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Bisphenol A (T3D0637)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (43)XML
Targets (43)
Record Information
Version2.0
Creation Date2009-03-19 21:46:58 UTC
Update Date2014-12-24 20:22:27 UTC
Accession NumberT3D0637
Identification
Common NameBisphenol A
ClassSmall Molecule
DescriptionBisphenol A, commonly abbreviated as BPA, is an organic compound with two phenol functional groups. It is a difunctional building block of several important plastics and plastic additives. With an annual production of 2-3 million metric tonnes, it is an important monomer in the production of polycarbonate. It is a potential food contaminant arising from its use in reusable polycarbonate food containers such as water carboys, baby bottles and kitchen utensils. Suspected of being hazardous to humans since the 1930s, concerns about the use of bisphenol A in consumer products were regularly reported in the news media in 2008 after several governments issued reports questioning its safety, and some retailers removed baby bottles and other children's products made from it from their shelves.
Compound Type
  • Aromatic Hydrocarbon
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Metabolite
  • Organic Compound
  • Pesticide
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(1-methylethylidene)bis-Phenol
1,1'-(1-Methylethylidene)bisphenylol, 9CI
2, 2-Bis(4-hydroxyphenyl)propane
2, 2-Bis(hydroxyphenyl)propane
2, 2-Di(4-phenylol)propane
2,2'-Bis(4-hydroxyphenyl)propane
2,2-(4,4'-Dihydroxydiphenyl)propane
2,2-(4,4-Dihydroxydiphenyl)propane
2,2-Bis (4-hydroxyphenol) propane
2,2-Bis(4'-hydroxyphenyl)propane
2,2-Bis(4,4'-hydroxyphenyl)propane
2,2-Bis(4-hydroxyphenyl)propane
2,2-Bis(hydroxyphenyl)propane
2,2-Bis(p-hydroxyphenyl)-Propane
2,2-Bis(p-hydroxyphenyl)propane
2,2-Bis-4'-hydroxyfenylpropan
2,2-Bis[4-Hydroxyphenyl]propane
2,2-Di(4-hydroxyphenyl)propane
2,2-Di(4-phenylol)propane
2,2-Di-(4'-Hydroxyphenyl)-propane
4, 4'-Bisphenol A
4, 4'-Dihydroxydiphenyl-2,2-propane
4, 4'-Dihydroxydiphenyldimethylmethane
4, 4'-Dihydroxydiphenylpropane
4,4' Isopropylidinediphenol
4,4'-(1-Methylethane-1,1-diyl)diphenol
4,4'-(1-Methylethylidene)bis-Phenol
4,4'-(1-Methylethylidene)bisphenol
4,4'-(1-Methylethylidene)bisphenol, 9CI
4,4'-(Propane-2,2-diyl)diphenol
4,4'-Bisphenol A
4,4'-Dihydroxdiphenylpropane
4,4'-Dihydroxy-2,2-diphenylpropane
4,4'-Dihydroxydiphenyl-2,2-propane
4,4'-Dihydroxydiphenyldimethylmethane
4,4'-Dihydroxydiphenylpropane
4,4'-Dimethylmethylenedi-Phenol
4,4'-Dimethylmethylenediphenol
4,4'-Isopropylidene diphenol
4,4'-Isopropylidenebisphenol
4,4'-Isopropylidenebis[phenol]
4,4'-Isopropylidenedi-Phenol
4,4'-Isopropylidenediphenol
4,4'-Isopropylidenediphenol B
4,4'-Propane-2,2-diyldiphenol
4,4-Isopropylidenediphenol
4,4[-Isopropylidenediphenol
4-[1-(4-Hydroxyphenyl)-1-methylethyl]phenol
beta, beta'-Bis(p-hydroxyphenyl)propane
beta,beta'-Bis(p-hydroxyphenyl)propane
beta,beta-Di-(p-hydroxyphenyl)propane
beta-Di-(p-hydroxyphenyl)propane
beta-Di-p-hydroxyphenylpropane
Biphenol a
Bis(4-hyd roxyphenyl) dimethylmethane
Bis(4-hydroxyphenyl) dimethylmethane
Bis(4-hydroxyphenyl) propane
Bis(4-hydroxyphenyl)dimethylmethane
Bis(4-hydroxyphenyl)propane
Bis(p-hydroxyphenyl)propane
Bisferol a
Bisphenol
Bisphenol a
Bisphenol a (bpa)
Bisphenol a, disodium salt
Bisphenol a, sodium salt
Bisphenol a.
