Di(2-ethylhexyl)phthalate (T3D0076)
| Record Information | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Version | 2.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Creation Date | 2009-03-06 18:58:02 UTC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Update Date | 2014-12-24 20:21:03 UTC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Accession Number | T3D0076 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Identification | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Common Name | Di(2-ethylhexyl)phthalate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Class | Small Molecule | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | Di(2-ethylhexyl) phthlate (DEHP) is a manufactured chemical that is commonly added to plastics to make them flexible. DEHP exposure is generally low and not harmful, but increased exposures resulting from intravenous fluids delivered through plastic tubing or ingesting contaminated foods or water may have toxic effects. This is of particular concern since DEHP is known to leach into liquid that come in contact with DEHP containing plastic. (6, 7) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Compound Type |
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| Chemical Structure |  | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Synonyms |
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| Chemical Formula | C24H38O4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Average Molecular Mass | 390.556 g/mol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monoisotopic Mass | 390.277 g/mol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAS Registry Number | 117-81-7 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| IUPAC Name | 1,2-bis(2-ethylhexyl) benzene-1,2-dicarboxylate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Traditional Name | etalon | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| SMILES | CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Identifier | InChI=1S/C24H38O4/c1-5-9-13-19(7-3)17-27-23(25)21-15-11-12-16-22(21)24(26)28-18-20(8-4)14-10-6-2/h11-12,15-16,19-20H,5-10,13-14,17-18H2,1-4H3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=BJQHLKABXJIVAM-UHFFFAOYSA-N | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Chemical Taxonomy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Super Class | Benzenoids | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Class | Benzene and substituted derivatives | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sub Class | Benzoic acids and derivatives | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Direct Parent | Benzoic acid esters | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative Parents | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Substituents |
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| Molecular Framework | Aromatic homomonocyclic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External Descriptors |
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| Biological Properties | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status | Detected and Not Quantified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Origin | Exogenous | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cellular Locations |
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| Biofluid Locations | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tissue Locations | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pathways | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Applications | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological Roles | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Chemical Roles | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Physical Properties | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| State | Liquid | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Appearance | Coloress liquid. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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| Spectra | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Spectra |
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| Toxicity Profile | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Route of Exposure | Oral (8) ; inhalation (8) ; dermal (8) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mechanism of Toxicity | Monoethylhexylphthalate (MEHP), one of the major metabolites of DEHP, induces peroxisome proliferation by activating peroxisome proliferator activated receptors. This is believed to increase production of hydrogen peroxide by peroxisomes and enhance cell proliferation, leading to hepatotoxic and carcinogenic effects. MEHP is also believed to exhibit testicular toxicity by targeting and damaging the Sertoli cells. DEHP may act as an antiandrogen during a critical stage of reproductive tract differentiation by reducing testosterone in fetal males, hindering development. (6, 1) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Metabolism | DEHP is mainly absorbed via ingestion. It is hydrolyzed in the small intestine and absorbed as monoethylhexylphthalate (MEHP) and 2-ethylhexanol, then likely distributed to the adipose tissues and kidneys. MEHP is further metabolized via numerous oxidative reactions, resulting in the formation of 30 or more metabolites, some of which can be conjugated with glucuronic acid for excretion. Oxidation of 2-ethylhexanol primarily yields 2-ethylhexanoic acid and several keto acid derivatives. Most DEHP metabolites are excreted in the urine as glucuronide conjugates, while unmetabolized DEHP is excreted in the faeces. (6) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Toxicity Values | LD50: 33.9 g/kg (Oral, Rabbit) (3) LD50: 10 g/kg (Dermal, Guinea pig) (3) LD50: 30.7 g/kg (Intraperitoneal, Rat) (3) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lethal Dose | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Carcinogenicity (IARC Classification) | 2B, possibly carcinogenic to humans. (5) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Uses/Sources | DEHP is present in plastic products such as wall coverings, tablecloths, floor tiles, furniture upholstery, shower curtains, garden hoses, swimming pool liners, rainwear, baby pants, dolls, some toys, shoes, automobile upholstery and tops, packaging film and sheets, sheathing for wire and cable, medical tubing, and blood storage bags. (6) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Minimum Risk Level | Intermediate Oral: 0.1 mg/kg/day (4) Chronic Oral: 0.06 mg/kg/day (4) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Health Effects | Chronic and/or high levels of DEHP exposure may cause reproductive and developmental damage. This includes damaged sperm, delayed sexual maturity, and deficiencies in the development of male babies. DEHP may also cause liver and kidney damage, and is potentially carcinogenic. (6, 7) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Symptoms | Phthalate esters are endocrine disruptors and can cause a number of developmental malformations termed 'phthalate syndrome'. (2) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Treatment | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Normal Concentrations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abnormal Concentrations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External Links | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DrugBank ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HMDB ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PubChem Compound ID | 8343 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChEMBL ID | CHEMBL1242017 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChemSpider ID | 21106505 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| KEGG ID | C03690 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| UniProt ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| OMIM ID | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChEBI ID | 17747 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BioCyc ID | BIS2-ETHYLHEXYLPHTHALATE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CTD ID | D004051 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Stitch ID | Di(2-ethylhexyl)phthalate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PDB ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ACToR ID | 617 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikipedia Link | Bis(2-ethylhexyl)phthalate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| References | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MSDS | T3D0076.pdf | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| General References |
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| Gene Regulation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Up-Regulated Genes |
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| Down-Regulated Genes |
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Targets
- 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
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| AC50 | 5.56 uM | NVS_NR_hPXR | Novascreen |
References
- Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [16054614 ]
- 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 ]
- 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 ]
- 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
- Lapinskas PJ, Brown S, Leesnitzer LM, Blanchard S, Swanson C, Cattley RC, Corton JC: Role of PPARalpha in mediating the effects of phthalates and metabolites in the liver. Toxicology. 2005 Feb 1;207(1):149-63. [15590130 ]
- 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 ]
- 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
- Lapinskas PJ, Brown S, Leesnitzer LM, Blanchard S, Swanson C, Cattley RC, Corton JC: Role of PPARalpha in mediating the effects of phthalates and metabolites in the liver. Toxicology. 2005 Feb 1;207(1):149-63. [15590130 ]
- 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 ]
- 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
- Lapinskas PJ, Brown S, Leesnitzer LM, Blanchard S, Swanson C, Cattley RC, Corton JC: Role of PPARalpha in mediating the effects of phthalates and metabolites in the liver. Toxicology. 2005 Feb 1;207(1):149-63. [15590130 ]
- 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 ]
- 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
- Mankidy R, Wiseman S, Ma H, Giesy JP: Biological impact of phthalates. Toxicol Lett. 2013 Feb 13;217(1):50-8. doi: 10.1016/j.toxlet.2012.11.025. Epub 2012 Dec 7. [23220035 ]
- 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
References
- Takeuchi S, Iida M, Kobayashi S, Jin K, Matsuda T, Kojima H: Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor. Toxicology. 2005 Jun 1;210(2-3):223-33. [15840436 ]
- 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
References
- Takeuchi S, Iida M, Kobayashi S, Jin K, Matsuda T, Kojima H: Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor. Toxicology. 2005 Jun 1;210(2-3):223-33. [15840436 ]
- 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
References
- 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 ]
- 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
- 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 ]
- 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
- 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 ]
- General Function:
- Sulfotransferase activity
- Specific Function:
- Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfonation of steroids and bile acids in the liver and adrenal glands.
- Gene Name:
- SULT2A1
- Uniprot ID:
- Q06520
- Molecular Weight:
- 33779.57 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| AC50 | 0.48 uM | CLZD_SULT2A1_6 | CellzDirect |
| AC50 | 0.48 uM | CLZD_SULT2A1_6 | CellzDirect |
References
- 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 ]
- 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
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| AC50 | 5.88 uM | CLZD_CYP2B6_6 | CellzDirect |
| AC50 | 3.97 uM | CLZD_CYP2B6_24 | CellzDirect |
| AC50 | 1.38 uM | CLZD_CYP2B6_48 | CellzDirect |
References
- 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 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone development. Required for normal male and female fertility. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. Plays a role in lipoprotein clearance.
- Gene Name:
- CSF1
- Uniprot ID:
- P09603
- Molecular Weight:
- 60178.885 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| AC50 | 1.48 uM | BSK_hDFCGF_MCSF_down | BioSeek |
References
- 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 ]
- General Function:
- Zinc ion binding
- Specific Function:
- May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.
- Gene Name:
- MMP9
- Uniprot ID:
- P14780
- Molecular Weight:
- 78457.51 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| AC50 | 1.48 uM | BSK_KF3CT_MMP9_down | BioSeek |
References
- 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 ]
- General Function:
- Cytokine activity
- Specific Function:
- Cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response. Chemotactic for activated T-cells. Binds to CXCR3.
- Gene Name:
- CXCL9
- Uniprot ID:
- Q07325
- Molecular Weight:
- 14018.72 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| AC50 | 4.44 uM | BSK_hDFCGF_MIG_down | BioSeek |
References
- 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 ]
- General Function:
- Cholesterol binding
- Specific Function:
- Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
- Gene Name:
- TSPO
- Uniprot ID:
- P30536
- Molecular Weight:
- 18827.81 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| AC50 | 8.62 uM | NVS_MP_hPBR | Novascreen |
| AC50 | 8.90 uM | NVS_MP_hPBR | Novascreen |
References
- 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 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Recruited to promoters via its interaction with BAZ1B/WSTF which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.
- Gene Name:
- VDR
- Uniprot ID:
- P11473
- Molecular Weight:
- 48288.64 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| AC50 | 9.29 uM | ATG_VDRE_CIS | Attagene |
References
- 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 ]