a0ab94f246ac882012-07-25View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-056s-2910000000-0d38daebb87a39304e912012-07-25View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80) , Positivesplash10-03di-0890000000-7a166e952207cf7bc1d32012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0a4i-1790000000-194c2e946cdaab2072ce2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0190000000-075ad04641619da4b2f52017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004j-0390000000-70fa13954d5025b402ba2017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fbc-6980000000-8d3156c6218c2f54df342017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-6490bc65476d939667d62017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0090000000-9c8e8277a610eab839c82017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00p0-0090000000-87d77005eb0529ab1abb2017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0090000000-fb34058a34b84424b0092021-09-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fba-0890000000-310cbc77999e8d6b02f92021-09-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0295-2940000000-a936403339b6f3803c0c2021-09-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-ebc6f53e4803995495772021-09-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0090000000-73e320051b256d09bbb02021-09-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014r-0090000000-4c31cf3a8784d6c604f12021-09-25View Spectrum
MSMass Spectrum (Electron Ionization)splash10-03dj-2980000000-831c8190c59f98fc86232014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, experimental)Not Available2012-12-05View Spectrum
1D NMR13C NMR Spectrum (1D, 25.16 MHz, CDCl3, experimental)Not Available2014-09-23View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, CDCl3, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureRapid and complete absorption follows oral intake of ethinyl estradiol (bioavailability 43%).
Mechanism of ToxicityEstrogens 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. This cascade is initiated by initially binding to the estrogen receptors. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).
MetabolismHepatic. Quantitatively, the major metabolic pathway for ethinyl estradiol, both in rats and in humans, is aromatic hydroxylation, as it is for the natural estrogens. Half Life: 36 +/- 13 hours
Toxicity ValuesOral, mouse LD50: 1737 mg/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor treatment of moderate to severe vasomotor symptoms associated with the menopause, female hypogonadism, prostatic carcinoma-palliative therapy of advanced disease, breast cancer, as an oral contraceptive, and as emergency contraceptive.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females. The FDA label includes a black box warning that states that combination oral contraceptives with ethinyl estradiol should not be used in women over 35 years old who smoke due to the increased risk of serious cardiovascular side effects.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00977
HMDB IDHMDB01926
PubChem Compound ID5991
ChEMBL IDCHEMBL691
ChemSpider ID5770
KEGG IDC07534
UniProt IDNot Available
OMIM ID
ChEBI ID4903
BioCyc IDABIETADIENE
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkEthinylestradiol
References
Synthesis Reference

Andreas Sachse, “Method of female hormonal contraception using a fixed extended cycle hormonal preparation containing dienogest and ethinyl estradiol.” U.S. Patent US20060079491, issued April 13, 2006.

MSDSLink
General References
  1. Li X, Strauss L, Kaatrasalo A, Mayerhofer A, Huhtaniemi I, Santti R, Makela S, Poutanen M: Transgenic mice expressing p450 aromatase as a model for male infertility associated with chronic inflammation in the testis. Endocrinology. 2006 Mar;147(3):1271-7. Epub 2005 Nov 23. [16306085 ]
  2. Wernert N: [Immunohistochemistry of the prostate and prostate carcinomas]. Veroff Pathol. 1991;135:1-163. [2038892 ]
  3. Kaufer D, Ogle WO, Pincus ZS, Clark KL, Nicholas AC, Dinkel KM, Dumas TC, Ferguson D, Lee AL, Winters MA, Sapolsky RM: Restructuring the neuronal stress response with anti-glucocorticoid gene delivery. Nat Neurosci. 2004 Sep;7(9):947-53. Epub 2004 Aug 8. [15300253 ]