BPA
Di-2,2-(4-Hydroxyphenyl)propane
Dian
Diano
Dimethyl bis(p-hydroxyphenyl)methane
Dimethylbis(p-hydroxyphenyl)methane
Dimethylmethylene-p,p'-diphenol
Diphenylolpropane
Hydrogenated bisphenol a
Ipognox 88
Isopropylidenebis(4-hydroxybenzene)
Millad hbpa
Noname
p, p'-Dihydroxydiphenyldimethylmethane
p, p'-Dihydroxydiphenylpropane
p, p'-Isopropylidenediphenol
p,p'-Bisphenol a
p,p'-Dihydroxydiphenyldimethylmethane
p,p'-Dihydroxydiphenylpropane
p,p'-Isopropylidenebisphenol
p,p'-Isopropylidenediphenol
Parabis
Parabis a
Rikabanol
Ucar bisphenol a
Ucar bisphenol HP
Chemical FormulaC15H16O2
Average Molecular Mass228.286 g/mol
Monoisotopic Mass228.115 g/mol
CAS Registry Number1980-05-07
IUPAC Name4-[2-(4-hydroxyphenyl)propan-2-yl]phenol
Traditional Namebisphenol-A
SMILESCC(C)(C1=CC=C(O)C=C1)C1=CC=C(O)C=C1
InChI IdentifierInChI=1S/C15H16O2/c1-15(2,11-3-7-13(16)8-4-11)12-5-9-14(17)10-6-12/h3-10,16-17H,1-2H3
InChI KeyInChIKey=IISBACLAFKSPIT-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as bisphenols. These are methylenediphenols, HOC6H4CH2C6H4OH, commonly p,p-methylenediphenol, and their substitution products (generally derived from condensation of two equivalent amounts of a phenol with an aldehyde or ketone).
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentBisphenols
Alternative Parents
Substituents
  • Bisphenol
  • Phenylpropane
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceCrystallizes as prisms from dil acetic acid and as needles from water (3).
Experimental Properties
PropertyValue
Melting Point156 - 157°C
Boiling PointNot Available
Solubility0.12 mg/mL at 25°C
LogP3.32
Predicted Properties
PropertyValueSource
Water Solubility0.086 g/LALOGPS
logP3.81ALOGPS
logP4.04ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)9.78ChemAxon
pKa (Strongest Basic)-5.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity79.28 m³·mol⁻¹ChemAxon
Polarizability25.41 ųChemAxon
Number of Rings2ChemAxon
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-2290000000-5a53b16778a578ff5d0d2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-03di-2290000000-5a53b16778a578ff5d0d2018-05-18View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-03g0-1790000000-7521406d051aed77fe2f2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0ab9-6289000000-59b1fac0d668364456292017-10-06View 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 - LC-ESI-ITFT , positivesplash10-0zfs-4960000000-b4ebb7f1ff08fbb41adb2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-1090000000-80a2709d727e93053cd12017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0090000000-c33246c7d9d8b300c90c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0090000000-e5f7d4cb43ef56a850562017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0532-9340000000-c3298310f84ad87b13102017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-000t-9000000000-75784b9156574d6f17622017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4j-1900000000-1316f0a328865698ba142017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-000t-9000000000-75784b9156574d6f17622021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0zfs-4960000000-b4ebb7f1ff08fbb41adb2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-004i-0090000000-c33246c7d9d8b300c90c2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-004i-1090000000-80a2709d727e93053cd12021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-004i-0090000000-e5f7d4cb43ef56a850562021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-0532-9340000000-c3298310f84ad87b13102021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0a4j-1900000000-1316f0a328865698ba142021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0090000000-8791a2cf0310bf33a81e2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-0190000000-ee807d7dec5640d38d182016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01rb-2920000000-e15c6a1d966dd429fe3f2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0090000000-0494eb6f9068e16e1d992016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-0090000000-e9b5452c25e607f299502016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-002f-9470000000-9d3d569c0a3f755f123f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-002r-1960000000-42e45d340eea8ee9e3db2021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-3900000000-8ef860db11d71a8b2f2e2021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-2900000000-61ebc2c60a263652b43e2021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-3090000000-27243d7aedeaef4a196c2021-09-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0095-3940000000-3863b01420a8ec7c47d32021-09-25View Spectrum
MSMass Spectrum (Electron Ionization)splash10-03di-3590000000-0cd99fd08fc2fad698f32014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, DMSO-d6, experimental)Not Available2014-09-20View Spectrum
Toxicity Profile
Route of ExposureOral (11) ; inhalation (11) ; dermal (11)
Mechanism of ToxicityBisphenol is an endocrine disruptor. Low doses of bisphenol A can mimic the body's own hormones, possibly causing negative health effects. There is thus concern that long term low dose exposure to bisphenol A may induce chronic toxicity in humans (10).
