Metolachlor
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Basic Info
| Common Name | Metolachlor(F04086) |
| 2D Structure | |
| Description | Widely used selective herbicides worldwide in corn, soybean and other crop cultures. Elevated concentrations of these herbicides and their degradation products have been detected in surface and groundwater. (A252) Metolachlor is an organic compound that is widely used as a herbicide. It is a derivative of aniline and is a member of the chloroacetanilide herbicides. It is highly effective toward grasses but its application is also controversial (L913). |
| FRCD ID | F04086 |
| CAS Number | 51218-45-2 |
| PubChem CID | 4169 |
| Formula | C15H22ClNO2 |
| IUPAC Name | 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(1-methoxypropan-2-yl)acetamide |
| InChI Key | WVQBLGZPHOPPFO-UHFFFAOYSA-N |
| InChI | InChI=1S/C15H22ClNO2/c1-5-13-8-6-7-11(2)15(13)17(14(18)9-16)12(3)10-19-4/h6-8,12H,5,9-10H2,1-4H3 |
| Canonical SMILES | CCC1=CC=CC(=C1N(C(C)COC)C(=O)CCl)C |
| Isomeric SMILES | CCC1=CC=CC(=C1N(C(C)COC)C(=O)CCl)C |
| Synonyms |
Dual Magnum
metolachlor
51218-45-2
Dual
Yibingjiacaoan
Pennant
Codal
Dual Triple
Dual II
Ontrack 8E
|
| Classifies |
Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Benzene and substituted derivatives |
| Subclass | Anilides |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Anilides |
| Alternative Parents | |
| Molecular Framework | Aromatic homomonocyclic compounds |
| Substituents | Anilide - Toluene - Chloroacetamide - Tertiary carboxylic acid amide - Carboxamide group - Carboxylic acid derivative - Dialkyl ether - Ether - Alkyl chloride - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organochloride - Organohalogen compound - Organic oxide - Organopnictogen compound - Organic oxygen compound - Organic nitrogen compound - Carbonyl group - Alkyl halide - Aromatic homomonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as anilides. These are organic heterocyclic compounds derived from oxoacids RkE(=O)l(OH)m (l not 0) by replacing an OH group by the NHPh group or derivative formed by ring substitution. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 283.796 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 6 |
| Complexity | 285 |
| Monoisotopic Mass | 283.134 |
| Exact Mass | 283.134 |
| XLogP | 3.1 |
| Formal Charge | 0 |
| Heavy Atom Count | 19 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 1 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9869 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2+ | 0.6672 |
| P-glycoprotein Substrate | Non-substrate | 0.7740 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8141 |
| Non-inhibitor | 0.6114 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8036 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6953 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7786 |
| CYP450 2D6 Substrate | Non-substrate | 0.7100 |
| CYP450 3A4 Substrate | Substrate | 0.7008 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.5158 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8546 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8464 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.5706 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8309 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.5352 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9383 |
| Non-inhibitor | 0.7334 | |
| AMES Toxicity | AMES toxic | 0.5830 |
| Carcinogens | Carcinogens | 0.5584 |
| Fish Toxicity | Low FHMT | 0.5713 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.7462 |
| Honey Bee Toxicity | Low HBT | 0.8836 |
| Biodegradation | Not ready biodegradable | 0.9300 |
| Acute Oral Toxicity | III | 0.8066 |
| Carcinogenicity (Three-class) | Non-required | 0.6108 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.7926 | LogS |
| Caco-2 Permeability | 1.6793 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.1424 | LD50, mol/kg |
| Fish Toxicity | 0.8201 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.3630 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| S-metolachlor promotes oxidative stress in green microalga Parachlorella kessleri - A potential environmental and health risk for higher organisms. | Sci Total Environ | 2018 Oct 1 | 29751315 |
| The influence of natural dissolved organic matter on herbicide toxicity to marine microalgae is species-dependent. | Aquat Toxicol | 2018 May | 29529466 |
