Tmic
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Record Information
Version2.0
Creation Date2013-04-25 07:56:55 UTC
Update Date2014-12-24 20:26:34 UTC
Accession NumberT3D3939
Identification
Common NameTriclosan
ClassSmall Molecule
DescriptionTriclosan 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.
Compound Type
  • Drug
  • Ether
  • Food Toxin
  • Household Toxin
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
2,4,4'-Trichloro-2'-hydroxydiphenyl ether
5-chloro-2-(2, 4-dichlorophenoxy)phenol
5-Chloro-2-(2,4-dichloro-phenoxy)-phenol
DERMAPROT
Irgasan DP 30
Stri-Dex cleansing bar
Triclosanum
Chemical FormulaC12H7Cl3O2
Average Molecular Mass289.542 g/mol
Monoisotopic Mass287.951 g/mol
CAS Registry Number3380-34-5
IUPAC Name5-chloro-2-(2,4-dichlorophenoxy)phenol
Traditional Nametriclosan
SMILESOC1=C(OC2=C(Cl)C=C(Cl)C=C2)C=CC(Cl)=C1
InChI IdentifierInChI=1S/C12H7Cl3O2/c13-7-1-3-11(9(15)5-7)17-12-4-2-8(14)6-10(12)16/h1-6,16H
InChI KeyInChIKey=XEFQLINVKFYRCS-UHFFFAOYSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylethers
Direct ParentDiphenylethers
Alternative Parents
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
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point55-57°C
Boiling Point120°C
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.006 g/LALOGPS
logP5.53ALOGPS
logP4.98ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)7.68ChemAxon
pKa (Strongest Basic)-6.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.46 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity68.69 m³·mol⁻¹ChemAxon
Polarizability25.92 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udi-0490000000-dfb0757bfac1ad90e7a4View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00di-9468000000-8ac957d92fb0baadf85dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-0900000000-58c362c848ddc0ea6b7dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-0900000000-d33e377d9d635f1ce853View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-0900000000-86a497478420de6dd62bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-01ox-1900000000-3924bb3259de13cc0c32View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-01p9-9500000000-1eea0ef329f1eda65753View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000i-9000000000-c0811786de4d26d32f19View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0090000000-1e8f398c881d4511de15View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0090000000-1e8f398c881d4511de15View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000i-0090000000-901f5a26f0a84efe9ab9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000i-0190000000-665be7c9535346c9a726View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0090000000-7662f8b4bedcaffe0a5fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0090000000-62befab95441bb9ec2f0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udj-3980000000-375beaf060515d4bc75bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0090000000-0a0e87adf47e90d9ec1bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-0090000000-40be759356bf6e86ef46View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ikc-2980000000-85ef168fbb3f3d0db80aView in MoNA
MSMass Spectrum (Electron Ionization)splash10-029g-9780000000-d39624d358bdeff3e131View in MoNA
Toxicity Profile
Route of ExposureA study conducted in 2000 demonstrated that low amounts of triclosan can be absorbed through skin and can enter the bloodstream. (1) Triclosan is rapidly absorbed and distributed in the human body (Sandborgh-Englund et al., 2006). Maximum concentrations are reached within three hours after oral intake. However, the metabolism and excretion of the compound is fast.
Mechanism of ToxicityAt in-use concentrations, triclosan acts as a biocide, with multiple cytoplasmic and membrane targets. At lower concentrations, however, triclosan appears bacteriostatic and is seen to target bacteria mainly by inhibiting fatty acid synthesis. Triclosan binds to bacterial enoyl-acyl carrier protein reductase enzyme (ENR), which is encoded by the gene FabI. This binding increases the enzyme's affinity for nicotinamide adenine dinucleotide (NAD+). This results in the formation of a stable ternary complex of ENR-NAD+-triclosan, which is unable to participate in fatty acid synthesis. Fatty acids are necessary for reproducing and building cell membranes. Humans do not have an ENR enzyme, and thus are not affected.
MetabolismTriclosan is prone to phase II metabolism via sulfotransferase and glucuronosyltransferase enzymes (Wang et al., 2004). In humans the resulting conjugates are excreted primarily in urine (Sandborgh-Englund et al., 2006). In one study, after in vivo topical application of a 64.5mM alcoholic solution of [(3)H]triclosan to rat skin, 12% radioactivity was recovered in the faeces, 8% in the carcass 1% in the urine, 30% in the stratum corneum and 26% was rinsed from the skin surface at 24 hours after application. (1) The terminal plasma half life of triclosan is 21 h (Sandborgh-Englund et al., 2006).
Toxicity ValuesOral LD50, Rat: 3700 mg/kg; Dermal LD50, Rabbit: 9300 mg/kg
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesTriclosan is used in a variety of common household products, including soaps, mouthwashes, dish detergents, toothpastes, deodorants, and hand sanitizers. It is also used in health care settings in surgical scrubs and personnel hand washes.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB08604
HMDB IDHMDB61385
PubChem Compound ID5564
ChEMBL IDCHEMBL849
ChemSpider ID5363
KEGG IDC12059
UniProt IDNot Available
OMIM ID
ChEBI ID164200
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkTriclosan
References
Synthesis Reference

Michael A. Mitchell, “Process For Producing Triclosan-Coated Superabsorbents.” U.S. Patent US20120157302, issued June 21, 2012.