MetabolismBisphenol A (BPA) is rapidly absorbed from the gastrointestinal tract after ingestionand is then converted to a number of metabolites, mainly BPA glucuronide, in the liver . Metabloites of Bsiphenol A (BPA) include isopropyl-hydroxyphenol (produced by the cleavage of BPA), a bisphenol A glutathione conjugate, glutathionyl-phenol, glutathionyl 4-isopropylphenol, and BPA dimers. The monoglucuronide conjugate was the major urinary metabolite; unchanged BPA is the principal component excreted in feces (1, 2).
Toxicity ValuesLD50: 2230 mg/kg (Oral, Rabbit) (8)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesBisphenol A is used primarily to make plastics, and products containing bisphenol A-based plastics have been in commerce for more than 50 years. It is used in the synthesis of polyesters, polysulfones, and polyether ketones, as an antioxidant in some plasticizers, and as a polymerization inhibitor in PVC. It is a key monomer in production of polycarbonate plastic and epoxy resins. Polycarbonate plastic, which is clear and nearly shatter-proof, is used to make a variety of common products including baby and water bottles, sports equipment, medical and dental devices, dental fillings and sealants, eyeglass lenses, CDs and DVDs, and household electronics.[6] Epoxy resins containing bisphenol A are used as coatings on the inside of almost all food and beverage cans. Bisphenol A is also a precursor to the flame retardant, tetrabromobisphenol A, and was formerly used as a fungicide. (11)
Minimum Risk LevelNot Available
Health EffectsPermanent changes to genital tract, changes in breast tissue that predispose cells to hormones and carcinogens, increased prostate weight 30%, lower bodyweight, increase of anogenital distance in both genders, signs of early puberty and longer estrus, decline in testicular testosterone, breast cells predisposed to cancer, prostate cells more sensitive to hormones and cancer, decreased maternal behaviors, reversed the normal sex differences in brain structure and behavior, U.S. human exposure limit (not a result from an animal study, but a guideline set by EPA). (11)
SymptomsBisphenol A has low acute toxicity, with an oral LD50 of 3250 mg/kg in rats, but it is an endocrine disruptor. Low doses of bisphenol A can mimic the body's own hormones, possibly causing negative health effects. There is thus concern that long term low dose exposure to bisphenol A may induce chronic toxicity in humans. (11)
TreatmentConsider dilution immediately after ingestion. Insertion of a specialized nasogastric tube after confirmation of a circumferential burn may prevent strictures. In case of inhalation, move patient to fresh air and monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. In case of eye contact, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. Decontaminate skin or mucous membranes immediately with water and a soft sponge. (6)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB06973
HMDB IDHMDB32133
PubChem Compound ID6623
ChEMBL IDNot Available
ChemSpider ID6371
KEGG IDC13624
UniProt IDNot Available
OMIM ID
ChEBI ID33216
BioCyc IDCPD-10489
CTD IDC006780
Stitch IDBisphenol A
PDB ID2OH
ACToR ID183
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D0637.pdf
General References
  1. Pottenger LH, Domoradzki JY, Markham DA, Hansen SC, Cagen SZ, Waechter JM Jr: The relative bioavailability and metabolism of bisphenol A in rats is dependent upon the route of administration. Toxicol Sci. 2000 Mar;54(1):3-18. [10746927 ]
  2. Jaeg JP, Perdu E, Dolo L, Debrauwer L, Cravedi JP, Zalko D: Characterization of new bisphenol a metabolites produced by CD1 mice liver microsomes and S9 fractions. J Agric Food Chem. 2004 Jul 28;52(15):4935-42. [15264938 ]
  3. Sylvester PW, McIntyre BS, Gapor A, Briski KP: Vitamin E inhibition of normal mammary epithelial cell growth is associated with a reduction in protein kinase C(alpha) activation. Cell Prolif. 2001 Dec;34(6):347-57. [11736999 ]
  4. Kim JY, Jeong HG: Down-regulation of inducible nitric oxide synthase and tumor necrosis factor-alpha expression by bisphenol A via nuclear factor-kappaB inactivation in macrophages. Cancer Lett. 2003 Jun 30;196(1):69-76. [12860292 ]
  5. Masuda S, Terashima Y, Sano A, Kuruto R, Sugiyama Y, Shimoi K, Tanji K, Yoshioka H, Terao Y, Kinae N: Changes in the mutagenic and estrogenic activities of bisphenol A upon treatment with nitrite. Mutat Res. 2005 Aug 1;585(1-2):137-46. [15936980 ]
  6. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  7. Lide DR, Milne GWA (eds) (1994). Handbook of Data on Organic Compounds. Volume I. 3rd ed. Boca Raton, FL: CRC Press, Inc.
