Tmic
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Record Information
Version2.0
Creation Date2009-03-06 18:58:10 UTC
Update Date2014-12-24 20:21:13 UTC
Accession NumberT3D0145
Identification
Common NameParathion
ClassSmall Molecule
DescriptionParathion is a highly toxic cholinesterase inhibitor that is used as an acaricide and as an insecticide, generally applied by spraying, most often to cotton, rice, and fruit trees. Also called parathion-ethyl or diethyl parathion, parathion is an organophosphate compound. As parathion is highly toxic to non-target organisms, its use is banned or restricted in many areas. (17)
Compound Type
  • Aromatic Hydrocarbon
  • Ester
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Organophosphate
  • Pesticide
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Alkron
Alleron
Aphamite
Aqua 9-Parathion
Aralo
Bladan
Bladen
Corothion
Corthione
Danthion
Deoxynucleoside 5'-triphosphate
Diethyl 4-nitrophenyl phosphorothionate
Diethyl O-p-nitrophenyl phosphorothioate
Diethyl O-p-nitrophenyl phosphorothioic acid
Diethyl p-nitrophenyl thionophosphate
Diethyl p-nitrophenyl thiophosphate
Diethyl para-nitrophenol thiophosphate
Diethyl-p-nitrophenyl monothiophosphate
Diethylparathion
Drexel parathion 8E
Durathion
Ecatox
Ethlon
Ethyl parathion
Ethyl parathion (O,O-diethyl-O-p-nitrophenylthiophosphate)
Etilon
Foliclal
Folidol
Folidol e e 605
Folidol e605
Folidol oil
Fosfermo
Fosferno
Fosferno 50
Fosfex
Fosfive
Fosova
Fostern
Fostox
Gearphos
Genithion
Kolphos
Kypthion
Lethalaire g-54
Lirothion
Murfos
Niran
Nitrostygmine
Niuif-100
Nourithion
O,O-Diethyl O-p-nitrophenyl phosphorothioate
O,O-Diethyl O-p-nitrophenyl phosphorothioic acid
O,O-Diethyl-O-(p-nitrophenyl)thionophosphate
Oleofos 20
Oleoparaphene
Oleoparathion
OMS 19
Orthophos
p-Nitrophenol O-ester with O,O-diethylphosphorothioate
p-Nitrophenol O-ester with O,O-diethylphosphorothioic acid
PAC
Pacol
Panthion
Paradust
Paramar
Paramar 50
Paraphos
Parathene
Parathion-E
Parawet
Parthion
Penncap e
Pestox plus
Pethion
Phoskil
Phosphemol
Phosphenol
Phosphorothioate
Phosphorothioic acid
Phosphorothioic acid O,O-diethyl-O-(4-nitrophenyl) ester
Phosphostigmine
Rhodiasol
Rhodiatox
Rhodiatrox
Selephos
Soprathion
Stabilized ethyl parathion
Stathion
Strathion
Sulfos
Super rodiatox
T-47
Thiomex
Thionspray No.84
Thiophos 3422
Tiofos
Vapophos
Viran
Vitrex
Chemical FormulaC10H14NO5PS
Average Molecular Mass291.261 g/mol
Monoisotopic Mass291.033 g/mol
CAS Registry Number56-38-2
IUPAC NameO,O-diethyl O-4-nitrophenyl phosphorothioate
Traditional Namebladen
SMILESCCOP(=S)(OCC)OC1=CC=C(C=C1)N(=O)=O
InChI IdentifierInChI=1S/C10H14NO5PS/c1-3-14-17(18,15-4-2)16-10-7-5-9(6-8-10)11(12)13/h5-8H,3-4H2,1-2H3
InChI KeyInChIKey=LCCNCVORNKJIRZ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenyl thiophosphates. These are organothiophosphorus compounds that contain a thiophosphoric acid O-esterified with a phenyl group.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassOrganic thiophosphoric acids and derivatives
Sub ClassThiophosphoric acid esters
Direct ParentPhenyl thiophosphates
Alternative Parents
Substituents
  • Phenyl thiophosphate
  • Nitrobenzene
  • Phenoxy compound
  • Nitroaromatic compound
  • Thiophosphate triester
  • Monocyclic benzene moiety
  • Benzenoid
  • C-nitro compound
  • Organic nitro compound
  • Organic oxoazanium
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateLiquid
AppearanceWhite crystals.
