Propylthiouracil (T3D4712)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2014-09-11 02:06:03 UTC
Update Date2014-12-24 20:26:55 UTC
Accession NumberT3D4712
Identification
Common NamePropylthiouracil
ClassSmall Molecule
DescriptionPropylthiouracil is only found in individuals that have used or taken this drug. It is a thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. Propylthiouracil binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (1) and tri-iodothyronine (2), which are the main hormones produced by the thyroid gland. Therefore propylthiouracil effectively inhibits the production of new thyroid hormones.
Compound Type
  • Amide
  • Antimetabolite
  • Antithyroid Agent
  • Drug
  • Ester
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
2,3-dihydro-6-Propyl-2-thioxo-4(1H)-pyrimidinone
2-Mercapto-6-propyl-4-pyrimidone
2-Mercapto-6-propylpyrimid-4-one
2-Thio-4-oxo-6-propyl-1,3-pyrimidine
2-Thio-6-propyl-1,3-pyrimidin-4-one
4-Propyl-2-thiouracil
6-Propyl-2-thio-2,4(1H,3H)pyrimidinedione
6-Propyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one
6-Propylthiouracil
6-Thio-4-propyluracil
Antiroid
Procasil
Propacil
Propil
Propilracil
Propilthiouracil
Propiltiouracilo
Propycil
Propyl-Thiorist
Propyl-Thiorit
Propyl-Thyracil
Propylthiorit
Propylthiouracile
Propylthiouracilum
Propythiouracil
Proracyl
Prothiucil
Prothiurone
Prothuril
Prothycil
Prothyran
Protiural
PTU
Thiuragyl
Thyrosan
Tiotil
Tirostat
Uracil
Chemical FormulaC7H10N2OS
Average Molecular Mass170.232 g/mol
Monoisotopic Mass170.051 g/mol
CAS Registry Number51-52-5
IUPAC Name6-propyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidin-4-one
Traditional Namepropylthiouracil
SMILESCCCC1=CC(O)=NC(S)=N1
InChI IdentifierInChI=1S/C7H10N2OS/c1-2-3-5-4-6(10)9-7(11)8-5/h4H,2-3H2,1H3,(H2,8,9,10,11)
InChI KeyInChIKey=KNAHARQHSZJURB-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyrimidones. Pyrimidones are compounds that contain a pyrimidine ring, which bears a ketone. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentPyrimidones
Alternative Parents
Substituents
  • 2-thiopyrimidine
  • Pyrimidinethione
  • Thiopyrimidine
  • Pyrimidone
  • Hydropyrimidine
  • Heteroaromatic compound
  • Vinylogous amide
  • Lactam
  • Thiourea
  • Azacycle
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • 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 Point219°C
Boiling PointNot Available
Solubility1200 mg/L (at 25°C)
LogP0.4
Predicted Properties
PropertyValueSource
Water Solubility0.47 g/LALOGPS
logP1.53ALOGPS
logP1.2ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)8.09ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area41.13 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity48.9 m³·mol⁻¹ChemAxon
Polarizability17.79 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, Positivesplash10-0006-3900000000-31cf32b92bb0613f38642017-09-01View 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-qTof , Positivesplash10-00di-0900000000-6549521c2c4645bc95422017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-014i-0900000000-f857bb6ee86a6e7b0ab32017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-066r-7900000000-e5e5c265147935fdd8d22017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-9000000000-927304e1ff32407a8d182017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-9000000000-343c26fd83ebb89d346d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-9000000000-0d1467a930d2ddf9349b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00di-0900000000-0b376a1be2d2d48ad8752017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0fk9-0900000000-f095bd0fa6c365161ec92017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0900000000-2ce23fa0cb6ec6129e292017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00di-0900000000-9ee3b1971c716e9a4dc12017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00di-0900000000-7d9cf3791e4e7800916d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0ik9-5900000000-41be31a4c739b4ea29a42017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-03xr-9200000000-8eb9b68ae97914399fc02017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00di-1900000000-b867c06c7c74b627274c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-0900000000-6549521c2c4645bc95422017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-0a4i-9300000000-1c45f7c8a1ed2bb4ff1a2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-0a4i-9000000000-316f99d9fa451f830ecc2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-0a4i-9300000000-6e8260b8f96483c7a7252021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-0a4i-9000000000-acdbd4788bf0a434a52c2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-1900000000-c92d3e54c5a5d44238b62016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fk9-2900000000-02a40d3cf3fcf71171432016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0pbc-9100000000-d83421a35456bb2cd5162016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-2900000000-0171c0c7c9c5fd9b0d232016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-066u-9700000000-e296fd0e7563b2f97dd72016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9100000000-74e2c284c39ca64e90d42016-08-03View Spectrum
MSMass Spectrum (Electron Ionization)splash10-00dl-9800000000-dd34c50b7aa55979d5f22014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 90 MHz, DMSO-d6, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 15.09 MHz, DMSO-d6, experimental)Not Available2014-09-23View Spectrum
Toxicity Profile
Route of ExposureWell absorbed following oral administration.