  8. Verschueren K (2001). Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. New York, NY: John Wiley & Sons.
  9. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
  10. Wikipedia. Tetrabromobisphenol A. Last Updated 30 April 2009. [Link]
  11. Wikipedia. Bisphenol A. Last Updated 25 June 2009. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. 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
AC500.24 uMNVS_NR_hCAR_AntagonistNovascreen
AC500.08 uMNVS_NR_hCAR_AntagonistNovascreen
References
  1. Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [20869355 ]
  2. DeKeyser JG, Laurenzana EM, Peterson EC, Chen T, Omiecinski CJ: Selective phthalate activation of naturally occurring human constitutive androstane receptor splice variants and the pregnane X receptor. Toxicol Sci. 2011 Apr;120(2):381-91. doi: 10.1093/toxsci/kfq394. Epub 2011 Jan 12. [21227907 ]
  3. 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
AC501.10 uMATG_ERa_TRANSAttagene
AC500.64 uMATG_ERE_CISAttagene
AC501.72 uMNCGC_ERalpha_AgonistNCGC
AC500.71 uMNVS_NR_hERNovascreen
AC500.45 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC502.80 uMATG_ERa_TRANSAttagene
AC500.68 uMATG_ERE_CISAttagene
AC500.13 uMNVS_NR_hERNovascreen
AC505.61 uMOT_ER_ERaERa_0480Odyssey Thera
AC504.64 uMOT_ER_ERaERa_1440Odyssey Thera
AC500.84 uMOT_ERa_EREGFP_0120Odyssey Thera
AC501.05 uMOT_ERa_EREGFP_0480Odyssey Thera
AC501.16 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
AC500.36 uMTox21_ERa_LUC_BG1_AgonistTox21/NCGC
References
  1. Furuya M, Adachi K, Kuwahara S, Ogawa K, Tsukamoto Y: Inhibition of male chick phenotypes and spermatogenesis by Bisphenol-A. Life Sci. 2006 Mar 6;78(15):1767-76. Epub 2005 Nov 16. [16297413 ]
  2. Wober J, Weisswange I, Vollmer G: Stimulation of alkaline phosphatase activity in Ishikawa cells induced by various phytoestrogens and synthetic estrogens. J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):227-33. [12650720 ]
  3. 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. 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
AC504.92 uMATG_PXR_TRANSAttagene
AC500.20 uMNVS_NR_hPXRNovascreen
References
  1. Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [16054614 ]
  2. Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [20869355 ]
  3. Kuzbari O, Peterson CM, Franklin MR, Hathaway LB, Johnstone EB, Hammoud AO, Lamb JG: Comparative analysis of human CYP3A4 and rat CYP3A1 induction and relevant gene expression by bisphenol A and diethylstilbestrol: implications for toxicity testing paradigms. Reprod Toxicol. 2013 Jun;37:24-30. doi: 10.1016/j.reprotox.2013.01.005. Epub 2013 Feb 4. [23384967 ]
  4. Molina-Molina JM, Amaya E, Grimaldi M, Saenz JM, Real M, Fernandez MF, Balaguer P, Olea N: In vitro study on the agonistic and antagonistic activities of bisphenol-S and other bisphenol-A congeners and derivatives via nuclear receptors. Toxicol Appl Pharmacol. 2013 Oct 1;272(1):127-36. doi: 10.1016/j.taap.2013.05.015. Epub 2013 May 25. [23714657 ]
  5. Sui Y, Park SH, Helsley RN, Sunkara M, Gonzalez FJ, Morris AJ, Zhou C: Bisphenol A increases atherosclerosis in pregnane X receptor-humanized ApoE deficient mice. J Am Heart Assoc. 2014 Apr 22;3(2):e000492. doi: 10.1161/JAHA.113.000492. [24755147 ]
  6. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
4. Estrogen receptor beta
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
Gene Name:
ESR2
Uniprot ID:
Q92731
Molecular Weight:
59215.765 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.21 uMOT_ER_ERaERb_0480Odyssey Thera
AC502.44 uMOT_ER_ERaERb_1440Odyssey Thera
AC500.60 uMOT_ER_ERbERb_0480Odyssey Thera
AC500.52 uMOT_ER_ERbERb_1440Odyssey Thera
References
  1. Furuya M, Adachi K, Kuwahara S, Ogawa K, Tsukamoto Y: Inhibition of male chick phenotypes and spermatogenesis by Bisphenol-A. Life Sci. 2006 Mar 6;78(15):1767-76. Epub 2005 Nov 16. [16297413 ]
  2. Matsushima A, Liu X, Okada H, Shimohigashi M, Shimohigashi Y: Bisphenol AF is a full agonist for the estrogen receptor ERalpha but a highly specific antagonist for ERbeta. Environ Health Perspect. 2010 Sep;118(9):1267-72. doi: 10.1289/ehp.0901819. Epub 2010 Apr 28. [20427257 ]
