propylthiouracil 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
uracil derivatives used as thyroid antagonists 2308 51-52-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • propylthiouracil
  • 6-n-Propylthiouracil
  • procasil
  • propacil
  • prothiurone
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. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)
  • Molecular weight: 170.23
  • Formula: C7H10N2OS
  • CLOGP: 0.97
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 2
  • TPSA: 41.13
  • ALOGS: -2.56
  • ROTB: 2
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.10 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 1.20 mg/mL Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 75.53 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 85 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.34 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 3.10 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.18 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.30 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 0.676 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.946 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 71.614 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 7.396 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 84.180 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 50.350 % High 1
herg hERG pIC50 3.838 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.706 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.396 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 65.790 % High 1
kinase-safety-class ACVR2A,ACVR2B,ACVRL1,ALK,AURKA,AURKB,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK5,CDK9,CHEK1,CSF1R,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GRK3,GSK3B,IGF1R,IKBKB,IRAK1,ITK,JAK1,JAK2,KIT,MAP3K1,MAP3K14,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAPK10,MAPK12,MAPK7,MAPK9,MAPKAPK2,MARK4,MELK,MET,MTOR,NTRK2,PAK4,PDK1,PDK2,PDK4,PDPK1,PIK3CB,PIK3CD,PIM1,PIM2,PIM3,PLK1,PRKCD,PRKDC,SGK1,SIK2,SIK3,STK33,SYK,TEK,TTK,ULK1,ULK2 71
kinase-selectivity-class ACVR2A,ACVR2B,AXL,BRAF,CAMK2D,CDK16,CDK9,DDR1,DYRK1B,ERBB2,GRK2,GRK3,MAP2K3,MAP3K14,MAP3K21,MAPK7,MARK4,PIK3CB,PRKDC,SIK2,SIK3,STK33,TEK,TTK,ULK1 25
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 5.117 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.449 High 1
mh-clint Mouse hepatocyte intrinsic clearance 8.337 High 1
mppb Mouse plasma protein binding (% unbound) 81.010 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 1.349 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 69.370 % High 1
rat-kpuu-brain Rat brain Kpuu 0.100 % High 1
rh-clint Rat hepatocyte intrinsic clearance 3.170 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 98.340 % High 1
rppb Rat plasma protein binding (% unbound) 62.350 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 944.061 uM High 1

Approvals:

DateAgencyCompanyOrphan
July 28, 1947 FDA DAVA PHARMS INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Anti-neutrophil cytoplasmic antibody positive vasculitis 340.44 32.12 65 2857 3928 90621597
Antineutrophil cytoplasmic antibody positive 148.56 32.12 25 2897 728 90624797
Exposure during pregnancy 142.78 32.12 91 2831 238319 90387206
Thyrotoxic crisis 136.29 32.12 25 2897 1206 90624319
Hyperthyroidism 121.09 32.12 38 2884 18272 90607253
Agranulocytosis 104.11 32.12 40 2882 34962 90590563
Vasculitis 97.44 32.12 34 2888 22659 90602866
Foetal exposure during pregnancy 89.45 32.12 38 2884 42937 90582588
Liver transplant 75.39 32.12 17 2905 2300 90623225
Acute hepatic failure 75.07 32.12 28 2894 22533 90602992
Cardiogenic shock 62.29 32.12 25 2897 24443 90601082
Maternal exposure during pregnancy 47.28 32.12 58 2864 360005 90265520
Goitre congenital 43.25 32.12 5 2917 5 90625520
Premature delivery 42.42 32.12 22 2900 38740 90586785
Pulmonary renal syndrome 40.43 32.12 8 2914 577 90624948
Cardiac arrest 38.98 32.12 30 2892 104905 90520620
Hypothyroidism 38.53 32.12 23 2899 53104 90572421
Pulmonary alveolar haemorrhage 37.75 32.12 12 2910 5986 90619539
Drug ineffective 37.42 32.12 113 2809 1384185 89241340
Drug reaction with eosinophilia and systemic symptoms 34.93 32.12 20 2902 42738 90582787
Immature respiratory system 34.29 32.12 5 2917 55 90625470
Haemoptysis 33.86 32.12 18 2904 33302 90592223
Congenital hypothyroidism 33.71 32.12 6 2916 243 90625282
Dysmorphism 33.29 32.12 9 2913 2559 90622966
Premature baby 32.61 32.12 16 2906 25061 90600464

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hyperthyroidism 84.37 39.20 24 777 14317 42606217
Foetal exposure during pregnancy 66.48 39.20 27 774 47284 42573250
Obstructive pancreatitis 49.14 39.20 9 792 746 42619788
Cardiogenic shock 48.84 39.20 20 781 35620 42584914
Thyrotoxic crisis 48.24 39.20 9 792 825 42619709
Goitre 41.19 39.20 9 792 1821 42618713
Goitre congenital 39.54 39.20 4 797 0 42620534