Experimental Properties
PropertyValue
Melting Point6.1°C
Boiling PointNot Available
Solubility0.011 mg/mL
LogP3.83
Predicted Properties
PropertyValueSource
Water Solubility0.013 g/LALOGPS
logP3.76ALOGPS
logP3.32ChemAxon
logS-4.4ALOGPS
pKa (Strongest Basic)-9.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area70.83 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity71.69 m³·mol⁻¹ChemAxon
Polarizability26.77 ųChemAxon
Number of Rings1ChemAxon
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, Positivesplash10-03fr-1390000000-256208006a2b1561db1bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-01p9-0090000000-fe8742077ddcdaa84280View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-0190000000-af44a385ea22b6326819View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000l-1940000000-218556da13b43e16e2bfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-01vo-2910000000-4a40f241595d8b5628d0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-01vo-4900000000-c58ec980fa6b4210133cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-01ox-6900000000-80ce5f0f59ebc4a62681View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-1090000000-e7daa1435a3c8202b8dcView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00lr-1090000000-0ee220c0c9ec67d726bbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004j-9720000000-be163305078ac89a7681View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0390000000-3cdf27289e65564f2028View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-0490000000-9b32c86de4c27c33c405View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000f-1940000000-6f5772e73d0e7958d6cbView in MoNA
MSMass Spectrum (Electron Ionization)splash10-0a74-8940000000-4bf55c77de23f747eb80View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureOral(17) ; inhalation (17) ; dermal (17).
Mechanism of ToxicityParathion is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
MetabolismMetabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.
Toxicity ValuesLD50: 2 mg/kg (Oral, Rat) (13) LD50: 6800 ug/kg (Dermal, Rat) (13) LD05: 3600 ug/kg (Intraperitoneal, Rat) (13) LD50: 6 mg/kg (Intramuscular, Rat) (13) LC50: 84.0 mg (Inhalation, Rat) (4)
Lethal Dose7143 mg/kg for an adult human. (14)
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (16)
Uses/SourcesParathion is an insecticide and acaricide that is generally applied by spraying, most often to cotton, rice, and fruit trees. (17)
Minimum Risk LevelNot Available
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
SymptomsParathion exposure can result in headaches, convulsions, poor vision, vomiting, abdominal pain, severe diarrhea, unconsciousness, tremor, dyspnea, and finally lung-edema as well as respiratory arrest. (17)
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB01355
PubChem Compound ID991
ChEMBL IDCHEMBL261919
ChemSpider ID13844817
KEGG IDC06604
UniProt IDNot Available
OMIM ID
ChEBI ID27928
BioCyc IDPARATHION
CTD IDD010278
Stitch IDParathion
PDB IDNot Available
ACToR ID1126
Wikipedia LinkParathion
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Mutch E, Daly AK, Leathart JB, Blain PG, Williams FM: Do multiple cytochrome P450 isoforms contribute to parathion metabolism in man? Arch Toxicol. 2003 Jun;77(6):313-20. Epub 2003 Mar 21. [12669189 ]
  2. Costa LG, Richter RJ, Li WF, Cole T, Guizzetti M, Furlong CE: Paraoxonase (PON 1) as a biomarker of susceptibility for organophosphate toxicity. Biomarkers. 2003 Jan-Feb;8(1):1-12. [12519632 ]
  3. Abel EL, Bammler TK, Eaton DL: Biotransformation of methyl parathion by glutathione S-transferases. Toxicol Sci. 2004 Jun;79(2):224-32. Epub 2004 Apr 21. [15103050 ]
  4. Wolf G: Serum retinol-binding protein: a link between obesity, insulin resistance, and type 2 diabetes. Nutr Rev. 2007 May;65(5):251-6. [17566551 ]
  5. Bohn G, Rucker G, Luckas KH: [Mass spectrometric and gaschromatographic detection of parathione in autopsy material after murder by poisoning]. Z Rechtsmed. 1971;68(1):45-52. [5547745 ]
  6. SALAMA S, EL-SHIHY A, IBRAHIM HH, KODSY A: THE ACTION OF PARATHIONE ON THE C.N.S. J Egypt Med Assoc. 1963;46:500-8. [14066548 ]
  7. Youssef SH, el-Sayed MG, Atef M: Influence of gentamicin and rifamycin on toxicity and biotransformation of methyl parathione in rats. Dtsch Tierarztl Wochenschr. 1987 Apr 8;94(4):203-5. [3297603 ]
  8. Innocenti A, Supuran CT: Paraoxon, 4-nitrophenyl phosphate and acetate are substrates of alpha- but not of beta-, gamma- and zeta-carbonic anhydrases. Bioorg Med Chem Lett. 2010 Nov 1;20(21):6208-12. doi: 10.1016/j.bmcl.2010.08.110. Epub 2010 Aug 26. [20833546 ]
  9. Kawahara K, Tanaka A, Yoon J, Yokota A: Reclassification of a parathione-degrading Flavobacterium sp. ATCC 27551 as Sphingobium fuliginis. J Gen Appl Microbiol. 2010 Jun;56(3):249-55. [20647682 ]
  10. Lotz W, Fasske E: [Pneumonitis with fatal pulmonary fibrosis (Hamman-Rich syndrome) due to parathion-(E-605-) poisoning]. Rofo. 1986 May;144(5):536-41. [3012677 ]
  11. SALAMA S, EL-SHISHY A, IBRAHIM HH: THE ACTION OF PARATHIONE ON THE CIRCULATORY & RESPIRATORY SYSTEMS. J Egypt Med Assoc. 1963;46:240-62. [14065272 ]
  12. Mueller RF, Hornung S, Furlong CE, Anderson J, Giblett ER, Motulsky AG: Plasma paraoxonase polymorphism: a new enzyme assay, population, family, biochemical, and linkage studies. Am J Hum Genet. 1983 May;35(3):393-408. [6305189 ]
  13. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  14. National Institute for Occupational Safety and Health (2002). RTECS: Registry of Toxic Effects of Chemical Substances.