| Development of a new ecotoxicological assay using the testate amoeba Euglypha rotunda (Rhizaria; Euglyphida) and assessment of the impact of the herbicide S-metolachlor. | Chemosphere | 2018 Jun | 29525664 |
| A Retrospective Analysis of Agricultural Herbicides in Surface Water Reveals Risk Plausibility for Declines in Submerged Aquatic Vegetation. | Toxics | 2017 Sep 6 | 29051453 |
| Multiple Pesticides Detoxification Function of Maize (Zea mays) GST34. | J Agric Food Chem | 2017 Mar 8 | 28221787 |
| Mitigation of atrazine, S-metolachlor, and diazinon using common emergent aquaticvegetation. | J Environ Sci (China) | 2017 Jun | 28571845 |
| Variable Levels of Glutathione S-Transferases Are Responsible for theDifferential Tolerance to Metolachlor between Maize (Zea mays) Shoots and Roots. | J Agric Food Chem | 2017 Jan 11 | 27992212 |
| Aquatic concentrations of chemical analytes compared to ecotoxicity estimates. | Sci Total Environ | 2017 Feb 1 | 28040196 |
| Polymeric Nanoparticles as a Metolachlor Carrier: Water-Based Formulation forHydrophobic Pesticides and Absorption by Plants. | J Agric Food Chem | 2017 Aug 30 | 28783335 |
| Comparative toxic responses of male and female lizards (Eremias argus) exposed to (S)-metolachlor-contaminated soil. | Environ Pollut | 2017 Aug | 28494399 |
| Spatial and Temporal Variability in Pesticide Exposure Downstream of a HeavilyIrrigated Cropping Area: Application of Different Monitoring Techniques. | J Agric Food Chem | 2016 May 25 | 26755130 |
| Combined effects of pollutants and salinity on embryo-larval development of thePacific oyster, Crassostrea gigas. | Mar Environ Res | 2016 Feb | 26583531 |
| Metolachlor Sorption and Degradation in Soil Amended with Fresh and AgedBiochars. | J Agric Food Chem | 2016 Apr 27 | 27050383 |
| Effect of Organic Diet Intervention on Pesticide Exposures in Young ChildrenLiving in Low-Income Urban and Agricultural Communities. | Environ Health Perspect | 2015 Oct | 25861095 |
| Potential impacts of seasonal variation on atrazine and metolachlor persistencein andisol soil. | Environ Monit Assess | 2015 Dec | 26581606 |
| Community air monitoring for pesticides-part 2: multiresidue determination ofpesticides in air by gas chromatography, gas chromatography-mass spectrometry,and liquid chromatography-mass spectrometry. | Environ Monit Assess | 2014 Mar | 24370860 |
| Reduced herbicide leaching by in situ adsorption of herbicide-micelleformulations to soils. | J Agric Food Chem | 2014 Jan 8 | 24295204 |
| Rapid detection of atrazine and metolachlor in farm soils: gaschromatography-mass spectrometry-based analysis using the bubble-in-drop singledrop microextraction enrichment method. | J Agric Food Chem | 2014 Aug 6 | 25062345 |
| Synthesis and herbicidal potential of substituted aurones. | Pest Manag Sci | 2012 Nov | 22718431 |
| Organic micropollutants in rivers downstream of the megacity Beijing: sources andmass fluxes in a large-scale wastewater irrigation system. | Environ Sci Technol | 2012 Aug 21 | 22845779 |
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
References
- 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:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
- Gene Name:
- ESR2
- Uniprot ID:
- Q92731
- Molecular Weight:
- 59215.765 Da
- Mechanism of Action:
- Causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor.
References
- Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
- General Function:
- Receptor binding
- Specific Function:
- Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma.
- Gene Name:
- CHRNA10
- Uniprot ID:
- Q9GZZ6
- Molecular Weight:
- 49704.295 Da
- Mechanism of Action:
- Metolachlor acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It also binds to nAChRs in nervous systems.
References
- Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- General Function:
- Ligand-gated ion channel activity
- Specific Function:
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
- Gene Name:
- CHRNA3
- Uniprot ID:
- P32297
- Molecular Weight:
- 57479.54 Da
- Mechanism of Action:
- Metolachlor acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It also binds to nAChRs in nervous systems.
References
- Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- General Function:
- Ligand-gated ion channel activity
- Specific Function:
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions.
- Gene Name:
- CHRNA4
- Uniprot ID:
- P43681
- Molecular Weight:
- 69956.47 Da
- Mechanism of Action:
- Metolachlor acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It also binds to nAChRs in nervous systems.
