Tetramethrin (T3D1028)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (28)XML
Targets (28)
Record Information
Version2.0
Creation Date2009-06-18 17:03:35 UTC
Update Date2014-12-24 20:23:04 UTC
Accession NumberT3D1028
Identification
Common NameTetramethrin
ClassSmall Molecule
DescriptionTetramethrin is a potent synthetic insecticide in the pyrethroid (type 1) family. A pyrethroid is a synthetic chemical compound similar to the natural chemical pyrethrins produced by the flowers of pyrethrums (Chrysanthemum cinerariaefolium and C. coccineum). Pyrethroids are common in commercial products such as household insecticides and insect repellents. In the concentrations used in such products, they are generally harmless to human beings but can harm sensitive individuals. They are usually broken apart by sunlight and the atmosphere in one or two days, and do not significantly affect groundwater quality except for being toxic to fish. (6)
Compound Type
  • Amide
  • Amine
  • Ester
  • Ether
  • Household Toxin
  • Organic Compound
  • Pesticide
  • Pyrethroid
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(1-Cyclohexene-1,2-dicarboximido)methyl chrysanthemate
(1-Cyclohexene-1,2-dicarboximido)methyl chrysanthemumate
Cyclohexene-1-dicarboximidomethylchrysanthemate
Etramethrin isomer
Killgerm PY-kill w
N-(Chrysanthemoxymethyl)-1-cyclohexene-1,2-dicarboximide
Neo-pynamin
Neopinamin
Neopinamine
Neopynamin
Phthalthrin
PY-kill
Tetramethrin isomer
Chemical FormulaC19H25NO4
Average Molecular Mass331.406 g/mol
Monoisotopic Mass331.178 g/mol
CAS Registry Number7696-12-0
IUPAC Name(1,3-dioxo-2,3,4,5,6,7-hexahydro-1H-isoindol-2-yl)methyl 2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropane-1-carboxylate
Traditional Nametetramethrin
SMILESCC(C)=CC1C(C(=O)OCN2C(=O)C3=C(CCCC3)C2=O)C1(C)C
InChI IdentifierInChI=1S/C19H25NO4/c1-11(2)9-14-15(19(14,3)4)18(23)24-10-20-16(21)12-7-5-6-8-13(12)17(20)22/h9,14-15H,5-8,10H2,1-4H3
InChI KeyInChIKey=CXBMCYHAMVGWJQ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as isoindolones. These are aromatic polycyclic compounds that an isoindole bearing a ketone.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIsoindoles and derivatives
Sub ClassIsoindolines
Direct ParentIsoindolones
Alternative Parents
Substituents
  • Bicyclic monoterpenoid
  • Isoindolone
  • Monoterpenoid
  • Isoindole
  • Maleimide
  • Cyclopropanecarboxylic acid or derivatives
  • Carboxylic acid imide, n-substituted
  • Pyrroline
  • Carboxylic acid imide
  • Dicarboximide
  • Carboxylic acid ester
  • Lactam
  • Azacycle
  • Carboxylic acid derivative
  • Monocarboxylic acid or derivatives
  • Organooxygen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Organic nitrogen compound
  • Organonitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic 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
AppearanceThe racemic isomer is a colourless crystalline solid. The (1R)-isomer is a yellow or brown viscous liquid (8).
Experimental Properties
PropertyValue
Melting Point69°C
Boiling PointNot Available
Solubility0.00183 mg/mL at 25°C [TOMLIN,C (1997)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.075 g/LALOGPS
logP2.84ALOGPS
logP3.09ChemAxon
logS-3.6ALOGPS
pKa (Strongest Basic)-4.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area63.68 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity90.19 m³·mol⁻¹ChemAxon
Polarizability36.16 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2020-08-04View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0w30-0914000000-8d0f8879961828dc6abf2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0ik9-1900000000-962d8c4288f0e1b2d7b82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0zgi-9600000000-3a0666ffcfaf453348bf2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0fai-0904000000-2534905791b09dd444872016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-1901000000-81333aa37d4f7eae1da02016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0pk9-2900000000-a348ae4a06d6c20ce6372016-08-03View Spectrum
Toxicity Profile
Route of ExposureInhalation (7) ; oral (7) ; dermal (7) ; eye contact (7).