  15. NIOSH: The National Institute for Occupational Safety and Health (1976). Criteria Document: Parathion.
  16. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  17. Wikipedia. Parathion. Last Updated 9 June 2009. [Link]
  18. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Toxicological profile for methyl parathion U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Serine hydrolase activity
Specific Function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular Weight:
67795.525 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Toxicological profile for methyl parathion U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Not Available
Specific Function:
Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
Gene Name:
FBF1
Uniprot ID:
Q8TES7
Molecular Weight:
125445.19 Da
References
  1. Silva D, Cortez CM, Cunha-Bastos J, Louro SR: Methyl parathion interaction with human and bovine serum albumin. Toxicol Lett. 2004 Feb 28;147(1):53-61. [14700528 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Bain LJ, LeBlanc GA: Interaction of structurally diverse pesticides with the human MDR1 gene product P-glycoprotein. Toxicol Appl Pharmacol. 1996 Nov;141(1):288-98. [8917702 ]
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
  1. Kojima H, Sata F, Takeuchi S, Sueyoshi T, Nagai T: Comparative study of human and mouse pregnane X receptor agonistic activity in 200 pesticides using in vitro reporter gene assays. Toxicology. 2011 Feb 27;280(3):77-87. doi: 10.1016/j.tox.2010.11.008. Epub 2010 Nov 27. [21115097 ]
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
AC500.19 uMNVS_ADME_hCYP2C19Novascreen
AC500.21 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:
Steroid hydroxylase activity
Specific Function:
This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible for the epoxidation of endogenous cardiac arachidonic acid pools.
Gene Name:
CYP2J2
Uniprot ID:
P51589
Molecular Weight:
57610.165 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.26 uMNVS_ADME_hCYP2J2Novascreen
AC500.34 uMNVS_ADME_hCYP2J2Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
AC500.96 uMNVS_ADME_hCYP2B6Novascreen
AC506.55 uMCLZD_CYP2B6_6CellzDirect
AC505.06 uMCLZD_CYP2B6_24CellzDirect
AC507.00 uMCLZD_CYP2B6_48CellzDirect
AC500.88 uMNVS_ADME_hCYP2B6Novascreen
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:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.16 uMNVS_ADME_hCYP3A5Novascreen
AC501.90 uMNVS_ADME_hCYP3A5Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP2C18
Uniprot ID:
P33260
Molecular Weight:
55710.075 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.80 uMNVS_ADME_hCYP2C18Novascreen
AC502.00 uMNVS_ADME_hCYP2C18Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.11 uMNVS_ADME_hCYP1A2Novascreen
AC506.26 uMCLZD_CYP1A2_6CellzDirect
AC502.40 uMNVS_ADME_hCYP1A2Novascreen
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:
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
AC502.27 uMNVS_NR_hARNovascreen
AC503.80 uMNVS_NR_hARNovascreen
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
AC502.45 uMNVS_ADME_hCYP2C9Novascreen
AC504.38 uMCLZD_CYP2C9_48CellzDirect
AC502.60 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:
Vitamin d 24-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular Weight:
58164.815 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.86 uMNVS_ADME_hCYP1A1Novascreen
AC507.50 uMCLZD_CYP1A1_6CellzDirect
AC507.10 uMNVS_ADME_hCYP1A1Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Transcription regulatory region dna binding
Specific Function:
Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
Gene Name:
AHR
Uniprot ID:
P35869
Molecular Weight:
96146.705 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.34 uMTox21_AhRTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Steroid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular Weight:
59590.91 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.72 uMCLZD_UGT1A1_24CellzDirect
AC509.60 uMCLZD_UGT1A1_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:
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
AC504.88 uMCLZD_CYP3A4_6CellzDirect
AC505.27 uMCLZD_CYP3A4_48CellzDirect
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
TypeValueAssay TypeAssay Source
AC507.48 uMCLZD_SULT2A1_6CellzDirect
AC505.39 uMCLZD_SULT2A1_24CellzDirect
AC505.15 uMCLZD_SULT2A1_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 ]