Thiophanate-methyl (T3D3934)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (11)XML
Targets (11)
Record Information
Version2.0
Creation Date2013-04-25 07:56:55 UTC
Update Date2014-12-24 20:26:34 UTC
Accession NumberT3D3934
Identification
Common NameThiophanate-methyl
ClassSmall Molecule
DescriptionThiophanate-Methyl (TM) is a systemic fungicide. It was first registered to be used as a fungicide by the EPA in 1973. It is effective against a wide range of fungal pathogens including: eyespot and other diseases of cereals; scab on apples and pears; Monilia disease and Gloeosporim rot on apples; Monilia app. On stone fruit; Canker on fruit trees; powdery mildews on pome fruit, stone fruit, vegetables, cucurbits, strawberries, vines, roses. Thiophanate methyl is also used on almonds, pecans, tea, coffee, peanuts, soya beans, tobacco, chestnuts, sugar cane, citrus fruit, figs, hops, mulberries, and many other crops.
Compound Type
  • Amine
  • Carbamate
  • Ester
  • Ether
  • Fungicide
  • Organic Compound
  • Pesticide
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
1,2-Di-(3-methoxycarbonyl-2-thioureido)benzene
Thiophanic acid-methyl
Chemical FormulaC12H14N4O4S2
Average Molecular Mass342.394 g/mol
Monoisotopic Mass342.046 g/mol
CAS Registry Number23564-05-8
IUPAC Namemethyl N-{[2-({[(methoxycarbonyl)amino]methanethioyl}amino)phenyl]carbamothioyl}carbamate
Traditional Namezyban
SMILESCOC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC
InChI IdentifierInChI=1S/C12H14N4O4S2/c1-19-11(17)15-9(21)13-7-5-3-4-6-8(7)14-10(22)16-12(18)20-2/h3-6H,1-2H3,(H2,13,15,17,21)(H2,14,16,18,22)
InChI KeyInChIKey=QGHREAKMXXNCOA-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassNot Available
Direct ParentBenzene and substituted derivatives
Alternative Parents
Substituents
  • Monocyclic benzene moiety
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Imine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
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 Solubility0.0058 g/LALOGPS
logP1.57ALOGPS
logP2.78ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)7.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area100.72 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity91.5 m³·mol⁻¹ChemAxon
Polarizability33.1 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 - NA , positivesplash10-001m-0493000000-9206bd309beff0fefcd72020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - NA , positivesplash10-001j-0692000000-181d532e1d669a8b39532020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - NA , positivesplash10-0udi-0900000000-04ba0cfb08ba0f0d14ed2020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - NA , positivesplash10-0udi-0900000000-fa1543d36d143517e0762020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - NA , positivesplash10-0udi-0900000000-12b59ca94144d9c8552e2020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 10V, positivesplash10-0006-0239000000-e04c531367d91a9db3cb2020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 20V, positivesplash10-0udi-0910000000-67902a0d481dfdebca272020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 30V, positivesplash10-0udi-0900000000-7efcc2fc958d0975d8702020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 50V, positivesplash10-0udi-0900000000-eef649baa1d657401cbd2020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 28V, positivesplash10-0udi-0900000000-6a3e84442d9748f38f902020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - NA , negativesplash10-0002-0900000000-5797ac3e11dd48f289222020-08-04View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-066r-1900000000-154dfa6211b96dcbf00b2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-05mk-0900000000-c60fb4df2799cc31230a2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-052b-0900000000-a6e1d001b11feaadae822021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-052b-0900000000-02ac28374832932d3f312021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-0002-0900000000-abe097dd1b3cccb658ea2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-0002-0900000000-b1bfab9fbf58ee6059e22021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-0udi-1900000000-7fd6e318ca5e49d6883b2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0udi-3900000000-1c5b759187e151a2ca672021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0069000000-42b2b7d1fe773f7c71a12016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0mji-2191000000-5e4ad4f9e36741f393992016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0aou-6890000000-07aa9f75bd43da357cc82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-066r-6797000000-f9d5a25515c64f560fd92016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-06di-4971000000-bccd4bec96ce78b2b40f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05n0-9850000000-055d02c535528ae533cb2016-08-03View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, DMSO-d6, experimental)Not Available2014-10-20View Spectrum
1D NMR13C NMR Spectrum (1D, 100.40 MHz, DMSO-d6, experimental)Not Available2014-10-20View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC.
Uses/SourcesThis is a man-made compound that is used as a pesticide.
Minimum Risk LevelNot Available
Health EffectsThiophanate-methyl is likely a human carcinogen. It increases of risk of liver tumours in mice. Thyroid/parathyroid weights were increased The developmental toxicity studies showed the decreased fetal body weight and increases in skeletal variations in the fetuses of rabbits exposed to thiophanate-methyl. It induced histopathological damages in rat thyroid and adrenal glands.
SymptomsThiophanate-methyl can cause skin, eye and respiratory irritation, shortness of breath, chest pains, burning eyes, dizziness, and fatigue.
TreatmentRinse dermal exposure with water, irrigate exposed eyes with water, remove the contaminated clothing. Intubate the patients with altered mental status or airway injury. Treat acidosis and seizures. Patients should be treated with activated charcoal after large ingestions of thiophanate-methyl if they can drink the charcoal.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID3032791
ChEMBL IDCHEMBL487187
ChemSpider ID2297683
KEGG IDC14432
UniProt IDNot Available
OMIM ID
ChEBI ID35014
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D3934.pdf
General References
  1. De Falco M, Sciarrillo R, Capaldo A, Russo T, Gay F, Valiante S, Varano L, Laforgia V: The effects of the fungicide methyl thiophanate on adrenal gland morphophysiology of the lizard, Podarcis sicula. Arch Environ Contam Toxicol. 2007 Aug;53(2):241-8. Epub 2007 Jun 2. [17549544 ]
  2. EPA - Thiophanate-methyl [Link]
  3. Toxnet - Thiophanate-methyl [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. 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
AC501.48 uMBSK_LPS_MCP1_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
2. Early activation antigen CD69
General Function:
Transmembrane signaling receptor activity
Specific Function:
Involved in lymphocyte proliferation and functions as a signal transmitting receptor in lymphocytes, natural killer (NK) cells, and platelets.
Gene Name:
CD69
Uniprot ID:
Q07108
Molecular Weight:
22559.25 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_SAg_CD69_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. Vascular cell adhesion protein 1
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_4H_VCAM1_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
4. 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
AC506.80 uMCLZD_CYP2B6_6CellzDirect
AC504.27 uMCLZD_CYP2B6_24CellzDirect
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. 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
6. 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
AC508.36 uMCLZD_CYP3A4_6CellzDirect
AC505.09 uMCLZD_CYP3A4_24CellzDirect
AC504.89 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
7. UDP-glucuronosyltransferase 1-1
General Function:
Steroid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular Weight:
59590.91 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.00 uMCLZD_UGT1A1_24CellzDirect
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. Bile salt sulfotransferase
General Function:
Sulfotransferase activity
Specific Function:
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfonation of steroids and bile acids in the liver and adrenal glands.
Gene Name:
SULT2A1
Uniprot ID:
Q06520
Molecular Weight:
33779.57 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.65 uMCLZD_SULT2A1_24CellzDirect
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
9. Cytochrome P450 1A1
General Function:
Vitamin d 24-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular Weight:
58164.815 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.83 uMCLZD_CYP1A1_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
10. Cytochrome P450 1A2
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.24 uMCLZD_CYP1A2_6CellzDirect
AC508.77 uMCLZD_CYP1A2_24CellzDirect
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
11. 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
AC507.28 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 ]