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Apigenin (T3D4888)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (9)XML
Targets (9)
Record Information
Version2.0
Creation Date2014-09-11 05:20:57 UTC
Update Date2014-12-24 20:26:59 UTC
Accession NumberT3D4888
Identification
Common NameApigenin
ClassSmall Molecule
DescriptionApigenin is a plant-derived flavonoid that has significant promise as a skin cancer chemopreventive agent. Apigenin inhibits the expression of involucrin (hINV), a marker of keratinocyte differentiation, is increased by differentiating agents via a protein kinase Cdelta (PKCdelta), Ras, MEKK1, MEK3 cascade that increases AP1 factor level and AP1 factor binding to DNA elements in the hINV promoter. Apigenin suppresses the 12-O-tetradeconylphorbol-13-acetate-dependent increase in AP1 factor expression and binding to the hINV promoter and the increase in hINV promoter activity. Apigenin also inhibits the increase in promoter activity observed following overexpression of PKCdelta, constitutively active Ras, or MEKK1. The suppression of PKCdelta activity is associated with reduced phosphorylation of PKCdelta-Y311. Activation of hINV promoter activity by the green tea polyphenol, (-)-epigellocathecin-3-gallate, is also inhibited by apigenin, suggesting that the two chemopreventive agents can produce opposing actions in keratinocytes. (1). Apigenin, a flavone abundantly found in fruits and vegetables, exhibits antiproliferative, anti-inflammatory, and antimetastatic activities through poorly defined mechanisms. This flavonoid provides selective activity to promote caspase-dependent-apoptosis of leukemia cells and uncover an essential role of PKCdelta during the induction of apoptosis by apigenin. (2). Apigenin markedly induces the expression of death receptor 5 (DR5) and synergistically acts with exogenous soluble recombinant human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to induce apoptosis in malignant tumor cells. On the other hand, apigenin-mediated induction of DR5 expression is not observed in normal human peripheral blood mononuclear cells. Moreover, apigenin does not sensitize normal human peripheral blood mononuclear cells to TRAIL-induced apoptosis. (3).
Compound Type
  • Drug
  • Ester
  • Food Toxin
  • Household Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
2-(p-Hydroxyphenyl)-5,7-dihydroxychromone
4',5,7-Trihydroxy-Flavone
4,5, 7-Trihydroxyflavone
5,7-Dihydroxy-2-(4-hydroxyphenyl)-4-benzopyrone
5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
Apigenol
Chamomile
Spigenin
Versulin
Chemical FormulaC15H10O5
Average Molecular Mass270.237 g/mol
Monoisotopic Mass270.053 g/mol
CAS Registry Number520-36-5
IUPAC Name5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
Traditional Namechamomile
SMILESOC1=CC=C(C=C1)C1=CC(=O)C2=C(O)C=C(O)C=C2O1
InChI IdentifierInChI=1S/C15H10O5/c16-9-3-1-8(2-4-9)13-7-12(19)15-11(18)5-10(17)6-14(15)20-13/h1-7,16-18H
InChI KeyInChIKey=KZNIFHPLKGYRTM-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as flavones. These are flavonoids with a structure based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one).
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassFlavonoids
Sub ClassFlavones
Direct ParentFlavones
Alternative Parents
Substituents
  • 4'-hydroxyflavonoid
  • 5-hydroxyflavonoid
  • 7-hydroxyflavonoid
  • Flavone
  • Hydroxyflavonoid
  • Chromone
  • Benzopyran
  • 1-benzopyran
  • 1-hydroxy-4-unsubstituted benzenoid
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Pyranone
  • Monocyclic benzene moiety
  • Benzenoid
  • Pyran
  • Vinylogous acid
  • Heteroaromatic compound
  • Organoheterocyclic compound
  • Oxacycle
  • Organic oxygen compound
  • Organooxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point347.5 °C
Boiling PointNot Available
SolubilityNot Available
LogP3.02
Predicted Properties
PropertyValueSource
Water Solubility0.12 g/LALOGPS
logP3.07ALOGPS
logP2.71ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)6.57ChemAxon
pKa (Strongest Basic)-5.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area86.99 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity72.91 m³·mol⁻¹ChemAxon
Polarizability26.78 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-00di-0000900000-b6d7fc88c039e719d1642014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00di-0433900000-b411d851fccc9f228d842017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-03xv-1913500000-be46740b1210f9e106ee2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00di-0000900000-b6d7fc88c039e719d1642017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00fu-0390000000-746c7fa7b11e53e272352017-07-27View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-0229-4222900000-fe657c625506c272a0362017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF 30V, Negativesplash10-014i-0940000000-eb8b08c7beca627dc7282017-08-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF , Negativesplash10-014i-0090000000-3fea3046af52ea21ae282017-08-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF 30V, Negativesplash10-014i-0940000000-eb8b08c7beca627dc7282017-09-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF , Negativesplash10-014i-0090000000-3fea3046af52ea21ae282017-09-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - DI-ESI-qTof , Negativesplash10-014i-0890000000-c8366acac0c0d42ae2e82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0090000000-0f608530bf761944dbf32017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0090000000-0c659ac43b543480168b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0690000000-e19eed49b8311d9cd3392017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0910000000-57a56bfe2cce55357a112017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0900000000-b8799a618cff0ac84ddb2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0490000000-f9a416c79166c84ca7732017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0900000000-1499c7f2bceeb3e13f522017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0490000000-413a7da79773bc92a1122017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0090000000-8f4d30104539ae85cd502017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0290000000-32e8793c17b364eee1272017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0uea-0900000000-52147353f7af35162dab2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-014i-0090000000-7a9b77ceb393c92394122017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-00vi-0290000000-c9cb9331a28763da83a82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-TOF , negativesplash10-014i-0940000000-eb8b08c7beca627dc7282017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Negativesplash10-014i-0900000000-072fb056044b71de29672021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-014i-0900000000-35e54babc71b9d557d7b2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-014i-0090000000-d0d7979a02697bd4d8fd2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Negativesplash10-014i-0290000000-832bf870255aa3b016172021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Negativesplash10-0uea-0900000000-52147353f7af35162dab2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-00am-0960000000-155c48a2761e351e02e32021-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, H2O, predicted)Not Available2022-08-22View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB07352
HMDB IDHMDB02124
PubChem Compound ID5280443
ChEMBL IDCHEMBL28
ChemSpider ID4444100
KEGG IDC01477
UniProt IDNot Available
OMIM ID
ChEBI ID18388
BioCyc IDCPD-431
CTD IDD047310
Stitch IDNot Available
PDB IDAGI
ACToR IDNot Available
Wikipedia LinkApigenin
References
Synthesis ReferenceChen, Xin; Li, Ping. Processes for the preparation of apigenin from naringin via rhoifolin or naringenin intermediate. Faming Zhuanli Shenqing Gongkai Shuomingshu (2005), 9 pp
MSDSLink
General References
  1. Balasubramanian S, Zhu L, Eckert RL: Apigenin inhibition of involucrin gene expression is associated with a specific reduction in phosphorylation of protein kinase Cdelta Tyr311. J Biol Chem. 2006 Nov 24;281(47):36162-72. Epub 2006 Sep 18. [16982614 ]
  2. Vargo MA, Voss OH, Poustka F, Cardounel AJ, Grotewold E, Doseff AI: Apigenin-induced-apoptosis is mediated by the activation of PKCdelta and caspases in leukemia cells. Biochem Pharmacol. 2006 Sep 14;72(6):681-92. Epub 2006 Jul 17. [16844095 ]
  3. Horinaka M, Yoshida T, Shiraishi T, Nakata S, Wakada M, Sakai T: The dietary flavonoid apigenin sensitizes malignant tumor cells to tumor necrosis factor-related apoptosis-inducing ligand. Mol Cancer Ther. 2006 Apr;5(4):945-51. [16648565 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. 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
References
  1. Allen SW, Mueller L, Williams SN, Quattrochi LC, Raucy J: The use of a high-volume screening procedure to assess the effects of dietary flavonoids on human cyp1a1 expression. Drug Metab Dispos. 2001 Aug;29(8):1074-9. [11454723 ]
Target Details
2. 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
AC500.0554 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 ]
  2. 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 ]
Target Details
3. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.252 uMTox21_AhRTox21/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
4. 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
AC501.55 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC502.83 uMATG_ERa_TRANSAttagene
AC502.55 uMATG_ERE_CISAttagene
AC500.272 uMNVS_NR_hERNovascreen
AC503.2 uMOT_ER_ERaERa_0480Odyssey Thera
AC504.53 uMOT_ERa_EREGFP_0120Odyssey Thera
AC503.47 uMOT_ERa_EREGFP_0480Odyssey Thera
AC508.28 uMTox21_ERa_BLA_Agonist_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 ]
  2. Seo HS, DeNardo DG, Jacquot Y, Laios I, Vidal DS, Zambrana CR, Leclercq G, Brown PH: Stimulatory effect of genistein and apigenin on the growth of breast cancer cells correlates with their ability to activate ER alpha. Breast Cancer Res Treat. 2006 Sep;99(2):121-34. Epub 2006 Mar 16. [16541309 ]
Target Details
5. 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
AC501.53 uMOT_ER_ERaERb_0480Odyssey Thera
AC501.22 uMOT_ER_ERbERb_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 ]
  2. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA: Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 1998 Oct;139(10):4252-63. [9751507 ]
Target Details
6. ATPase family AAA domain-containing protein 5
General Function:
Atp binding
Specific Function:
Involved in DNA damage response. Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis. Modulates the RAD9A interaction with BCL2 and thereby induces DNA damages-induced apoptosis.
Gene Name:
ATAD5
Uniprot ID:
Q96QE3
Molecular Weight:
207568.185 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.37 uMTox21_ELG1_LUC_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
7. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.4 uMTox21_PPARg_BLA_Agonist_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
8. Hypoxia-inducible factor 1-alpha
General Function:
Ubiquitin protein ligase binding
Specific Function:
Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.
Gene Name:
HIF1A
Uniprot ID:
Q16665
Molecular Weight:
92669.595 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC505.61 uMATG_HIF1a_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
9. Cytochrome P450 1B1
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, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression.
Gene Name:
CYP1B1
Uniprot ID:
Q16678
Molecular Weight:
60845.33 Da
References
  1. Shimada T, Tanaka K, Takenaka S, Murayama N, Martin MV, Foroozesh MK, Yamazaki H, Guengerich FP, Komori M: Structure-function relationships of inhibition of human cytochromes P450 1A1, 1A2, 1B1, 2C9, and 3A4 by 33 flavonoid derivatives. Chem Res Toxicol. 2010 Dec 20;23(12):1921-35. doi: 10.1021/tx100286d. [21053930 ]