Triclosan
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Basic Info
| Common Name | Triclosan(F05151) |
| 2D Structure | |
| Description | Triclosan is an antibacterial and antifungal agent. It is a polychloro phenoxy phenol. Though many consumer products contain triclosan, according to the Food and Drug Administration (FDA) at the present time there is no evidence that triclosan in personal care products provides an extra benefit to health beyond its anti-gingivitis effect in toothpaste. The FDA does not recommend changing consumer use of triclosan containing products one way or the other due to currently insufficient safety evidence. Studies by the Environmental Protection Agency (EPA) found triclosan to be an effective antibacterial. Triclosan safety is currently under review by the FDA and Health Canada. |
| FRCD ID | F05151 |
| CAS Number | 3380-34-5 |
| PubChem CID | 5564 |
| Formula | C12H7Cl3O2 |
| IUPAC Name | 5-chloro-2-(2,4-dichlorophenoxy)phenol |
| InChI Key | XEFQLINVKFYRCS-UHFFFAOYSA-N |
| InChI | InChI=1S/C12H7Cl3O2/c13-7-1-3-11(9(15)5-7)17-12-4-2-8(14)6-10(12)16/h1-6,16H |
| Canonical SMILES | C1=CC(=C(C=C1Cl)O)OC2=C(C=C(C=C2)Cl)Cl |
| Isomeric SMILES | C1=CC(=C(C=C1Cl)O)OC2=C(C=C(C=C2)Cl)Cl |
| Wikipedia | Triclosan |
| Synonyms |
5-CHLORO-2-(2,4-DICHLOROPHENOXY)PHENOL
triclosan
3380-34-5
Irgasan
2,4,4'-Trichloro-2'-hydroxydiphenyl ether
Cloxifenolum
Triclosanum
Irgasan DP300
Stri-Dex Face Wash
Aquasept
|
| Classifies |
Predicted: Pollutant
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Benzene and substituted derivatives |
| Subclass | Diphenylethers |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Diphenylethers |
| Alternative Parents | |
| Molecular Framework | Aromatic homomonocyclic compounds |
| Substituents | Diphenylether - Diaryl ether - Phenoxy compound - Phenol ether - 1,3-dichlorobenzene - 3-chlorophenol - 3-halophenol - 1-hydroxy-4-unsubstituted benzenoid - 1-hydroxy-2-unsubstituted benzenoid - Phenol - Chlorobenzene - Halobenzene - Aryl chloride - Aryl halide - Ether - Organic oxygen compound - Organohalogen compound - Organochloride - Organooxygen compound - Hydrocarbon derivative - Aromatic homomonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether group. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 289.536 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 2 |
| Complexity | 252 |
| Monoisotopic Mass | 287.951 |
| Exact Mass | 287.951 |
| XLogP | 5 |
| Formal Charge | 0 |
| Heavy Atom Count | 17 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9653 |
| Human Intestinal Absorption | HIA+ | 0.9941 |
| Caco-2 Permeability | Caco2+ | 0.8461 |
| P-glycoprotein Substrate | Non-substrate | 0.7545 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8094 |
| Non-inhibitor | 0.8656 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8261 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.9013 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7708 |
| CYP450 2D6 Substrate | Non-substrate | 0.8807 |
| CYP450 3A4 Substrate | Non-substrate | 0.6205 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.8668 |
| CYP450 2C9 Inhibitor | Inhibitor | 0.6565 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8851 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.8943 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8979 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.7195 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9060 |
| Non-inhibitor | 0.8289 | |
| AMES Toxicity | Non AMES toxic | 0.9413 |
| Carcinogens | Non-carcinogens | 0.7864 |
| Fish Toxicity | High FHMT | 0.9404 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9968 |
| Honey Bee Toxicity | High HBT | 0.7538 |
| Biodegradation | Not ready biodegradable | 0.9368 |
| Acute Oral Toxicity | III | 0.7936 |
| Carcinogenicity (Three-class) | Non-required | 0.5116 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -4.5225 | LogS |
| Caco-2 Permeability | 1.5713 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.0589 | LD50, mol/kg |
| Fish Toxicity | -0.4197 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 2.0624 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Triclosan Is an Aminoglycoside Adjuvant for Eradication of Pseudomonas aeruginosaBiofilms. | Antimicrob Agents Chemother | 2018 May 25 | 29661867 |
