Details of the Drug

General Information of Drug (ID: DM6D7N8)

Drug Name

Propylthiouracil

Synonyms

propylthiouracil; 51-52-5; 6-Propyl-2-thiouracil; Propacil; Prothyran; Prothiurone; Procasil; Propycil; Thiuragyl; Protiural; Prothiucil; Prothycil; Propyl-Thiorist; Propyl-Thyracil; 2-Mercapto-6-propylpyrimidin-4-ol; 6-N-Propylthiouracil; Propythiouracil; Propilthiouracil; Propyl-Thiorit; Propylthiorit; 6-Propylthiouracil; Propylthiouracile; Thyreostat II; 6-propyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one; Propiltiouracilo; 6-N-Propyl-2-thiouracil; 6-Thio-4-propyluracil; PTU (thyreostatic); Propylthiouracilum; 4-Propyl-2-thiouracil; Procasil; Propiltiouracile; PROPYL THIOURACIL; Propiltiouracile [DCIT]; Thyreos tat ii; HC210060; Propiltiouracilo [INN-Spanish]; Propylthiouracil (TN); Propylthiouracile [INN-French]; Propylthiouracilum [INN-Latin]; Ptu(thyreostatic); T0517-6237; Thyreostat propyl-thyracil; Propylthiouracil [INN:BAN:JAN]; Propylthiouracil (JP15/USP/INN); 2,3-Dihydro-6-propyl-2-thioxo-4(1H)-pyrimidinone; 2-Mercapto-4-hydroxy-6-n-propylpyrimidine; 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-Hydroxy-2-mercapto-6-propylpyrimidine; 6 Propyl 2 Thiouracil; 6-(n-Propyl)-2-thiouracil; 6-Prop yl-2-thiouracil; 6-Propil-tiouracile; 6-Propil-tiouracile [Italian]; 6-Propyl-2-thio-2,4(1H,3H)-pyrimidinedione; 6-Propyl-2-thio-2,4(1H,3H)pyrimidinedione; 6-n-PROPYL-2-MERCAPTO-4-HYDROXYPYRIMIDINE; 6-propyl-2 thiouracil; 6-propyl-2-sulfanylidene-1H-pyrimidin-4-one; 6-propyl-2-sulfanylidene-2,3-dihydropyrimidin-4(1H)-one; 6-propyl-2-thiopyrimidine-2,4(1H,3H)-dione; Propyl thiouracile

Indication

Disease Entry	ICD 11	Status	REF
Hyperthyroidism	5A02	Approved	[1], [2], [3]

Therapeutic Class

Antithyroid Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

170.23

Topological Polar Surface Area (xlogp)

0.8

Rotatable Bond Count (rotbonds)

2

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

2

ADMET Property

Absorption: The drug is well absorbed after oral administration [4]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [5]
Bioavailability: 85% of drug becomes completely available to its intended biological destination(s) [6]
Clearance: The drug present in the plasma can be removed from the body at the rate of 3.1 mL/min/kg [7]
Half-life: The concentration or amount of drug in body reduced by one-half in 2 hours [7]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 75.5281 micromolar/kg/day [8]
Unbound Fraction: The unbound fraction of drug in plasma is 0.18% [7]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.34 L/kg [7]
Water Solubility: The ability of drug to dissolve in water is measured as 1.2 mg/mL [5]

Chemical Identifiers

Formula: C7H10N2OS
IUPAC Name: 6-propyl-2-sulfanylidene-1H-pyrimidin-4-one
Canonical SMILES: CCCC1=CC(=O)NC(=S)N1
InChI: InChI=1S/C7H10N2OS/c1-2-3-5-4-6(10)9-7(11)8-5/h4H,2-3H2,1H3,(H2,8,9,10,11)
InChIKey: KNAHARQHSZJURB-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 657298
ChEBI ID: CHEBI:8502
CAS Number: 51-52-5
DrugBank ID: DB00550
TTD ID: D00MIN
ACDINA ID: D00566

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Iodothyronine deiodinase type I (DIO1)	TTU3X26	IOD1_HUMAN	Inhibitor	[9]
Thyroid peroxidase (TPO)	TT52XDZ	PERT_HUMAN	Inhibitor	[10], [11]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Hyperthyroidism

ICD Disease Classification

5A02

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Thyroid peroxidase (TPO)	DTT	TPO	3.83E-01	1.09	1.43

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Propylthiouracil (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[14]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[15]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[16]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Cannabidiol.	Epileptic encephalopathy [8A62]	[17]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[18]
Efavirenz	DMC0GSJ	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Efavirenz.	Human immunodeficiency virus disease [1C60-1C62]	[19]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[20]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[21]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Propylthiouracil and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[22]
Methotrexate	DM2TEOL	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Methotrexate.	Leukaemia [2A60-2B33]	[17]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[23]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Idelalisib.	Mature B-cell leukaemia [2A82]	[24]
Clofarabine	DMCVJ86	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Clofarabine.	Mature B-cell lymphoma [2A85]	[25]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Leflunomide.	Rheumatoid arthritis [FA20]	[21]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[17]
Naltrexone	DMUL45H	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Naltrexone.	Substance abuse [6C40]	[26]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Docusate sodium	E00563	23673837	Surfactant
Sodium benzoate	E00432	517055	Antimicrobial preservative; lubricant
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Water	E00035	962	Solvent
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⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Propylthiouracil 50 mg tablet	50 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6650).
2	FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 006188.
3	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
5	BDDCS applied to over 900 drugs
6	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
7	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
8	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
9	Type 1 iodothyronine deiodinase is the major source of circulating T3 in hyperthyroidism: implications for therapy. Nat Clin Pract Endocrinol Metab. 2007 Nov;3(11):740-1.
10	Bioinorganic chemistry in thyroid gland: effect of antithyroid drugs on peroxidase-catalyzed oxidation and iodination reactions. Bioinorg Chem Appl. 2006:23214.
11	Theoretical aspects of the treatment with antithyroid drugs. Ann Endocrinol (Paris). 1994;55(1):1-5.
12	Diagnosis and treatment of thyrotoxicosis in childhood. A European questionnaire study. Eur J Endocrinol. 1994 Nov;131(5):467-73.
13	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2526).
14	Cerner Multum, Inc. "Australian Product Information.".
15	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
16	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
17	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
18	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
19	Elsharkawy AM, Schwab U, McCarron B, et al. "Efavirenz induced acute liver failure requiring liver transplantation in a slow drug metaboliser." J Clin Virol 58 (2013): 331-3. [PMID: 23763943]
20	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
21	Canadian Pharmacists Association.
22	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
23	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
24	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
25	Product Information. Clolar (clofarabine). sanofi-aventis, Bridgewater, NJ.
26	Product Information. ReVia (naltrexone). DuPont Pharmaceuticals, Wilmington, DE.