  3. 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
AC505.63 uMNVS_NR_hPRNovascreen
References
  1. Scippo ML, Argiris C, Van De Weerdt C, Muller M, Willemsen P, Martial J, Maghuin-Rogister G: Recombinant human estrogen, androgen and progesterone receptors for detection of potential endocrine disruptors. Anal Bioanal Chem. 2004 Feb;378(3):664-9. Epub 2003 Oct 25. [14579009 ]
  2. 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. 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
IC505.9 uMNot AvailableBindingDB 29608
AC505.79 uMNVS_NR_hARNovascreen
References
  1. Wetherill YB, Hess-Wilson JK, Comstock CE, Shah SA, Buncher CR, Sallans L, Limbach PA, Schwemberger S, Babcock GF, Knudsen KE: Bisphenol A facilitates bypass of androgen ablation therapy in prostate cancer. Mol Cancer Ther. 2006 Dec;5(12):3181-90. [17172422 ]
  2. Maruyama K, Nakamura M, Tomoshige S, Sugita K, Makishima M, Hashimoto Y, Ishikawa M: Structure-activity relationships of bisphenol A analogs at estrogen receptors (ERs): discovery of an ERalpha-selective antagonist. Bioorg Med Chem Lett. 2013 Jul 15;23(14):4031-6. doi: 10.1016/j.bmcl.2013.05.067. Epub 2013 May 30. [23768907 ]
  3. Teng C, Goodwin B, Shockley K, Xia M, Huang R, Norris J, Merrick BA, Jetten AM, Austin CP, Tice RR: Bisphenol A affects androgen receptor function via multiple mechanisms. Chem Biol Interact. 2013 May 25;203(3):556-64. doi: 10.1016/j.cbi.2013.03.013. Epub 2013 Apr 4. [23562765 ]
  4. 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. Estrogen-related receptor gamma
General Function:
Zinc ion binding
Specific Function:
Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Induces the expression of PERM1 in the skeletal muscle.
Gene Name:
ESRRG
Uniprot ID:
P62508
Molecular Weight:
51305.485 Da
References
  1. Matsushima A, Kakuta Y, Teramoto T, Koshiba T, Liu X, Okada H, Tokunaga T, Kawabata S, Kimura M, Shimohigashi Y: Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma. J Biochem. 2007 Oct;142(4):517-24. Epub 2007 Aug 30. [17761695 ]
  2. Okada H, Tokunaga T, Liu X, Takayanagi S, Matsushima A, Shimohigashi Y: Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptor-gamma. Environ Health Perspect. 2008 Jan;116(1):32-8. doi: 10.1289/ehp.10587. [18197296 ]
  3. Babu S, Vellore NA, Kasibotla AV, Dwayne HJ, Stubblefield MA, Uppu RM: Molecular docking of bisphenol A and its nitrated and chlorinated metabolites onto human estrogen-related receptor-gamma. Biochem Biophys Res Commun. 2012 Sep 21;426(2):215-20. doi: 10.1016/j.bbrc.2012.08.065. Epub 2012 Aug 23. [22935422 ]
Target Details
8. Aryl hydrocarbon receptor
General Function:
Transcription regulatory region dna binding
Specific Function:
Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
Gene Name:
AHR
Uniprot ID:
P35869
Molecular Weight:
96146.705 Da
References
  1. Wang H, Li J, Gao Y, Xu Y, Pan Y, Tsuji I, Sun ZJ, Li XM: Xeno-oestrogens and phyto-oestrogens are alternative ligands for the androgen receptor. Asian J Androl. 2010 Jul;12(4):535-47. doi: 10.1038/aja.2010.14. Epub 2010 May 3. [20436506 ]
Target Details
9. G-protein coupled estrogen receptor 1
General Function:
Steroid hormone binding
Specific Function:
G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP production, calcium mobilization and tyrosine kinase Src inducing the release of heparin-bound epidermal growth factor (HB-EGF) and subsequent transactivation of the epidermal growth factor receptor (EGFR), activating downstream signaling pathways such as PI3K/Akt and ERK/MAPK. Mediates pleiotropic functions among others in the cardiovascular, endocrine, reproductive, immune and central nervous systems. Has a role in cardioprotection by reducing cardiac hypertrophy and perivascular fibrosis in a RAMP3-dependent manner. Regulates arterial blood pressure by stimulating vasodilation and reducing vascular smooth muscle and microvascular endothelial cell proliferation. Plays