Basic Info

Common NameSimazine(F05136)
2D Structure
Description

Simazine is a herbicide of the triazine class. The compound is used to control broad-leaved weeds and annual grasses.

FRCD IDF05136
CAS Number122-34-9
PubChem CID5216
FormulaC7H12ClN5
IUPAC Name

6-chloro-2-N,4-N-diethyl-1,3,5-triazine-2,4-diamine

InChI Key

ODCWYMIRDDJXKW-UHFFFAOYSA-N

InChI

InChI=1S/C7H12ClN5/c1-3-9-6-11-5(8)12-7(13-6)10-4-2/h3-4H2,1-2H3,(H2,9,10,11,12,13)

Canonical SMILES

CCNC1=NC(=NC(=N1)Cl)NCC

Isomeric SMILES

CCNC1=NC(=NC(=N1)Cl)NCC

Synonyms
        
            simazine
        
            122-34-9
        
            Gesatop
        
            Princep
        
            Simanex
        
            Aquazine
        
            Batazina
        
            Herbazin
        
            Symazine
        
            Tafazine
        
Classifies
                

                  
                    Pesticide
                  

                
        
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassOrganoheterocyclic compounds
ClassTriazines
Subclass1,3,5-triazines
Intermediate Tree NodesHalo-S-triazines
Direct ParentChloro-s-triazines
Alternative Parents
Molecular FrameworkAromatic heteromonocyclic compounds
SubstituentsChloro-s-triazine - Aryl halide - Aryl chloride - Heteroaromatic compound - Azacycle - Organic nitrogen compound - Organopnictogen compound - Hydrocarbon derivative - Organonitrogen compound - Organochloride - Organohalogen compound - Aromatic heteromonocyclic compound
DescriptionThis compound belongs to the class of organic compounds known as chloro-s-triazines. These are aromatic compounds containing a 1,3,5-triazine ring that is substituted at the 2-position with a chlorine atom.

Properties

Property NameProperty Value
Molecular Weight201.658
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count5
Rotatable Bond Count4
Complexity131
Monoisotopic Mass201.078
Exact Mass201.078
XLogP2.2
Formal Charge0
Heavy Atom Count13
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.8594
Human Intestinal AbsorptionHIA+0.9839
Caco-2 PermeabilityCaco2+0.5393
P-glycoprotein SubstrateNon-substrate0.6043
P-glycoprotein InhibitorNon-inhibitor0.9263
Non-inhibitor0.8606
Renal Organic Cation TransporterNon-inhibitor0.7265
Distribution
Subcellular localizationLysosome0.5659
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8832
CYP450 2D6 SubstrateNon-substrate0.8120
CYP450 3A4 SubstrateNon-substrate0.7022
CYP450 1A2 InhibitorInhibitor0.8235
CYP450 2C9 InhibitorNon-inhibitor0.9307
CYP450 2D6 InhibitorNon-inhibitor0.7787
CYP450 2C19 InhibitorNon-inhibitor0.5233
CYP450 3A4 InhibitorNon-inhibitor0.9375
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.7674
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.7720
Non-inhibitor0.8433
AMES ToxicityNon AMES toxic0.9132
CarcinogensNon-carcinogens0.8010
Fish ToxicityLow FHMT0.8264
Tetrahymena Pyriformis ToxicityHigh TPT0.9899
Honey Bee ToxicityLow HBT0.8340
BiodegradationNot ready biodegradable0.9959
Acute Oral ToxicityIII0.8212
Carcinogenicity (Three-class)Warning0.4471

Model Value Unit
Absorption
Aqueous solubility-4.2631LogS
Caco-2 Permeability1.3154LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.3366LD50, mol/kg
Fish Toxicity2.1469pLC50, mg/L
Tetrahymena Pyriformis Toxicity0.3257pIGC50, ug/L

MRLs

FoodProduct CodeCountryMRLsApplication DateNotes
PearJapan0.2ppm
Others (2)0212990European Union0.01*21/10/2011
Cassava roots/manioc (Blue taros/blue tannias, Canna, Chayotes/christophines roots, Dasheen taros, Eddoe taros, Konjac roots, Tannias/arrowleaf elephant ears/tajer,)0212010European Union0.01*21/10/2011
Sweet potatoes0212020European Union0.01*21/10/2011
Yams (Amazonian yam beans/potato beans, American groundnuts tubers, Andean yam beans, Mexican yam beans,)0212030European Union0.01*21/10/2011
Citrus fruits0110000European Union0.01*21/10/2011
Grapefruits (Natsudaidais, Shaddocks/pomelos, Sweeties/oroblancos, Tangelolos, Tangelos (except minneolas)/Ugli®, Other hybrids of Citrus paradisi, not elsewhere mentioned,)0110010European Union0.01*21/10/2011
Oranges (Bergamots, Bitter oranges/sour oranges, Blood oranges, Cara caras, Chinottos, Trifoliate oranges, Other hybrids of Citrus sinensis, not elsewhere mentioned,)0110020European Union0.01*21/10/2011
Lemons (Buddha's hands/Buddha's fingers, Citrons,)0110030European Union0.01*21/10/2011
Limes (Indian sweet limes/Palestine sweet limes, Kaffir limes, Sweet limes/mosambis, Tahiti limes, Limequats,)0110040European Union0.01*21/10/2011
Mandarins (Calamondins, Clementines, Cleopatra mandarins, Minneolas, Satsumas/clausellinas, Tangerines/dancy mandarins, Tangors, Other hybrids of Citrus reticulata, not elsewhere mentioned,)0110050European Union0.01*21/10/2011
Others (2)0110990European Union0.01*21/10/2011
Tree nuts0120000European Union0.02*21/10/2011
Almonds (Apricot kernels, Bitter almonds, Canarium nuts/galip nuts, Pili nuts, Okari nuts,)0120010European Union0.02*21/10/2011
Brazil nuts0120020European Union0.02*21/10/2011
Cashew nuts0120030European Union0.02*21/10/2011
Chestnuts0120040European Union0.02*21/10/2011
Coconuts (Areca nuts/betel nuts,)0120050European Union0.02*21/10/2011
Hazelnuts/cobnuts (Acorns, Filberts,)0120060European Union0.02*21/10/2011
Macadamias0120070European Union0.02*21/10/2011

