Norethindrone (T3D4745)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (6)XML
Targets (6)
Record Information
Version2.0
Creation Date2014-09-11 05:14:30 UTC
Update Date2014-12-24 20:26:56 UTC
Accession NumberT3D4745
Identification
Common NameNorethindrone
ClassSmall Molecule
DescriptionA synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception.
Compound Type
  • Contraceptive, Oral, Synthetic
  • Drug
  • Ester
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
(17-alpha)-17-Hydroxy-19-norpregn-4-en-20-yn-3-one
(17alpha)-17-Ethynyl-17-hydroxyestra-4,8(14),9-trien-3-one
17-alpha-Ethynyl-17-beta-hydroxy-4-estren-3-one
17-alpha-Ethynyl-17-hydroxy-4-estren-3-one
17-alpha-Ethynyl-19-norandrost-4-en-17-beta-ol-3-one
17-alpha-Ethynyl-19-nortestosterone
17-alpha-Ethynyl-4-estren-17-ol-3-one
17-beta-Hydroxy-19-norpregn-4-en-20-yn-3-one
17-Ethinyl-19-nor-testosterone
17-Ethynyl-17-hydroxyestr-4-en-3-one
17-Ethynyl-17beta-hydroxyestr-4-en-3-one
17-Ethynyl-19-Nortestosterone
17-Hydroxy-(17alpha)-19-Norpregn-4-en-20-yn-3-one
17-Hydroxy-17-alpha-19-Norpregn-4-en-20-yn-3-one
17-Hydroxy-19-nor-17-alpha-pregn-4-en-20-yn-3-one
17-Hydroxy-19-Nor-17alpha-pregn-4-en-20-yn-3-one
17alpha-Ethinyl-17alpha-Ethinyl-19-nortestosterone
17alpha-Ethinyl-19-Nortestosterone
17alpha-Ethinylestra-4-en-17beta-ol-3-one
17alpha-Ethynyl-17-hydroxy-4-estren-3-one
17alpha-ethynyl-17-hydroxy-Estr-4-en-3-one
17alpha-Ethynyl-17-hydroxyest-4-en-3-one
17alpha-Ethynyl-17beta-hydroxy-19-norandrost-4-en-3-one
17alpha-Ethynyl-17beta-hydroxyestr-4-en-3-one
17alpha-Ethynyl-19-nor-4-androsten-17beta-ol-3-one
17alpha-Ethynyl-19-norandrost-4-en-17beta-ol-3-one
17alpha-Ethynyl-19-nortestosterone
17alpha-Ethynyl-3-oxo-4-estren-17beta-ol
17alpha-Ethynyl-4-estren-17-ol-3-one
17alpha-pregn-4-en-20-yn-3-one
17beta-Hydroxy-17alpha-ethynylestr-4-en-3-one
17beta-Hydroxy-19-norpregn-4-en-20-yn-3-one
17α-ethinyl-19-nortestosterone
19-Nor-17-alpha-ethynyl-17-beta-hydroxy-4-androsten-3-one
19-Nor-17-alpha-ethynylandrosten-17-beta-ol-3-one
19-Nor-17-alpha-ethynyltestosterone
19-Nor-17-ethinyltestosterone
19-Nor-17alpha-Ethynyl-17beta-hydroxy-4-androsten-3-one
19-Nor-17alpha-Ethynylandrosten-17beta-ol-3-one
19-Nor-17alpha-ethynyltestosterone
19-nor-17α-ethynyltestosterone
19-Nor-ethindrone
19-Norethinyltestosterone
19-Norethisterone
4-Estren-17alpha-ethynyl-17beta-ol-3-one
Anhydrohydroxynorprogesterone
Anovule
Aygestin
Camila
Conludaf
Conludag
ENT
Errin
Ethinyl-19-nortestosterone
Ethinylnortestosterone
Ethynylnortestosterone
Gestest
HEATHER
Jencycla
Jolivette
LYZA
Menzol
Micronett
Micronor
Micronovum
Mini-Pe
Mini-pill
Minovlar
NET
Nor-Q.D.