a role in blood glucose homeostasis contributing to the insulin secretion response by pancreatic beta cells. Triggers mitochondrial apoptosis during pachytene spermatocyte differentiation. Stimulates uterine epithelial cell proliferation. Enhances uterine contractility in response to oxytocin. Contributes to thymic atrophy by inducing apoptosis. Attenuates TNF-mediated endothelial expression of leukocyte adhesion molecules. Promotes neuritogenesis in developing hippocampal neurons. Plays a role in acute neuroprotection against NMDA-induced excitotoxic neuronal death. Increases firing activity and intracellular calcium oscillations in luteinizing hormone-releasing hormone (LHRH) neurons. Inhibits early osteoblast proliferation at growth plate during skeletal development. Inhibits mature adipocyte differentiation and lipid accumulation. Involved in the recruitment of beta-arrestin 2 ARRB2 at the plasma membrane in epithelial cells. Functions also as a receptor for aldosterone mediating rapid regulation of vascular contractibility through the PI3K/ERK signaling pathway. Involved in cancer progression regulation. Stimulates cancer-associated fibroblast (CAF) proliferation by a rapid genomic response through the EGFR/ERK transduction pathway. Associated with EGFR, may act as a transcription factor activating growth regulatory genes (c-fos, cyclin D1). Promotes integrin alpha-5/beta-1 and fibronectin (FN) matrix assembly in breast cancer cells.
Gene Name:
GPER1
Uniprot ID:
Q99527
Molecular Weight:
42247.12 Da
References
  1. Thomas P, Dong J: Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: a potential novel mechanism of endocrine disruption. J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):175-9. Epub 2006 Nov 7. [17088055 ]
Target Details
10. Nuclear receptor ROR-gamma
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates the circadian expression of clock genes such as CRY1, ARNTL/BMAL1 and NR1D1 in peripheral tissues and in a tissue-selective manner. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORC-mediated activation of the expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A. Negative regulator of adipocyte differentiation through the regulation of early phase genes expression, such as MMP3. Controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. In liver, has specific and redundant functions with RORA as positive or negative modulator of expression of genes encoding phase I and Phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as SULT1E1. Also plays also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC and PCK1. Regulates the rhythmic expression of PROX1 and promotes its nuclear localization (By similarity). Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity (PubMed:26160376).Isoform 2: Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyer's patches. Required for the generation of LTi (lymphoid tissue inducer) cells. Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2. Also plays a key role, downstream of IL6 and TGFB and synergistically with RORA, for lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. May also play a role in the pre-TCR activation cascade leading to the maturation of alpha/beta T-cells and may participate in the regulation of DNA accessibility in the TCR-J(alpha) locus.
Gene Name:
RORC
Uniprot ID:
P51449
Molecular Weight:
58194.845 Da
References
  1. Nishigori M, Nose T, Shimohigashi Y: Highly potent binding and inverse agonist activity of bisphenol A derivatives for retinoid-related orphan nuclear receptor RORgamma. Toxicol Lett. 2012 Jul 20;212(2):205-11. doi: 10.1016/j.toxlet.2012.05.020. Epub 2012 May 29. [22659100 ]
Target Details
11. Peroxisome proliferator-activated receptor alpha
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.
Gene Name:
PPARA
Uniprot ID:
Q07869
Molecular Weight:
52224.595 Da
References
  1. Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]
Target Details
12. Peroxisome proliferator-activated receptor delta
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.
