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]
Thyroid crisis	N.A.	Approved	[2]
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Therapeutic Class

Antithyroid Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

170.23

Logarithm of the Partition Coefficient (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 []
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
Bioavailability: 85% of drug becomes completely available to its intended biological destination(s) [4]
Clearance: The drug present in the plasma can be removed from the body at the rate of 3.1 mL/min/kg [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 2 hours [5]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 75.5281 micromolar/kg/day [6]
Unbound Fraction: The unbound fraction of drug in plasma is 0.18% [5]
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 [5]
Water Solubility: The ability of drug to dissolve in water is measured as 1.2 mg/mL [3]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Vasculitis	Not Available	ancA?	OTTU3FKC	[7]
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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

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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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	[8]
Thyroid peroxidase (TPO)	TT52XDZ	PERT_HUMAN	Inhibitor	[9]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Gene/Protein Processing	[10]
Basic salivary proline-rich protein 1 (PRB1)	OTV0SYMD	PRP1_HUMAN	Drug Response	[11]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Gene/Protein Processing	[12]
Carbonic anhydrase 6 (CA6)	OTIX56CJ	CAH6_HUMAN	Drug Response	[11]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Gene/Protein Processing	[13]
DNA-binding protein inhibitor ID-2 (ID2)	OT0U1D53	ID2_HUMAN	Gene/Protein Processing	[12]
DNA-binding protein inhibitor ID-3 (ID3)	OTUULW5Z	ID3_HUMAN	Gene/Protein Processing	[12]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Gene/Protein Processing	[14]
Integrin beta-5 (ITGB5)	OT21MF51	ITB5_HUMAN	Gene/Protein Processing	[12]
Krueppel-like factor 9 (KLF9)	OTBFEJRQ	KLF9_HUMAN	Gene/Protein Processing	[12]

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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]	[15]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[16]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[17]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Cannabidiol.	Epileptic encephalopathy [8A62]	[18]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[19]
Efavirenz	DMC0GSJ	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Efavirenz.	Human immunodeficiency virus disease [1C60-1C62]	[20]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[21]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[22]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Propylthiouracil and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[23]
Methotrexate	DM2TEOL	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Methotrexate.	Leukaemia [2A60-2B33]	[18]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[24]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Idelalisib.	Mature B-cell leukaemia [2A82]	[25]
Clofarabine	DMCVJ86	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Clofarabine.	Mature B-cell lymphoma [2A85]	[26]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Leflunomide.	Rheumatoid arthritis [FA20]	[22]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[18]
Naltrexone	DMUL45H	Moderate	Increased risk of hepatotoxicity by the combination of Propylthiouracil and Naltrexone.	Substance abuse [6C40]	[27]
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⏷ Show the Full List of 16 DDI Information of This Drug

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

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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	Propylthiouracil FDA Label
3	BDDCS applied to over 900 drugs
4	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6	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
7	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
8	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.
9	Bioinorganic chemistry in thyroid gland: effect of antithyroid drugs on peroxidase-catalyzed oxidation and iodination reactions. Bioinorg Chem Appl. 2006:23214.
10	Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
11	Responsiveness to 6-n-propylthiouracil (PROP) is associated with salivary levels of two specific basic proline-rich proteins in humans. PLoS One. 2012;7(2):e30962. doi: 10.1371/journal.pone.0030962. Epub 2012 Feb 1.
12	Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
13	Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways. Toxicol Appl Pharmacol. 2012 Apr 1;260(1):81-8. doi: 10.1016/j.taap.2012.01.029. Epub 2012 Feb 8.
14	A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
15	Cerner Multum, Inc. "Australian Product Information.".
16	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
17	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
18	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
19	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
20	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]
21	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
22	Canadian Pharmacists Association.
23	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
24	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]
25	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
26	Product Information. Clolar (clofarabine). sanofi-aventis, Bridgewater, NJ.
27	Product Information. ReVia (naltrexone). DuPont Pharmaceuticals, Wilmington, DE.