Clothianidin (T3D3815)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (8)XML
Targets (8)
Record Information
Version2.0
Creation Date2013-04-25 07:56:50 UTC
Update Date2014-12-24 20:26:32 UTC
Accession NumberT3D3815
Identification
Common NameClothianidin
ClassSmall Molecule
DescriptionClothianidin is a neonicotinoid insecticide, which is a class of neuro-active insecticides modeled after nicotine. Nicotine was identified and used as an insecticide and rat poison as early as the 1600’s. Its effectiveness as an insecticide spurred a search for insecticidal compounds that have selectively less effect on mammals, which led to the discovery of neonicotinoids. Neonicotinoids, like nicotine, bind to nicotinic acetylcholine receptors of a cell. In mammals, nicotinic acetylcholine receptors are located in cells of both the central and peripheral nervous systems. In insects these receptors are limited to the CNS. While low to moderate activation of these receptors causes nervous stimulation, high levels overstimulate and block the receptors causing paralysis and death. Nicotinic acetylcholine receptors are activated by the neurotransmitter acetylcholine. Acetylcholine is broken down by acetylcholinesterase to terminate signals from these receptors. However, acetylcholinesterase cannot break down neonicotinoids and the binding is irreversible. Because most neonicotinoids bind much more strongly to insect neuron receptors than to mammal neuron receptors, these insecticides are selectively more toxic to insects than mammals. The low mammalian toxicity of neonicotinoids can be explained in large part by their lack of a charged nitrogen atom at physiological pH. The uncharged molecule can penetrate the insect blood–brain barrier, while the mammalian blood–brain barrier filters it. However, Some neonicotinoid breakdown products are toxic to humans, especially if they have become charged. Because of their low toxicity and other favorable features, neonicotinoids are among the most widely used insecticides in the world. Most neonicotinoids are water-soluble and break down slowly in the environment, so they can be taken up by the plant and provide protection from insects as the plant grows. Neonicotinoids are currently used on corn, canola, cotton, sorghum, sugar beets and soybeans. They are also used on the vast majority of fruit and vegetable crops, including apples, cherries, peaches, oranges, berries, leafy greens, tomatoes, and potatoes. The use of neonicotinoids has been linked in a range of studies to adverse ecological effects, including honey-bee colony collapse disorder (CCD) and loss of birds due to a reduction in insect populations. This has led to moratoriums and bans on their use in Europe.
Compound Type
  • Amine
  • Insecticide
  • Organic Compound
  • Organochloride
  • Pesticide
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
(e)-N-(2-chloro-5-Thiazolyl)methyl-n'-methyl-n''-nitroguanidine
Chemical FormulaC6H8ClN5O2S
Average Molecular Mass249.678 g/mol
Monoisotopic Mass249.009 g/mol
CAS Registry Number210880-92-5
IUPAC Name(E)-N'-[(2-chloro-1,3-thiazol-5-yl)methyl]-N-methyl-N''-nitroguanidine
Traditional Namecelero
SMILESCN\C(NCC1=CN=C(Cl)S1)=N/[N+]([O-])=O
InChI IdentifierInChI=1S/C6H8ClN5O2S/c1-8-6(11-12(13)14)10-3-4-2-9-5(7)15-4/h2H,3H2,1H3,(H2,8,10,11)
InChI KeyInChIKey=PGOOBECODWQEAB-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 2,5-disubstituted thiazoles. 2,5-disubstituted thiazoles are compounds containing a thiazole ring substituted at positions 2 and 5 only.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzoles
Sub ClassThiazoles
Direct Parent2,5-disubstituted thiazoles
Alternative Parents
Substituents
  • 2,5-disubstituted 1,3-thiazole
  • Nitroguanidine
  • Aryl chloride
  • Aryl halide
  • Nitramine
  • Heteroaromatic compound
  • Guanidine
  • Organic nitro compound
  • Carboximidamide
  • Allyl-type 1,3-dipolar organic compound
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Azacycle
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Imine
  • Organic zwitterion
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.11 g/LALOGPS
logP0.62ALOGPS
logP0.54ChemAxon
logS-3.4ALOGPS
pKa (Strongest Basic)0.41ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area92.45 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity55.53 m³·mol⁻¹ChemAxon
Polarizability22.17 ųChemAxon
Number of Rings1ChemAxon
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
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT 17V, positivesplash10-014i-0910000000-6385f1a3a7f91ed7e9822020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT 7V, positivesplash10-0gc0-0950000000-d29e3319f44939e2ffe72020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT 14V, positivesplash10-0159-0900000000-653b260bb023add99e312020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT 22V, positivesplash10-00lr-0900000000-b5f88b04d76924d173782020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT 29V, positivesplash10-01q9-0900000000-ed2f06c069aed87e9f9e2020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT 37V, positivesplash10-03e9-0900000000-f9169babd128a490c6892020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT 44V, positivesplash10-03e9-2900000000-84040d7ff64bca37fde82020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT 17V, positivesplash10-0159-0900000000-97745f6dc45dd15817652020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ 10V, positivesplash10-014i-0920000000-fec4e86ce184bd2526652020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ 20V, positivesplash10-02u0-0900000000-c422082c73e9f46c27132020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ 30V, positivesplash10-03e9-0900000000-d266e4d6dacfa337ada02020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ 40V, positivesplash10-03di-0900000000-019d795fba7ac99240cf2020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 10V, positivesplash10-0gb9-0940000000-d3f42327bbe9eaebd9322020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 20V, positivesplash10-0159-0900000000-b753f5e40fab4c8f70922020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 30V, positivesplash10-00lr-0900000000-c9321c59320cacc256da2020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 40V, positivesplash10-001i-0900000000-11d29a227bda097d127c2020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 50V, positivesplash10-001i-0900000000-7e088dfb25fbf5322cae2020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 24V, positivesplash10-0159-0900000000-66c374cc807fdd5fc9882020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT 17V, negativesplash10-02t9-0910000000-6ad88fdea0ea1ddc87812020-08-04View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0090000000-cf623673de668657f3112016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udl-0190000000-392883a85c2c2015b0c32016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-044i-9500000000-499b35d8d5d2f169387d2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-4090000000-770d5ba68ba065242bf72016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-2190000000-82b6362d6ef9385de1d22016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0bti-9200000000-2b339e51e2cf38532f752016-08-03View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThis is a man-made compound that is used as a pesticide.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID213027
ChEMBL IDCHEMBL259727
ChemSpider ID184723
KEGG IDC18508
UniProt IDNot Available
OMIM ID
ChEBI ID39177
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D3815.pdf
General ReferencesNot Available
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Cytochrome P450 2C9
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.03 uMCLZD_CYP2C9_6CellzDirect
AC500.03 uMCLZD_CYP2C9_6CellzDirect
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
2. 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
AC501.48 uMBSK_LPS_Eselectin_upBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
3. Epidermal growth factor receptor
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_hDFCGF_EGFR_upBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
4. 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
5. 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
AC503.02 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
6. 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_SM3C_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
7. Urokinase plasminogen activator surface receptor
General Function:
Urokinase plasminogen activator receptor activity
Specific Function:
Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.
Gene Name:
PLAUR
Uniprot ID:
Q03405
Molecular Weight:
36977.62 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.44 uMBSK_BE3C_uPAR_upBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
8. Neuronal acetylcholine receptor subunit alpha-2
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:
CHRNA2
Uniprot ID:
Q15822
Molecular Weight:
59764.82 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.02 uMNVS_LGIC_hNNR_NBungSensNovascreen
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 ]