Gene Name:
PPARD
Uniprot ID:
Q03181
Molecular Weight:
49902.99 Da
References
  1. Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]
Target Details
13. Peroxisome proliferator-activated receptor gamma
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
References
  1. Riu A, le Maire A, Grimaldi M, Audebert M, Hillenweck A, Bourguet W, Balaguer P, Zalko D: Characterization of novel ligands of ERalpha, Erbeta, and PPARgamma: the case of halogenated bisphenol A and their conjugated metabolites. Toxicol Sci. 2011 Aug;122(2):372-82. doi: 10.1093/toxsci/kfr132. Epub 2011 May 27. [21622942 ]
Target Details
14. Prostaglandin G/H synthase 1
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells.
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
References
  1. Ito Y, Ito T, Karasawa S, Enomoto T, Nashimoto A, Hase Y, Sakamoto S, Mimori T, Matsumoto Y, Yamaguchi Y, Handa H: Identification of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel target of bisphenol A. PLoS One. 2012;7(12):e50481. doi: 10.1371/journal.pone.0050481. Epub 2012 Dec 5. [23227178 ]
Target Details
15. Protein disulfide-isomerase
General Function:
Protein heterodimerization activity
Specific Function:
This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307).
Gene Name:
P4HB
Uniprot ID:
P07237
Molecular Weight:
57115.795 Da
References
  1. Hiroi T, Okada K, Imaoka S, Osada M, Funae Y: Bisphenol A binds to protein disulfide isomerase and inhibits its enzymatic and hormone-binding activities. Endocrinology. 2006 Jun;147(6):2773-80. Epub 2006 Mar 16. [16543366 ]
Target Details
16. Retinoic acid receptor RXR-alpha
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.
Gene Name:
RXRA
Uniprot ID:
P19793
Molecular Weight:
50810.835 Da
References
  1. Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]
Target Details
17. Retinoic acid receptor RXR-beta
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Specifically binds 9-cis retinoic acid (9C-RA).
Gene Name:
RXRB
Uniprot ID:
P28702
Molecular Weight:
56921.38 Da
References
  1. Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]
Target Details
18. Retinoic acid receptor RXR-gamma
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity).
Gene Name:
RXRG
Uniprot ID:
P48443
Molecular Weight:
50870.72 Da
References
  1. Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]
Target Details
19. Sodium channel protein type 5 subunit alpha
General Function:
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 Da
References
  1. O'Reilly AO, Eberhardt E, Weidner C, Alzheimer C, Wallace BA, Lampert A: Bisphenol A binds to the local anesthetic receptor site to block the human cardiac sodium channel. PLoS One. 2012;7(7):e41667. doi: 10.1371/journal.pone.0041667. Epub 2012 Jul 27. [22848561 ]
Target Details
20. Transforming acidic coiled-coil-containing protein 3
General Function:
Not Available
Specific Function:
Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors (By similarity). May be involved in the control of cell growth and differentiation. May contribute to cancer.
Gene Name:
TACC3
Uniprot ID:
Q9Y6A5
Molecular Weight:
90358.865 Da
References
  1. Van Dorst B, Mehta J, Rouah-Martin E, Somers V, De Coen W, Blust R, Robbens J: cDNA phage display as a novel tool to screen for cellular targets of chemical compounds. Toxicol In Vitro. 2010 Aug;24(5):1435-40. doi: 10.1016/j.tiv.2010.04.003. Epub 2010 Apr 18. [20403423 ]
Target Details
21. Translational activator GCN1
General Function:
Translation factor activity, rna binding
Specific Function:
Acts as a translation activator that mediates translational control and perform an EF3-related function on the ribosome by regulating GCN2 protein kinase (EIF2AK1-4) activity.
Gene Name:
GCN1L1
Uniprot ID:
Q92616
Molecular Weight:
292755.02 Da
References
  1. Ito Y, Ito T, Karasawa S, Enomoto T, Nashimoto A, Hase Y, Sakamoto S, Mimori T, Matsumoto Y, Yamaguchi Y, Handa H: Identification of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel target of bisphenol A. PLoS One. 2012;7(12):e50481. doi: 10.1371/journal.pone.0050481. Epub 2012 Dec 5. [23227178 ]
Target Details
22. Tubulin alpha-1C chain
General Function:
Structural molecule activity
Specific Function:
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name:
TUBA1C
Uniprot ID:
Q9BQE3
Molecular Weight:
49894.93 Da
References
  1. Van Dorst B, Mehta J, Rouah-Martin E, Somers V, De Coen W, Blust R, Robbens J: cDNA phage display as a novel tool to screen for cellular targets of chemical compounds. Toxicol In Vitro. 2010 Aug;24(5):1435-40. doi: 10.1016/j.tiv.2010.04.003. Epub 2010 Apr 18. [20403423 ]
Target Details
23. Solute carrier organic anion transporter family member 1B1
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.02 uMCLZD_SLCO1B1_24CellzDirect
AC500.02 uMCLZD_SLCO1B1_24CellzDirect
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
24. Early activation antigen CD69
General Function:
Transmembrane signaling receptor activity
Specific Function:
Involved in lymphocyte proliferation and functions as a signal transmitting receptor in lymphocytes, natural killer (NK) cells, and platelets.