| Sorption and bioaccumulation behavior of multi-class hydrophobic organiccontaminants in a tropical marine food web. | Chemosphere | 2018 May | 29428515 |
| Determination of household and industrial chemicals, personal care products andhormones in leafy and root vegetables by liquid chromatography-tandem massspectrometry. | J Chromatogr A | 2018 Jan 19 | 29229332 |
| Study of the Interactions Between Bacteriophage phiIPLA-RODI and Four ChemicalDisinfectants for the Elimination of Staphylococcus aureus Contamination. | Viruses | 2018 Feb 28 | 29495568 |
| Removal of novel antiandrogens identified in biological effluents of domesticwastewater by activated carbon. | Sci Total Environ | 2017 Oct 1 | 28407587 |
| Salting-out-enhanced ionic liquid microextraction with a dual-role solvent forsimultaneous determination of trace pollutants with a wide polarity range inaqueous samples. | Anal Bioanal Chem | 2017 Nov | 28871466 |
| Inhibitory effects of 3,3'-diindolylmethane on epithelial-mesenchymal transition induced by endocrine disrupting chemicals in cellular and xenograft mouse models of breast cancer. | Food Chem Toxicol | 2017 Nov | 28844962 |
| Exchange of polar lipids from adults to neonates in Daphnia magna: Perturbations in sphingomyelin allocation by dietary lipids and environmental toxicants. | PLoS One | 2017 May 24 | 28542405 |
| Effects of exposure to quaternary-ammonium-based biocides on antimicrobialsusceptibility and tolerance to physical stresses in bacteria from organic foods. | Food Microbiol | 2017 May | 28040182 |
| Algae-mediated removal of selected pharmaceutical and personal care products(PPCPs) from Lake Mead water. | Sci Total Environ | 2017 Mar 1 | 28089530 |
| Cytochrome P450-mediated metabolism of triclosan attenuates its cytotoxicity in hepatic cells. | Arch Toxicol | 2017 Jun | 27896399 |
| Effect of soil biochar concentration on the mitigation of emerging organiccontaminant uptake in lettuce. | J Hazard Mater | 2017 Feb 5 | 27143287 |
| Diverging temporal trends of human exposure to bisphenols and plastizisers, such as phthalates, caused by substitution of legacy EDCs? | Environ Res | 2017 Feb | 27898309 |
| Biocide Tolerance and Antibiotic Resistance in Salmonella Isolates from HenEggshells. | Foodborne Pathog Dis | 2017 Feb | 27841937 |
| Household triclosan and triclocarban effects on the infant and maternalmicrobiome. | EMBO Mol Med | 2017 Dec | 29030459 |
| In Vitro Evaluation of Mitochondrial Function and Estrogen Signaling in CellLines Exposed to the Antiseptic Cetylpyridinium Chloride. | Environ Health Perspect | 2017 Aug 22 | 28885978 |
| Uptake and elimination kinetics of the biocide triclosan and the synthetic musks galaxolide and tonalide in the earthworm Dendrobaena veneta when exposed tosewage sludge. | Environ Toxicol Chem | 2017 Aug | 28079271 |
| Characterization of biocide-tolerant bacteria isolated from cheese and dairysmall-medium enterprises. | Food Microbiol | 2017 Apr | 27889169 |
| Is Triclosan a neurotoxic agent? | J Toxicol Environ Health B Crit Rev | 2017 | 28339349 |
| Removal of trimethoprim, sulfamethoxazole, and triclosan by the green algaNannochloris sp. | J Hazard Mater | 2016 Sep 5 | 27179202 |
Targets
- 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
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:
- Norepinephrine:sodium symporter activity
- Specific Function:
- Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name:
- SLC6A2
- Uniprot ID:
- P23975
- Molecular Weight:
- 69331.42 Da
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 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
References
- Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [16054614 ]
- 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
References
- Christen V, Crettaz P, Oberli-Schrammli A, Fent K: Some flame retardants and the antimicrobials triclosan and triclocarban enhance the androgenic activity in vitro. Chemosphere. 2010 Nov;81(10):1245-52. doi: 10.1016/j.chemosphere.2010.09.031. Epub 2010 Oct 12. [20943248 ]
- General Function:
- Prostaglandin-e2 9-reductase activity
- Specific Function:
- NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E2 to prostaglandin F2-alpha. Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione.