MSDSLink
General References
  1. Moss T, Howes D, Williams FM: Percutaneous penetration and dermal metabolism of triclosan (2,4, 4'-trichloro-2'-hydroxydiphenyl ether). Food Chem Toxicol. 2000 Apr;38(4):361-70. [10722890 ]
  2. Russell AD: Whither triclosan? J Antimicrob Chemother. 2004 May;53(5):693-5. Epub 2004 Apr 8. [15073159 ]
  3. Heath RJ, Rubin JR, Holland DR, Zhang E, Snow ME, Rock CO: Mechanism of triclosan inhibition of bacterial fatty acid synthesis. J Biol Chem. 1999 Apr 16;274(16):11110-4. [10196195 ]
  4. Fan F, Yan K, Wallis NG, Reed S, Moore TD, Rittenhouse SF, DeWolf WE Jr, Huang J, McDevitt D, Miller WH, Seefeld MA, Newlander KA, Jakas DR, Head MS, Payne DJ: Defining and combating the mechanisms of triclosan resistance in clinical isolates of Staphylococcus aureus. Antimicrob Agents Chemother. 2002 Nov;46(11):3343-7. [12384334 ]
  5. Fang JL, Stingley RL, Beland FA, Harrouk W, Lumpkins DL, Howard P: Occurrence, efficacy, metabolism, and toxicity of triclosan. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2010 Jul;28(3):147-71. doi: 10.1080/10590501.2010.504978. [20859822 ]
  6. ON THE FATE OF TRICLOSAN IN HUMANS [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

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
TypeValueAssay TypeAssay Source
AC502.97 uMATG_PXRE_CISAttagene
AC503.27 uMNVS_NR_hPXRNovascreen
References
  1. Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [16054614 ]
  2. 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:
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.29 uMNVS_NR_hARNovascreen
AC505.91 uMOT_AR_ARSRC1_0480Odyssey Thera
AC508.80 uMNVS_NR_hARNovascreen
References
  1. 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 ]
  2. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.06 uMNot AvailableBindingDB 8726
IC500.4 uMNot AvailableBindingDB 8726
References
  1. 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
  1. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5053.5 uMNot AvailableBindingDB 8726
Dissociation144 uMNot AvailableBindingDB 8726
References
  1. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.03 uMCLZD_CYP2B6_24CellzDirect
AC503.46 uMCLZD_CYP2B6_6CellzDirect
AC500.03 uMCLZD_CYP2B6_24CellzDirect
AC501.77 uMCLZD_CYP2B6_48CellzDirect
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.30 uMNVS_TR_hNETNovascreen
AC500.32 uMNVS_TR_hNETNovascreen
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 ]
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
CCL2
Uniprot ID:
P13500
Molecular Weight:
11024.87 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_KF3CT_MCP1_upBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Receptor binding
Specific Function:
Chemotactic for monocytes and T-lymphocytes. Binds to CXCR3.
Gene Name:
CXCL10
Uniprot ID:
P02778
Molecular Weight:
10880.915 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_hDFCGF_IP10_downBioSeek
AC501.48 uMBSK_KF3CT_IP10_upBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_hDFCGF_CollagenIII_upBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_BE3C_IL1a_upBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_hDFCGF_MMP1_upBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_hDFCGF_TIMP1_upBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_hDFCGF_PAI1_upBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.38 uMNVS_ADME_hCYP2C19Novascreen
AC509.30 uMNVS_ADME_hCYP2C19Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.39 uMCLZD_CYP3A4_6CellzDirect
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 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_3C_Eselectin_downBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_3C_hLADR_downBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_hDFCGF_MCSF_downBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_SM3C_uPAR_upBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Primary amine oxidase activity
Specific Function:
Important in cell-cell recognition. Appears to function in leukocyte-endothelial cell adhesion. Interacts with integrin alpha-4/beta-1 (ITGA4/ITGB1) on leukocytes, and mediates both adhesion and signal transduction. The VCAM1/ITGA4/ITGB1 interaction may play a pathophysiologic role both in immune responses and in leukocyte emigration to sites of inflammation.
Gene Name:
VCAM1
Uniprot ID:
P19320
Molecular Weight:
81275.43 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_4H_VCAM1_downBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC505.36 uMNVS_ADME_hCYP2C9Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
AC505.69 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 ]
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular Weight:
40368.235 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.36 uMNVS_GPCR_hOpiate_D1Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.58 uMNVS_ENZ_hBACENovascreen
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 ]
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
AC506.63 uMNVS_NR_hPPARgNovascreen
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 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.31 uMATG_BRE_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 ]