Mechanism of ToxicityBoth type I and type II pyrethroids exert their effect by prolonging the open phase of the sodium channel gates when a nerve cell is excited. They appear to bind to the membrane lipid phase in the immediate vicinity of the sodium channel, thus modifying the channel kinetics. This blocks the closing of the sodium gates in the nerves, and thus prolongs the return of the membrane potential to its resting state. The repetitive (sensory, motor) neuronal discharge and a prolonged negative afterpotential produces effects quite similar to those produced by DDT, leading to hyperactivity of the nervous system which can result in paralysis and/or death. Other mechanisms of action of pyrethroids include antagonism of gamma-aminobutyric acid (GABA)-mediated inhibition, modulation of nicotinic cholinergic transmission, enhancement of noradrenaline release, and actions on calcium ions. They also inhibit calium channels and Ca2+, Mg2+-ATPase. (3, 4, 7)
MetabolismThe reactions occuring during metabolism of tetramethrin are: ester cleavage; loss of the hydroxymethyl group from the alcohol moiety; reduction of the 1-2 bond of the alcohol moiety; oxidation at the isobutenyl methyl moiety of the acid and at the 2-, 3-, and 4-positions of the alcohol moiety; conjugation of the resultant acids and alcohols with glucuronic acid; and cis/trans isomerization. The metabolites are excreted in the urine and faeces in more or less equal amounts. (8)
Toxicity ValuesLD50: 5000 mg/kg (Oral, Rat) (8) LD50 (racemate isomer): 2000 mg/kg (Oral, Mouse) (8) LD50 (1R-isomer): 1060 mg/kg (Oral, Mouse) (8)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesPyrethroids are used as insecticides. (7)
Minimum Risk LevelNot Available
Health EffectsPyrethroid effects typically include rapid onset of aggressive behavior and increased sensitivity to external stimuli, followed by fine tremor, prostration with coarse whole body tremor, elevated body temperature, coma, and death. Paresthesia, severe corneal damage, hypotension and tachycardia, associated with anaphylaxis, can also occur following pyrethriod poisoning. (7)
SymptomsFollowing oral exposure, severe fine tremor, marked reflex hyperexcitability, sympathetic activation can occur. Nausea, vomiting and abdominal pain commonly occur and develop following ingestion. Sudden bronchospasm, swelling of oral and laryngeal mucous membranes, and anaphylactoid reactions have been reported after inhalation. Hypersensitivity reactions characterized by pneumonitis, cough, dyspnea, wheezing, chest pain, irritability to sound and touch, and bronchospasm may occur too . Dermatitis is the main effect of a dermal exposure to tetramethrin. (5)
TreatmentFollowing oral exposure, the treatment is symptomatic and supportive and includes monitoring for the development of hypersensitivity reactions with respiratory distress. Provide adequate airway management when needed. Gastric decontamination is usually not required unless the pyrethrin product is combined with a hydrocarbon. Following inhalation exposure, move patient to fresh air. monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. In case of eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist, the patient should be seen in a health care facility. If the contamination occurs through dermal exposure, Remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists. Vitamin E topical application is highly effective in relieving parenthesis. (9)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID83975
ChEMBL IDCHEMBL1788386
ChemSpider ID75773
KEGG IDC18373
UniProt IDNot Available
OMIM ID
ChEBI ID39397
BioCyc IDNot Available
CTD IDC009424
Stitch IDTetramethrin
PDB IDNot Available
ACToR ID7851
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D1028.pdf
General References
  1. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [18948380 ]
  2. Leng G, Lewalter J, Rohrig B, Idel H: The influence of individual susceptibility in pyrethroid exposure. Toxicol Lett. 1999 Jun 30;107(1-3):123-30. [10414789 ]
  3. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
  4. Hayes WJ Jr. and Laws ER Jr. (eds) (1991). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc.
  5. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  6. Wikipedia. Pyrethroid. Last Updated 8 June 2009. [Link]
  7. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  8. International Programme on Chemical Safety (IPCS) INCHEM (1989). Health and Safety Guide forTetramethrin. [Link]
  9. Wikipedia. Blister agent. Last Updated 24 May 2009. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Sodium channel protein type 1 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN1A
Uniprot ID:
P35498
Molecular Weight:
228969.49 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
2. Sodium channel protein type 10 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.
Gene Name:
SCN10A
Uniprot ID:
Q9Y5Y9
Molecular Weight:
220623.605 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
3. Sodium channel protein type 11 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant sodium channel isoform. Also involved, with the contribution of the receptor tyrosine kinase NTRK2, in rapid BDNF-evoked neuronal depolarization.