References
- Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- General Function:
- Ligand-gated ion channel activity
- Specific Function:
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
- Gene Name:
- CHRNA5
- Uniprot ID:
- P30532
- Molecular Weight:
- 53053.965 Da
- Mechanism of Action:
- Metolachlor acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It also binds to nAChRs in nervous systems.
References
- Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- General Function:
- Toxic substance binding
- Specific Function:
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin.
- Gene Name:
- CHRNA7
- Uniprot ID:
- P36544
- Molecular Weight:
- 56448.925 Da
- Mechanism of Action:
- Metolachlor acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It also binds to nAChRs in nervous systems.
References
- Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- General Function:
- Ligand-gated ion channel activity
- Specific Function:
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodiun ions.
- Gene Name:
- CHRNB2
- Uniprot ID:
- P17787
- Molecular Weight:
- 57018.575 Da
- Mechanism of Action:
- Metolachlor acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It also binds to nAChRs in nervous systems.
References
- Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- General Function:
- Drug binding
- Specific Function:
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
- Gene Name:
- CHRNB3
- Uniprot ID:
- Q05901
- Molecular Weight:
- 52728.215 Da
- Mechanism of Action:
- Metolachlor acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It also binds to nAChRs in nervous systems.
References
- Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- General Function:
- Ligand-gated ion channel activity
- Specific Function:
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
- Gene Name:
- CHRNB4
- Uniprot ID:
- P30926
- Molecular Weight:
- 56378.985 Da
- Mechanism of Action:
- Metolachlor acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It also binds to nAChRs in nervous systems.
References
- Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- 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
- Mechanism of Action:
- Metolachlor inhibits MRD1.
References
- Oosterhuis B, Vukman K, Vagi E, Glavinas H, Jablonkai I, Krajcsi P: Specific interactions of chloroacetanilide herbicides with human ABC transporter proteins. Toxicology. 2008 Jun 3;248(1):45-51. doi: 10.1016/j.tox.2008.03.003. Epub 2008 Mar 14. [18433974 ]
- General Function:
- Temperature-gated cation channel activity
- Specific Function:
- Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
- Gene Name:
- TRPA1
- Uniprot ID:
- O75762
- Molecular Weight:
- 127499.88 Da
References
- Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
- Gene Name:
- AR
- Uniprot ID:
- P10275
- Molecular Weight:
- 98987.9 Da
References
- 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:
- Transferase activity
- Specific Function:
- Synthesizes the second messagers cyclic ADP-ribose and nicotinate-adenine dinucleotide phosphate, the former a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system.
- Gene Name:
- CD38
- Uniprot ID:
- P28907
- Molecular Weight:
- 34328.145 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- 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
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
- Gene Name:
- CYP2B6
- Uniprot ID:
- P20813
- Molecular Weight:
- 56277.81 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
- Gene Name:
- CYP2C19
- Uniprot ID:
- P33261
- Molecular Weight:
- 55930.545 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- 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
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Vitamin 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
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Cholesterol binding
- Specific Function:
- Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
- Gene Name:
- TSPO
- Uniprot ID:
- P30536
- Molecular Weight:
- 18827.81 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Steroid 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
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Acetylcholine-activated cation-selective channel activity
- Specific Function:
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
- Gene Name:
- CHRNA6
- Uniprot ID:
- Q15825
- Molecular Weight:
- 56897.745 Da
- Mechanism of Action:
- Metolachlor acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It also binds to nAChRs in nervous systems.
References
- Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
- Mechanism of Action:
- Causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor.
References
- Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
- General Function:
- Calcium channel activity
- Specific Function:
- Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding induces a conformation change that leads to the opening of an ion-conducting channel across the plasma membrane (PubMed:11752216, PubMed:25282151). The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane (PubMed:11752216, PubMed:25282151). In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma. May also regulate keratinocyte adhesion (PubMed:11021840).
- Gene Name:
- CHRNA9
- Uniprot ID:
- Q9UGM1
- Molecular Weight:
- 54806.63 Da
- Mechanism of Action:
- Metolachlor acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It also binds to nAChRs in nervous systems.
References
- Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- General Function:
- Vitamin d3 25-hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
- Gene Name:
- CYP3A4
- Uniprot ID:
- P08684
- Molecular Weight:
- 57342.67 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
- Gene Name:
- OPRM1
- Uniprot ID:
- P35372
- Molecular Weight:
- 44778.855 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]