- Gene Name:
- CBR1
- Uniprot ID:
- P16152
- Molecular Weight:
- 30374.73 Da
References
- Zimmermann TJ, Niesen FH, Pilka ES, Knapp S, Oppermann U, Maier ME: Discovery of a potent and selective inhibitor for human carbonyl reductase 1 from propionate scanning applied to the macrolide zearalenone. Bioorg Med Chem. 2009 Jan 15;17(2):530-6. doi: 10.1016/j.bmc.2008.11.076. Epub 2008 Dec 6. [19097799 ]
- 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
- Paul KB, Thompson JT, Simmons SO, Vanden Heuvel JP, Crofton KM: Evidence for triclosan-induced activation of human and rodent xenobiotic nuclear receptors. Toxicol In Vitro. 2013 Oct;27(7):2049-60. doi: 10.1016/j.tiv.2013.07.008. Epub 2013 Jul 27. [23899473 ]
- General Function:
- Identical protein binding
- Specific Function:
- Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
- Gene Name:
- TTR
- Uniprot ID:
- P02766
- Molecular Weight:
- 15886.88 Da
References
- Gupta S, Chhibber M, Sinha S, Surolia A: Design of mechanism-based inhibitors of transthyretin amyloidosis: studies with biphenyl ethers and new structural templates. J Med Chem. 2007 Nov 15;50(23):5589-99. Epub 2007 Oct 19. [17948976 ]
- 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
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:
- Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.
- Gene Name:
- IL1A
- Uniprot ID:
- P01583
- Molecular Weight:
- 30606.29 Da
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:
- Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity.
- Gene Name:
- MMP1
- Uniprot ID:
- P03956
- Molecular Weight:
- 54006.61 Da
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:
- Serine-type endopeptidase inhibitor activity
- Specific Function:
- Serine protease inhibitor. This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, protein C and matriptase-3/TMPRSS7. Its rapid interaction with PLAT may function as a major control point in the regulation of fibrinolysis.
- Gene Name:
- SERPINE1
- Uniprot ID:
- P05121
- Molecular Weight:
- 45059.695 Da
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:
- 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
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:
- 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
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:
- Transmembrane signaling receptor activity
- Specific Function:
- Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with PSGL1/SELPLG. May have a role in capillary morphogenesis.
- Gene Name:
- SELE
- Uniprot ID:
- P16581
- Molecular Weight:
- 66654.575 Da
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:
- Peptidase activity
- Specific Function:
- Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.
- Gene Name:
- BACE1
- Uniprot ID:
- P56817
- Molecular Weight:
- 55710.28 Da
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
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:
- Urokinase plasminogen activator receptor activity
- Specific Function:
- Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.
- Gene Name:
- PLAUR
- Uniprot ID:
- Q03405
- Molecular Weight:
- 36977.62 Da
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:
- 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
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. 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
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:
- 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
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:
- 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
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:
- Transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity
- Specific Function:
- Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor-regulated SMAD (R-SMAD). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. May act synergistically with SMAD4 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression.
- Gene Name:
- SMAD1
- Uniprot ID:
- Q15797
- Molecular Weight:
- 52259.72 Da
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 ]
- Gene Name:
- CCL2
- Uniprot ID:
- P13500
- Molecular Weight:
- 11024.87 Da
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:
- Platelet-derived growth factor binding
- Specific Function:
- Collagen type III occurs in most soft connective tissues along with type I collagen. Involved in regulation of cortical development. Is the major ligand of GPR56 in the developing brain and binding to GPR56 inhibits neuronal migration and activates the RhoA pathway by coupling GPR56 to GNA13 and possibly GNA12.
- Gene Name:
- COL3A1
- Uniprot ID:
- P02461
- Molecular Weight:
- 138564.005 Da
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:
- Protease binding
- Specific Function:
- Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling. Mediates erythropoiesis in vitro; but, unlike IL3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors.
- Gene Name:
- TIMP1
- Uniprot ID:
- P01033
- Molecular Weight:
- 23170.64 Da
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:
- Peptide antigen binding
- Specific Function:
- Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
- Gene Name:
- HLA-DRA
- Uniprot ID:
- P01903
- Molecular Weight:
- 28606.685 Da
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 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
- 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 ]