  4. Zhang L, Sukhareva M, Barker JL, Maric D, Hao Y, Chang YH, Ma W, O'Shaughnessy T, Rubinow DR: Direct binding of estradiol enhances Slack (sequence like a calcium-activated potassium channel) channels' activity. Neuroscience. 2005;131(2):275-82. [15708472 ]
  5. Herrero P, Soto PF, Dence CS, Kisrieva-Ware Z, Delano DA, Peterson LR, Gropler RJ: Impact of hormone replacement on myocardial fatty acid metabolism: potential role of estrogen. J Nucl Cardiol. 2005 Sep-Oct;12(5):574-81. [16171718 ]
  6. Shah MG, Maibach HI: Estrogen and skin. An overview. Am J Clin Dermatol. 2001;2(3):143-50. [11705091 ]
  7. Safi R, Kovacic A, Gaillard S, Murata Y, Simpson ER, McDonnell DP, Clyne CD: Coactivation of liver receptor homologue-1 by peroxisome proliferator-activated receptor gamma coactivator-1alpha on aromatase promoter II and its inhibition by activated retinoid X receptor suggest a novel target for breast-specific antiestrogen therapy. Cancer Res. 2005 Dec 15;65(24):11762-70. [16357189 ]
  8. vom Saal FS, Grant WM, McMullen CW, Laves KS: High fetal estrogen concentrations: correlation with increased adult sexual activity and decreased aggression in male mice. Science. 1983 Jun 17;220(4603):1306-9. [6857252 ]
  9. Schmitt PM, Gohil K, Kaufman MP: Spinal estrogen attenuates the exercise pressor reflex but has little effect on the expression of genes regulating neurotransmitters in the dorsal root ganglia. J Appl Physiol (1985). 2006 Mar;100(3):958-64. Epub 2005 Nov 23. [16306253 ]
  10. Kalaitzidis D, Ok J, Sulak L 2nd, Starczynowski DT, Gilmore TD: Characterization of a human REL-estrogen receptor fusion protein with a reverse conditional transforming activity in chicken spleen cells. Oncogene. 2004 Sep 30;23(45):7580-7. [15326488 ]
  11. Pierard-Franchimont C, Letawe C, Goffin V, Pierard GE: Skin water-holding capacity and transdermal estrogen therapy for menopause: a pilot study. Maturitas. 1995 Sep;22(2):151-4. [8538484 ]
  12. de la Monte SM, Moore GW, Hutchins GM: Metastatic behavior of prostate cancer. Cluster analysis of patterns with respect to estrogen treatment. Cancer. 1986 Aug 15;58(4):985-93. [3719562 ]
  13. Czernik PJ, Little JM, Barone GW, Raufman JP, Radominska-Pandya A: Glucuronidation of estrogens and retinoic acid and expression of UDP-glucuronosyltransferase 2B7 in human intestinal mucosa. Drug Metab Dispos. 2000 Oct;28(10):1210-6. [10997942 ]
  14. Harris H, Henderson R, Bhat R, Komm B: Regulation of metallothionein II messenger ribonucleic acid measures exogenous estrogen receptor-beta activity in SAOS-2 and LNCaPLN3 cells. Endocrinology. 2001 Feb;142(2):645-52. [11159835 ]
  15. Stabile LP, Davis AL, Gubish CT, Hopkins TM, Luketich JD, Christie N, Finkelstein S, Siegfried JM: Human non-small cell lung tumors and cells derived from normal lung express both estrogen receptor alpha and beta and show biological responses to estrogen. Cancer Res. 2002 Apr 1;62(7):2141-50. [11929836 ]
  16. Frolich A, Christensen L, Andersen J: Estrogen receptors appear undetectable in the C-cells of the human thyroid gland. Bone. 1990;11(6):393-6. [1706609 ]
  17. Siiteri PK: Review of studies on estrogen biosynthesis in the human. Cancer Res. 1982 Aug;42(8 Suppl):3269s-3273s. [7083184 ]
  18. Koehler KF, Helguero LA, Haldosen LA, Warner M, Gustafsson JA: Reflections on the discovery and significance of estrogen receptor beta. Endocr Rev. 2005 May;26(3):465-78. Epub 2005 Apr 27. [15857973 ]
  19. Moro L, Reineri S, Piranda D, Pietrapiana D, Lova P, Bertoni A, Graziani A, Defilippi P, Canobbio I, Torti M, Sinigaglia F: Nongenomic effects of 17beta-estradiol in human platelets: potentiation of thrombin-induced aggregation through estrogen receptor beta and Src kinase. Blood. 2005 Jan 1;105(1):115-21. Epub 2004 Jun 15. [15198955 ]
  20. Nakano Y, Oshima T, Ozono R, Ueda A, Oue Y, Matsuura H, Sanada M, Ohama K, Chayama K, Kambe M: Estrogen replacement suppresses function of thrombin stimulated platelets by inhibiting Ca(2+) influx and raising cyclic adenosine monophosphate. Cardiovasc Res. 2002 Feb 15;53(3):634-41. [11861034 ]