Gene Name:
CD69
Uniprot ID:
Q07108
Molecular Weight:
22559.25 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_SAg_CD69_upBioSeek
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
25. Cytochrome P450 3A4
General Function:
Vitamin d3 25-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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.53 uMCLZD_CYP3A4_48CellzDirect
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
26. 5-hydroxytryptamine receptor 6
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).
Gene Name:
HTR6
Uniprot ID:
P50406
Molecular Weight:
46953.625 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.19 uMNVS_GPCR_h5HT6Novascreen
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
27. 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
AC506.20 uMNVS_ADME_hCYP2C9Novascreen
AC504.24 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
28. Cytochrome P450 2B6
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. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular Weight:
56277.81 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC505.93 uMCLZD_CYP2B6_6CellzDirect
AC504.32 uMCLZD_CYP2B6_48CellzDirect
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
29. 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
AC5010.00 uMNVS_ADME_hCYP3A5Novascreen
AC504.37 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
30. C-C motif chemokine 2
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
CCL2
Uniprot ID:
P13500
Molecular Weight:
11024.87 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_LPS_MCP1_downBioSeek
AC504.44 uMBSK_SAg_MCP1_downBioSeek
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
31. C-X-C motif chemokine 10
General Function:
Receptor binding
Specific Function:
Chemotactic for monocytes and T-lymphocytes. Binds to CXCR3.
Gene Name:
CXCL10
Uniprot ID:
P02778
Molecular Weight:
10880.915 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_BE3C_IP10_downBioSeek
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
32. Transforming growth factor beta-1
General Function:
Type iii transforming growth factor beta receptor binding
Specific Function:
Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner. At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development. At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells.
Gene Name:
TGFB1
Uniprot ID:
P01137
Molecular Weight:
44340.685 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_BE3C_TGFb1_downBioSeek
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
33. Tumor necrosis factor receptor superfamily member 5
General Function:
Ubiquitin protein ligase binding
Specific Function:
Receptor for TNFSF5/CD40LG. Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion.
Gene Name:
CD40
Uniprot ID:
P25942
Molecular Weight:
30618.76 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_SAg_CD40_downBioSeek
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
34. Vascular cell adhesion protein 1
General Function:
Primary amine oxidase activity
Specific Function:
Important in cell-cell recognition. Appears to function in leukocyte-endothelial cell adhesion. Interacts with integrin alpha-4/beta-1 (ITGA4/ITGB1) on leukocytes, and mediates both adhesion and signal transduction. The VCAM1/ITGA4/ITGB1 interaction may play a pathophysiologic role both in immune responses and in leukocyte emigration to sites of inflammation.
Gene Name:
VCAM1
Uniprot ID:
P19320
Molecular Weight:
81275.43 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_hDFCGF_VCAM1_downBioSeek
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
35. 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
AC504.60 uMNVS_ADME_hCYP2C19_ActivatorNovascreen
AC504.80 uMNVS_ADME_hCYP2C19_ActivatorNovascreen
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
36. 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
AC505.01 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
37. Cytochrome P450 1A1
General Function:
Vitamin d 24-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:
CYP1A1
Uniprot ID:
P04798
Molecular Weight:
58164.815 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC505.13 uMNVS_ADME_hCYP1A1Novascreen
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
38. 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
AC505.99 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
39. Adenosine receptor A1
General Function:
Purine nucleoside binding
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
ADORA1
Uniprot ID:
P30542
Molecular Weight:
36511.325 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.01 uMNVS_GPCR_hAdoRA1Novascreen
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
40. 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
AC506.27 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
41. 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
AC507.58 uMNVS_NR_hGRNovascreen
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
42. Delta-type opioid receptor
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular Weight:
40368.235 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.36 uMNVS_GPCR_hOpiate_D1Novascreen
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
43. Mu-type opioid receptor
General Function:
Voltage-gated calcium channel activity
Specific Function:
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC509.55 uMNVS_GPCR_hOpiate_muNovascreen
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 ]