Nor-QD
Noralutin
Norcolut
Noresthisterone
Norethisteron
Norethisterone
Norethisteronum
Norethyndron
Norethynodrone
Noretisterona
Norfor
Norgestin
Noriday
Norlutate
Norluten
Norlutin
Norluton
NORLYROC
Normapause
Norpregneninlone
Norpregneninolone
Primolut N
Primolut-N
Proluteasi
Utovlan
Utovlar
Chemical FormulaC20H26O2
Average Molecular Mass298.419 g/mol
Monoisotopic Mass298.193 g/mol
CAS Registry Number68-22-4
IUPAC Name(1S,2R,10R,11S,14R,15S)-14-ethynyl-14-hydroxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
Traditional Name(1S,2R,10R,11S,14R,15S)-14-ethynyl-14-hydroxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
SMILES[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H]
InChI IdentifierInChI=1S/C20H26O2/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/h1,12,15-18,22H,4-11H2,2H3/t15-,16+,17+,18-,19-,20-/m0/s1
InChI KeyInChIKey=VIKNJXKGJWUCNN-XGXHKTLJSA-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-oxo-delta-4-steroid
  • 3-oxosteroid
  • 17-hydroxysteroid
  • Oxosteroid
  • Hydroxysteroid
  • Delta-4-steroid
  • Cyclohexenone
  • Ynone
  • Cyclic alcohol
  • Tertiary alcohol
  • Cyclic ketone
  • Ketone
  • Acetylide
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Alcohol
  • Organooxygen compound
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic 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 Point203.5°C
Boiling PointNot Available
Solubility7.04 mg/L (at 25°C)
LogP2.97
Predicted Properties
PropertyValueSource
Water Solubility0.0067 g/LALOGPS
logP2.72ALOGPS
logP3.22ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)17.59ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity87.42 m³·mol⁻¹ChemAxon
Polarizability34.59 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, Positivesplash10-00w9-0690000000-7050c3192b843aecc4822017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-052f-1369000000-cfce41c0dca4a0c3cd9c2017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0002-0391000000-ae51cc90bb8f2161f1492017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0j59-2494000000-76c71f96c07e87ef89622017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-1910000000-f3f4bbf8cfe62ee9f76d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a5c-3900000000-4b2a5d95e4b6d50f16fc2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00ea-0790000000-60d1a1a37c0ba98d6a4a2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00e9-0890000000-5d3b8210450a1c43b1192017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0002-0391000000-ae51cc90bb8f2161f1492017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0ar0-3920000000-e31fa7c9e871f2e398462017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-001j-0930000000-9c2fc72a1b360913fb562021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-005c-0910000000-ef775abfdf43d67a42252021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 80V, Positivesplash10-0a5c-3900000000-11a6390c5bc5438291352021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0002-0391000000-7b2e411df9eccc111c8e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0002-0091000000-3a83c5fc59fdaea612312021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 55V, Positivesplash10-0a4i-1910000000-f3f4bbf8cfe62ee9f76d2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-00ea-0790000000-1844e6f664d23868bbab2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-004l-0900000000-623cab7c657eda4d2f5f2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-0002-0090000000-412f7f0b9259fe7593722021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 55V, Positivesplash10-00e9-0890000000-d8c560fa1ac40e4ba22f2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-0a59-2910000000-7b16e32a71f6c1df6d1e2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0090000000-ec79e2d15a020c198dde2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001m-0290000000-b8f5efd6d7713f50f65c2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0l5l-2980000000-14cb82df2a3c251f955e2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-eab48ea9142da299d9232016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0090000000-64471e6cc8b0f3e495b52016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00l6-0090000000-ccad820f0e5b5559e8e82016-08-03View Spectrum
MSMass Spectrum (Electron Ionization)splash10-01rt-4950000000-fcbe8bf03b1aa103152b2014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, CDCl3, experimental)Not Available2014-09-20View Spectrum
Toxicity Profile
Route of ExposureNorethindrone acetate is completely and rapidly deacetylated to norethindrone (NET) after oral administration, and the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone. Norethindrone is rapidly absorbed from norethindrone acetate, in which maximum plasma concentration occur 2 hours post-dose (Tmax). When a single dose is given to healthy women, the Cmax is 26.19 Њ± 6.19 hours. The AUC (0-inf) is 166.90 Њ± 56.28 ng/mL*h. Absolute oral bioavailability is approximately 64%. The effect of food on the pharmacokinetics of norethindrone acetate is unknown.
Mechanism of ToxicityProgestins diffuse freely into target cells and bind to the progesterone receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH surge.