Gene Name:
SCN11A
Uniprot ID:
Q9UI33
Molecular Weight:
204919.66 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
4. Sodium channel protein type 2 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN2A
Uniprot ID:
Q99250
Molecular Weight:
227972.64 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
5. Sodium channel protein type 3 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN3A
Uniprot ID:
Q9NY46
Molecular Weight:
226291.905 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
6. Sodium channel protein type 4 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle.
Gene Name:
SCN4A
Uniprot ID:
P35499
Molecular Weight:
208059.175 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
7. Sodium channel protein type 5 subunit alpha
General Function:
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
8. Sodium channel protein type 7 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN7A
Uniprot ID:
Q01118
Molecular Weight:
193491.605 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
9. Sodium channel protein type 8 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation.
Gene Name:
SCN8A
Uniprot ID:
Q9UQD0
Molecular Weight:
225278.005 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
10. Sodium channel protein type 9 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain (By similarity).
Gene Name:
SCN9A
Uniprot ID:
Q15858
Molecular Weight:
226370.175 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
11. Sodium channel subunit beta-1
General Function:
Voltage-gated sodium channel activity involved in purkinje myocyte action potential
Specific Function:
Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-1 can modulate multiple alpha subunit isoforms from brain, skeletal muscle, and heart. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons.Isoform 2: Cell adhesion molecule that plays a critical role in neuronal migration and pathfinding during brain development. Stimulates neurite outgrowth.
Gene Name:
SCN1B
Uniprot ID:
Q07699
Molecular Weight:
24706.955 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
12. Sodium channel subunit beta-2
General Function:
Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:
Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-2 causes an increase in the plasma membrane surface area and in its folding into microvilli. Interacts with TNR may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier (By similarity).
Gene Name:
SCN2B
Uniprot ID:
O60939
Molecular Weight:
24325.69 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
13. Sodium channel subunit beta-3
General Function:
Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:
Modulates channel gating kinetics. Causes unique persistent sodium currents. Inactivates the sodium channel opening more slowly than the subunit beta-1. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons (By similarity).
Gene Name:
SCN3B
Uniprot ID:
Q9NY72
Molecular Weight:
24702.08 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
14. Sodium channel subunit beta-4
General Function:
Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:
Modulates channel gating kinetics. Causes negative shifts in the voltage dependence of activation of certain alpha sodium channels, but does not affect the voltage dependence of inactivation. Modulates the suceptibility of the sodium channel to inhibition by toxic peptides from spider, scorpion, wasp and sea anemone venom.
Gene Name:
SCN4B
Uniprot ID:
Q8IWT1
Molecular Weight:
24968.755 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
15. Calcium-transporting ATPase type 2C member 1
General Function:
Signal transducer activity
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.
Gene Name:
ATP2C1
Uniprot ID:
P98194
Molecular Weight:
100576.42 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
Target Details
16. Calcium-transporting ATPase type 2C member 2
General Function:
Metal ion binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium.
Gene Name:
ATP2C2
Uniprot ID:
O75185
Molecular Weight:
103186.475 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
Target Details
17. Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
General Function:
Protein homodimerization activity
Specific Function:
Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Gene Name:
ATP2A1
Uniprot ID:
O14983
Molecular Weight:
110251.36 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
Target Details
18. Sarcoplasmic/endoplasmic reticulum calcium ATPase 2
General Function:
S100 protein binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the contraction/relaxation cycle.
Gene Name:
ATP2A2
Uniprot ID:
P16615
Molecular Weight:
114755.765 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
Target Details
19. Sarcoplasmic/endoplasmic reticulum calcium ATPase 3
General Function:
Metal ion binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Gene Name:
ATP2A3
Uniprot ID:
Q93084
Molecular Weight:
113976.23 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
Target Details
20. Matrix metalloproteinase-9
General Function:
Zinc ion binding
Specific Function:
May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.
Gene Name:
MMP9
Uniprot ID:
P14780
Molecular Weight:
78457.51 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_KF3CT_MMP9_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 ]
Target Details
21. Cytochrome P450 3A4
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
AC503.63 uMCLZD_CYP3A4_6CellzDirect
AC507.09 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 ]
Target Details
22. C-C motif chemokine 2
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
AC504.44 uMBSK_LPS_MCP1_downBioSeek
AC504.44 uMBSK_3C_MCP1_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 ]
Target Details
23. E-selectin
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_SAg_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 ]
Target Details
24. Prostaglandin E2 receptor EP2 subtype
General Function:
Prostaglandin e receptor activity
Specific Function:
Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle.
Gene Name:
PTGER2
Uniprot ID:
P43116
Molecular Weight:
39759.945 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_LPS_PGE2_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 ]
Target Details
25. Cytochrome P450 2B6
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
AC504.64 uMCLZD_CYP2B6_6CellzDirect
AC505.03 uMCLZD_CYP2B6_24CellzDirect
AC509.30 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 ]
Target Details
26. Hepatocyte nuclear factor 4-alpha
General Function:
Zinc ion binding
Specific Function:
Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.
Gene Name:
HNF4A
Uniprot ID:
P41235
Molecular Weight:
52784.205 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.83 uMATG_HNF4a_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
27. Nuclear receptor subfamily 1 group I member 2
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
AC504.96 uMNVS_NR_hPXRNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
28. Cytochrome P450 2C19
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
AC506.82 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 ]