Mechanism of ToxicityPropylthiouracil binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (1) and tri-iodothyronine (2), which are the main hormones produced by the thyroid gland. Therefore propylthiouracil effectively inhibits the production of new thyroid hormones.
MetabolismRoute of Elimination: Propylthiouracil is readily absorbed and is extensively metabolized. Approximately 35% of the drug is excreted in the urine, in intact and conjugated forms, within 24 hours. Half Life: 2 hours
Toxicity ValuesOral, rat: LD50 = 1250 mg/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (3)
Uses/SourcesUsed to manage hyperthyroidism which is due to an overactive thyroid gland (Grave's disease).
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00550
HMDB IDHMDB14690
PubChem Compound ID657298
ChEMBL IDCHEMBL1518
ChemSpider ID571424
KEGG IDC07569
UniProt IDNot Available
OMIM ID
ChEBI ID8502
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkPropylthiouracil
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Ellenhorn MJ and Barceloux DG (1988). Diagnosis and treatment of human poisoning. Medical Toxicology. New York, New York: Elsevier Science Publishing Company, Inc.
  2. Emsley, John (2001). Nature's Building Blocks: An A-Z Guide to the Elements. Oxford: Oxford University Press.
  3. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Thyroid peroxidase
General Function:
Peroxidase activity
Specific Function:
Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).
Gene Name:
TPO
Uniprot ID:
P07202
Molecular Weight:
102961.63 Da
References
  1. Sugawara M, Sugawara Y, Wen K: Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles. Thyroid. 1999 May;9(5):513-8. [10365684 ]
  2. Manzon RG, Holmes JA, Youson JH: Variable effects of goitrogens in inducing precocious metamorphosis in sea lampreys (Petromyzon marinus). J Exp Zool. 2001 Apr 15;289(5):290-303. [11241400 ]
  3. Ferreira AC, de Carvalho Cardoso L, Rosenthal D, de Carvalho DP: Thyroid Ca2+/NADPH-dependent H2O2 generation is partially inhibited by propylthiouracil and methimazole. Eur J Biochem. 2003 Jun;270(11):2363-8. [12755690 ]
  4. Schmutzler C, Bacinski A, Gotthardt I, Huhne K, Ambrugger P, Klammer H, Schlecht C, Hoang-Vu C, Gruters A, Wuttke W, Jarry H, Kohrle J: The ultraviolet filter benzophenone 2 interferes with the thyroid hormone axis in rats and is a potent in vitro inhibitor of human recombinant thyroid peroxidase. Endocrinology. 2007 Jun;148(6):2835-44. Epub 2007 Mar 22. [17379648 ]
  5. Taurog A, Dorris ML: A reexamination of the proposed inactivation of thyroid peroxidase in the rat thyroid by propylthiouracil. Endocrinology. 1989 Jun;124(6):3038-42. [2656250 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
2. Estrogen receptor
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.427 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC507.94 uMATG_ERE_CISAttagene
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 ]