References

TitleJournalDatePubmed ID
Occurrence, impact variables and potential risk of PPCPs and pesticides in adrinking water reservoir and related drinking water treatment plants in theYangtze Estuary.Environ Sci Process Impacts2018 Jul 1829900462
Fast pesticide detection inside microfluidic device with integrated optical pH, oxygen sensors and algal fluorescence.Biosens Bioelectron2017 Feb 1527523821
Novel hydrolytic de-methylthiolation of the s-triazine herbicide prometryn byLeucobacter sp. JW-1.Sci Total Environ2017 Feb 127866738
Self-assembled magnetic nanoparticle supported zeolitic imidazolate framework-8: An efficient adsorbent for the enrichment of triazine herbicides from fruit,vegetables, and water.J Sep Sci2017 Feb27987275
Influence of Three Citrus Herbicides on Potential Production of Sorghum bicolor 'Topper 76-6' as a Bioenergy Crop.Bull Environ Contam Toxicol2016 Nov27686087
How benthic diatoms within natural communities respond to eight common herbicides with different modes of action.Sci Total Environ2016 Jul 127037885
A new amino acid substitution (Ala-205-Phe) in acetolactate synthase (ALS)confers broad spectrum resistance to ALS-inhibiting herbicides.Planta2016 Jan26353912
Aquatic risk assessment of priority and other river basin specific pesticides in surface waters of Mediterranean river basins.Chemosphere2015 Sep26002046
Sorption interactions of organic compounds with soils affected by agriculturalolive mill wastewater.Chemosphere2015 Nov26183941
Multiresidue method for the quantitation of 20 pesticides in aquatic products.Anal Bioanal Chem2015 Dec26466578
Emerging contaminants (pharmaceuticals, personal care products, a food additiveand pesticides) in waters of Sydney estuary, Australia.Mar Pollut Bull2015 Aug 1526130525
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 Assess2014 Mar24370860
New competitive dendrimer-based and highly selective immunosensor fordetermination of atrazine in environmental, feed and food samples: the importanceof antibody selectivity for discrimination among related triazinic metabolites.Anal Chim Acta2014 Jan 224331056
Simultaneous voltammetric determination of four triazine herbicides in watersamples with the aid of chemometrics.J Environ Sci Health B201425065823
Online sequential-injection chromatography with stepwise gradient elution: a toolfor studying the simultaneous adsorption of herbicides on soil and soilcomponents.J Agric Food Chem2013 Aug 2123875679
Triazine residues in raw milk and infant formulas from Spanish northwest, by adiphasic dialysis extraction.Food Chem Toxicol2012 Mar22137903
Dispersive liquid-liquid microextraction method based on solidification offloating organic droplet for the determination of triazine herbicides in waterand sugarcane samples.Food Chem2012 Jul 1525683433
A pilot survey of 39 Victorian WWTP effluents using a high speed luminescent umu test in conjunction with a novel GC-MS-database technique for automaticidentification of micropollutants.Water Sci Technol201222766865
Study of the surface ionization detector for gas chromatography.J Chromatogr A2011 Sep 2321839459
Absorption of current use pesticides by snapping turtle (Chelydra serpentina)eggs in treated soil.Chemosphere2011 Oct21862099

Targets

General Function:
Urokinase plasminogen activator receptor activity
Specific Function:
Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.
Gene Name:
PLAUR
Uniprot ID:
Q03405
Molecular Weight:
36977.62 Da
References
  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
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:
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
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Cytokine activity
Specific Function:
Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.
Gene Name:
IL1A
Uniprot ID:
P01583
Molecular Weight:
30606.29 Da
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Receptor binding
Specific Function:
Chemotactic for monocytes and T-lymphocytes. Binds to CXCR3.
Gene Name:
CXCL10
Uniprot ID:
P02778
Molecular Weight:
10880.915 Da
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:
Tumor necrosis factor receptor binding
Specific Function:
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:22517918).The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
Gene Name:
TNF
Uniprot ID:
P01375
Molecular Weight:
25644.15 Da
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Primary amine oxidase activity
Specific Function:
Important in cell-cell recognition. Appears to function in leukocyte-endothelial cell adhesion. Interacts with integrin alpha-4/beta-1 (ITGA4/ITGB1) on leukocytes, and mediates both adhesion and signal transduction. The VCAM1/ITGA4/ITGB1 interaction may play a pathophysiologic role both in immune responses and in leukocyte emigration to sites of inflammation.
Gene Name:
VCAM1
Uniprot ID:
P19320
Molecular Weight:
81275.43 Da
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
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:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4A
Uniprot ID:
P27815
Molecular Weight:
98142.155 Da
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear 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
References
  1. Tran DQ, Kow KY, McLachlan JA, Arnold SF: The inhibition of estrogen receptor-mediated responses by chloro-S-triazine-derived compounds is dependent on estradiol concentration in yeast. Biochem Biophys Res Commun. 1996 Oct 3;227(1):140-6. [8858116 ]
General Function:
Ubiquitin protein ligase binding
Specific Function:
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.Isoform 2 may act as an antagonist of EGF action.
Gene Name:
EGFR
Uniprot ID:
P00533
Molecular Weight:
134276.185 Da
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
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 ]