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Anti-neutrophil cytoplasmic antibody positive vasculitis 372.36 29.69 73 3311 5344 110580571
Thyrotoxic crisis 174.14 29.69 33 3351 2007 110583908
Hyperthyroidism 156.43 29.69 51 3333 29210 110556705
Exposure during pregnancy 140.30 29.69 78 3306 167346 110418569
Antineutrophil cytoplasmic antibody positive 112.53 29.69 27 3357 5049 110580866
Cardiogenic shock 99.79 29.69 44 3340 57294 110528621
Vasculitis 94.44 29.69 37 3347 35836 110550079
Agranulocytosis 93.50 29.69 43 3341 61717 110524198
Acute hepatic failure 86.89 29.69 35 3349 36433 110549482
Drug ineffective 68.98 29.69 146 3238 1520394 109065521
Liver transplant 55.24 29.69 15 3369 4574 110581341
Cardiac arrest 49.75 29.69 44 3340 196709 110389206
Premature delivery 42.20 29.69 20 3364 30612 110555303
Obstructive pancreatitis 40.26 29.69 9 3375 1232 110584683
Maternal exposure during pregnancy 38.39 29.69 43 3341 254840 110331075
Pulmonary renal syndrome 37.95 29.69 8 3376 833 110585082
Hepatotoxicity 35.88 29.69 23 3361 63377 110522538
Glomerulonephritis rapidly progressive 35.08 29.69 9 3375 2206 110583709
Drug-induced liver injury 34.68 29.69 29 3355 120038 110465877
Goitre 33.86 29.69 11 3373 6193 110579722
Off label use 33.55 29.69 111 3273 1500074 109085841
Drug reaction with eosinophilia and systemic symptoms 30.51 29.69 23 3361 82072 110503843

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC H03BA02 SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS
THYROID THERAPY
ANTITHYROID PREPARATIONS
Thiouracils
MeSH PA D000963 Antimetabolites
MeSH PA D006727 Hormone Antagonists
MeSH PA D013956 Antithyroid Agents
FDA MoA N0000175917 Thyroid Hormone Synthesis Inhibitors
FDA EPC N0000175918 Thyroid Hormone Synthesis Inhibitor
CHEBI has role CHEBI:22586 antioxidants
CHEBI has role CHEBI:35221 antimetabolite
CHEBI has role CHEBI:49020 hormone antagonists
CHEBI has role CHEBI:50671 antithyroid drugs
CHEBI has role CHEBI:50903 carcinogen
CHEBI has role CHEBI:61908 nitric oxide synthase inhibitors
CHEBI has role CHEBI:74529 antidotes to acetaminophen poisoning

Related Drugs by ATC class:

H03BA Thiouracils 2 drugs
benzylthiouracilmethylthiouracil

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Thyrotoxic crisis indication 29028009 DOID:12837
Hyperthyroidism indication 34486009 DOID:7998
Necrotizing vasculitis contraindication 11791001
Hyperbilirubinemia contraindication 14783006 DOID:2741
Agranulocytosis contraindication 17182001 DOID:12987
Hypothyroidism contraindication 40930008 DOID:1459
Interstitial pneumonia contraindication 64667001
Leukopenia contraindication 84828003 DOID:615
Pancytopenia contraindication 127034005 DOID:12450
Liver function tests abnormal contraindication 166603001
Drug-induced hepatitis contraindication 235876009
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Bone marrow depression contraindication 307762000




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.52 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Thyroid peroxidase Enzyme INHIBITOR IC50 5.06 WOMBAT-PK CHEMBL
Type I iodothyronine deiodinase Enzyme INHIBITOR CHEMBL CHEMBL
Myeloperoxidase Enzyme IC50 5.55 CHEMBL
Lactoperoxidase Enzyme IC50 5.12 CHEMBL
Taste receptor type 2 member 38 GPCR EC50 5.70 CHEMBL

External reference:

IDSource
4017432 VUID
N0000145820 NUI
D00562 KEGG_DRUG
4017432 VANDF
C0033511 UMLSCUI
CHEBI:8502 CHEBI
CHEMBL1518 ChEMBL_ID
DB00550 DRUGBANK_ID
D011441 MESH_DESCRIPTOR_UI
657298 PUBCHEM_CID
4184 INN_ID
6650 IUPHAR_LIGAND_ID
721M9407IY UNII
8794 RXNORM
2256 MMSL
5376 MMSL
d00361 MMSL
002137 NDDF
3814009 SNOMEDCT_US
387203007 SNOMEDCT_US
3CJ PDB_CHEM_ID
721M9407IY INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Propylthiouracil HUMAN PRESCRIPTION DRUG LABEL 1 0480-9242 TABLET 50 mg ORAL ANDA 23 sections
Propylthiouracil HUMAN PRESCRIPTION DRUG LABEL 1 0480-9242 TABLET 50 mg ORAL ANDA 23 sections
Propylthiouracil Human Prescription Drug Label 1 33342-314 TABLET 50 mg ORAL ANDA 22 sections
Propylthiouracil HUMAN PRESCRIPTION DRUG LABEL 1 42254-010 TABLET 50 mg ORAL ANDA 18 sections
Propylthiouracil HUMAN PRESCRIPTION DRUG LABEL 1 62135-606 TABLET 50 mg ORAL ANDA 14 sections
Propylthiouracil HUMAN PRESCRIPTION DRUG LABEL 1 67253-651 TABLET 50 mg ORAL NDA 23 sections
Propylthiouracil HUMAN PRESCRIPTION DRUG LABEL 1 68084-964 TABLET 50 mg ORAL NDA 24 sections
PROPYLTHIOURACIL HUMAN PRESCRIPTION DRUG LABEL 1 70752-171 TABLET 50 mg ORAL ANDA 21 sections
PROPYLTHIOURACIL HUMAN PRESCRIPTION DRUG LABEL 1 71335-2901 TABLET 50 mg ORAL ANDA 21 sections
PROPYLTHIOURACIL HUMAN PRESCRIPTION DRUG LABEL 1 72162-2072 TABLET 50 mg ORAL ANDA 21 sections