MetabolismHepatic. Norethindrone is extensively metabolized, primarily via reduction. It also undergoes sulfate and glucuronide conjugation. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites. Route of Elimination: Norethindrone is excreted in both urine and feces, primarily as metabolites. Half Life: 8.51±2.19 (when a single dose is given to healthy women)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (18)
Uses/SourcesNorethindrone acetate is indicated for the treatment of secondary amenorrhea, endometriosis, and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00717
HMDB IDHMDB14855
PubChem Compound ID6230
ChEMBL IDCHEMBL1162
ChemSpider ID5994
KEGG IDC05028
UniProt IDNot Available
OMIM ID
ChEBI ID7627
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNDR
ACToR IDNot Available
Wikipedia LinkNorethindrone
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Knox SA, Viney RC, Gu Y, Hole AR, Fiebig DG, Street DJ, Haas MR, Weisberg E, Bateson D: The effect of adverse information and positive promotion on women's preferences for prescribed contraceptive products. Soc Sci Med. 2013 Apr;83:70-80. doi: 10.1016/j.socscimed.2012.12.025. Epub 2013 Jan 5. [23351426 ]
  2. Karkar A: Pregnancy and contraceptive issues in renal transplant recipients. Saudi J Kidney Dis Transpl. 2008 Mar;19(2):165-73. [18310862 ]
  3. Debski R, Kotarski J, Paszkowski T, Pawelczyk L, Skrzypulec V, Tomaszewski J: [The statement of Polish Gynecological Society experts on oral use of contraceptive 75 microg desogestrel minipill in different clinical cases--state of art in 2008]. Ginekol Pol. 2009 Jan;80(1):63-75. [19323063 ]
  4. Rabe T, Grunwald K, Runnebaum B: [Future prospects in contraception]. Arch Gynecol Obstet. 1995;257(1-4):541-7. [8579440 ]
  5. Tscherne G: [Benefits and risks of hormonal contraception]. Gynakol Geburtshilfliche Rundsch. 1992;32(3):174-6. [1467664 ]
  6. Spornitz UM: The functional morphology of the human endometrium and decidua. Adv Anat Embryol Cell Biol. 1992;124:1-99. [1561944 ]
  7. Kovacs G: Progestogen-only pills and bleeding disturbances. Hum Reprod. 1996 Oct;11 Suppl 2:20-3. [8982741 ]
  8. Lauritzen C: [Prevention of conception in adolescence]. Ther Umsch. 1994 May;51(5):314-24. [8016756 ]
  9. Emergency contraception hot line launched. Reprod Freedom News. 1996 Feb 23;5(4):7. [12290778 ]
  10. Maximizing the use of the progestin minipill. Contracept Technol Update. 1999 Feb;20(2):19-21. [12294591 ]
  11. Dorea JG, Miazaki ES: The effects of oral contraceptive use on iron and copper concentrations in breast milk. Fertil Steril. 1999 Aug;72(2):297-301. [10438999 ]
  12. Benagiano G, Bastianelli C, Farris M: Hormonal contraception: state of the art and future perspectives. Minerva Ginecol. 2007 Jun;59(3):241-70. [17576403 ]
  13. Benagiano G, Primiero FM: Seventy-five microgram desogestrel minipill, a new perspective in estrogen-free contraception. Ann N Y Acad Sci. 2003 Nov;997:163-73. [14644823 ]
  14. Is Cerazette the minipill of choice? Drug Ther Bull. 2003 Sep;41(9):68-9. [14531209 ]
  15. Benagiano G, Bastianelli C, Farris M: Contraception today. Ann N Y Acad Sci. 2006 Dec;1092:1-32. [17308130 ]
  16. Helleday J, Siwers B, Ritzen EM, Carlstrom K: Subnormal androgen and elevated progesterone levels in women treated for congenital virilizing 21-hydroxylase deficiency. J Clin Endocrinol Metab. 1993 Apr;76(4):933-6. [8473408 ]
  17. FDA label
  18. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. 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
AC500.438 uMATG_AR_TRANSAttagene
AC500.000505 uMNVS_NR_hARNovascreen
AC500.00777 uMOT_AR_ARSRC1_0480Odyssey Thera
AC500.0065 uMOT_AR_ARSRC1_0960Odyssey Thera
AC500.00219 uMTox21_AR_BLA_Agonist_ratioTox21/NCGC
AC500.101 uMTox21_AR_BLA_Antagonist_ratioTox21/NCGC
AC500.00707 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
2. 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
AC500.00386 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC500.0661 uMATG_ERa_TRANSAttagene
AC500.0673 uMATG_ERE_CISAttagene
AC500.199 uMNVS_NR_hERNovascreen
AC500.54 uMOT_ERa_EREGFP_0120Odyssey Thera
AC501.28 uMOT_ERa_EREGFP_0480Odyssey Thera
AC500.449 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
AC500.018 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
3. 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
AC500.00763 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
4. 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
AC500.191 uMNVS_NR_hGRNovascreen
AC500.6 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
5. 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
AC502.89 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
6. 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
AC508.87 uMOT_ER_ERaERb_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 ]