  21. FDA label.
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
AC505.41E-05 uMNVS_NR_hERNovascreen
AC500.044 uMOT_ER_ERaERa_0480Odyssey Thera
AC500.0502 uMOT_ER_ERaERa_1440Odyssey Thera
AC500.00211 uMOT_ERa_EREGFP_0120Odyssey Thera
AC500.003 uMOT_ERa_EREGFP_0480Odyssey Thera
AC500.000325 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
AC500.000589 uMTox21_ERa_LUC_BG1_AgonistTox21/NCGC
AC500.0061 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC500.0277 uMATG_ERa_TRANSAttagene
AC500.0107 uMATG_ERE_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
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
AC500.00515 uMNVS_NR_hARNovascreen
AC506.35 uMOT_AR_ARSRC1_0480Odyssey Thera
AC500.473 uMOT_AR_ARSRC1_0960Odyssey Thera
AC500.398 uMTox21_AR_BLA_Antagonist_ratioTox21/NCGC
AC503.89 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
AC500.0145 uMOT_ER_ERaERb_0480Odyssey Thera
AC500.0314 uMOT_ER_ERaERb_1440Odyssey Thera
AC500.0611 uMOT_ER_ERbERb_0480Odyssey Thera
AC500.0303 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. 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
AC500.023 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
5. Sodium-dependent serotonin transporter
General Function:
Serotonin:sodium symporter activity
Specific Function:
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular Weight:
70324.165 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.275 uMNVS_TR_hSERTNovascreen
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. 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
AC500.379 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
7. Sodium-dependent noradrenaline transporter
General Function:
Norepinephrine:sodium symporter activity
Specific Function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Molecular Weight:
69331.42 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.407 uMNVS_TR_hNETNovascreen
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. 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
AC501.33 uMNVS_NR_hGRNovascreen
AC500.697 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
9. Cytochrome P450 2C19
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.13 uMNVS_ADME_hCYP2C19Novascreen
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
10. Cytochrome P450 2J2
General Function:
Steroid hydroxylase activity
Specific Function:
This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible for the epoxidation of endogenous cardiac arachidonic acid pools.
Gene Name:
CYP2J2
Uniprot ID:
P51589
Molecular Weight:
57610.165 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.16 uMNVS_ADME_hCYP2J2Novascreen
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
11. 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
AC501.57 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 ]
Target Details
12. Cytochrome P450 3A5
General Function:
Oxygen binding
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:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.62 uMNVS_ADME_hCYP3A5Novascreen
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
13. 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
AC507.23 uMATG_PXR_TRANSAttagene
AC504.45 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
14. Cytochrome P450 2C9
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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.56 uMNVS_ADME_hCYP2C9Novascreen
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
15. Nuclear receptor subfamily 1 group I member 3
General Function:
Zinc ion binding
Specific Function:
Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element.
Gene Name:
NR1I3
Uniprot ID:
Q14994
Molecular Weight:
39942.145 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.49 uMNVS_NR_hCAR_AntagonistNovascreen
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
16. Bile acid receptor
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
Gene Name:
NR1H4
Uniprot ID:
Q96RI1
Molecular Weight:
55913.915 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.93 uMOT_SRC1_SRC1FXR_0480Odyssey 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
17. 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
AC508.01 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 ]