DT-Web

DB00550 - Propylthiouracil


Identification
Name Propylthiouracil
Accession Number DB00550 (APRD00297)
Type small molecule
Description 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)
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 170.232
Groups approved
Monoisotopic Weight 170.051383642
Pharmacology
Indication Used to manage hyperthyroidism which is due to an overactive thyroid gland (Grave's disease).
Mechanism of action 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 (T4) and tri-iodothyronine (T3), which are the main hormones produced by the thyroid gland. Therefore propylthiouracil effectively inhibits the production of new thyroid hormones.
Absorption Well absorbed following oral administration.
Protein binding 82%
Biotransformation Not Available
Route 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.
Toxicity Oral, rat: LD50 = 1250 mg/kg.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Acenocoumarol The anti-thyroid agent, propylthiouracil, may decrease the anticoagulant effect of acenocoumarol.
Anisindione The anti-thyroid agent, propylthiouracil, may decrease the anticoagulant effect of anisindione.
Dicumarol The anti-thyroid agent, propylthiouracil, may decrease the anticoagulant effect of dicumarol.
Digoxin The antithyroid agent may increase the effect of digoxin.
Warfarin Propylthiouracil may decrease the anticoagulant effect of warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if propylthiouracil is initiated, discontinued or dose changed.
Food Interactions
  • Take at the same time everyday.

Targets


Thyroid peroxidase
Name Thyroid peroxidase
Gene Name TPO
Pharmacological action yes
Actions inhibitor
References
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.5412

Enzymes


Myeloperoxidase
Name Myeloperoxidase
Gene Name MPO
Actions inhibitor
References
  • Lee E, Miki Y, Katsura H, Kariya K: Mechanism of inactivation of myeloperoxidase by propylthiouracil. Biochem Pharmacol. 1990 May 1;39(9):1467-71. - Pubmed
  • Kariya K, Lee E, Hirouchi M: Relationship between leukopenia and bone marrow myeloperoxidase in the rat treated with propylthiouracil. Jpn J Pharmacol. 1984 Oct;36(2):217-22. - Pubmed
  • Zhang AH, Chen M, Gao Y, Zhao MH, Wang HY: Inhibition of oxidation activity of myeloperoxidase (MPO) by propylthiouracil (PTU) and anti-MPO antibodies from patients with PTU-induced vasculitis. Clin Immunol. 2007 Feb;122(2):187-93. Epub 2006 Oct 27. - Pubmed
  • Lee E, Hirouchi M, Hosokawa M, Sayo H, Kohno M, Kariya K: Inactivation of peroxidases of rat bone marrow by repeated administration of propylthiouracil is accompanied by a change in the heme structure. Biochem Pharmacol. 1988 Jun 1;37(11):2151-3. - Pubmed
DTHybrid score 0.4348
Dopamine beta-hydroxylase
Name Dopamine beta-hydroxylase
Gene Name DBH
Actions inhibitor
References
  • Hidaka H, Nagasaka A: Inhibition of dopamine beta-hydroxylase by anti-thyroid agents, methimazole and propylthiouracil. Biochem Pharmacol. 1977 Jun 1;26(11):1092-3. - Pubmed
DTHybrid score 0.3384

Predictions


Id Partner name Gene Name Score
3811 Cytochrome P450 19A1 CYP19A1 0.0874
4757 Cytochrome P450 2C9 CYP2C9 0.051
6013 Cytochrome P450 2E1 CYP2E1 0.0452
290 Prostaglandin G/H synthase 2 PTGS2 0.0391
147 Aldehyde dehydrogenase, mitochondrial ALDH2 0.0387
758 Thyroid hormone receptor alpha THRA 0.0349
4200 Cytochrome P450 1A2 CYP1A2 0.034
4512 Cytochrome P450 3A4 CYP3A4 0.032
1736 Somatostatin SST 0.0311
4186 Neuropeptide Y receptor type 2 NPY2R 0.0311
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0307
346 Thyroid hormone receptor beta-1 THRB 0.0288
6150 Solute carrier organic anion transporter family member 4C1 SLCO4C1 0.0288
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0284
20 Prostaglandin G/H synthase 1 PTGS1 0.0268
6016 Cytochrome P450 2C19 CYP2C19 0.0268
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0257
309 Antithrombin-III SERPINC1 0.0251
3997 Cytochrome P450 24A1, mitochondrial CYP24A1 0.0239
4118 Cytochrome P450 3A5 CYP3A5 0.0233
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0224
275 Arachidonate 5-lipoxygenase ALOX5 0.0215
503 Somatostatin receptor type 1 SSTR1 0.0214
4119 Cytochrome P450 2D6 CYP2D6 0.021
723 Cytosolic phospholipase A2 PLA2G4A 0.021
3866 Serum amyloid A protein SAA1 0.0209
1932 Apolipoprotein E APOE 0.0208
1200 AMBP protein AMBP 0.0208
54 Prothrombin F2 0.0207
61 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0201
2644 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0201
2710 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0201
3872 Somatostatin receptor type 5 SSTR5 0.02
6008 Somatostatin receptor type 2 SSTR2 0.02
6030 Cytochrome P450 2B6 CYP2B6 0.0198
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.019
856 Vitamin D3 receptor VDR 0.0189
6020 Aldehyde oxidase AOX1 0.0188
118 Organic cation/carnitine transporter 2 SLC22A5 0.0187
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0183
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0182
713 Sodium-dependent dopamine transporter SLC6A3 0.0175
3941 Amine oxidase [flavin-containing] A MAOA 0.0174
3939 Amine oxidase [flavin-containing] B MAOB 0.0171
239 Coagulation factor X F10 0.0167
5718 Cytochrome P450 2A6 CYP2A6 0.0166
3839 Phytanoyl-CoA dioxygenase, peroxisomal PHYH 0.0165
115 Penicillin-binding protein 2 mrdA 0.016
6069 Penicillin-binding protein 2 mrdA 0.016
6118 Penicillin-binding protein 2 penA 0.016
6187 Penicillin-binding protein 2 pbpA 0.016
6686 Penicillin-binding protein 2 pbp2 0.016
6939 Penicillin-binding protein 2 mrdA 0.016
7163 Penicillin-binding protein 2 pbpA 0.016
867 Penicillin-binding protein 3 pbpC 0.016
6119 Penicillin-binding protein 3 pbp3 0.016
7154 Penicillin-binding protein 3 pbp3 0.016
7157 Penicillin-binding protein 3 LMHCC_2184 0.016
7162 Penicillin-binding protein 3 pbpB 0.016
7172 Penicillin-binding protein 3 pbp3 0.016
6012 Tryptophan 2,3-dioxygenase TDO2 0.0155
3954 Egl nine homolog 2 EGLN2 0.0155
3948 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2 ALKBH2 0.0155
3956 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 ALKBH3 0.0155
3946 Hypothetical protein DKFZp686H15154 OGFOD2 0.0155
189 Solute carrier family 23 member 1 SLC23A1 0.0155
3962 Egl nine homolog 3 EGLN3 0.0155
3935 Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 PLOD2 0.0155
3966 Putative HIF-prolyl hydroxylase PH-4 P4HTM 0.0155
3953 2-oxoglutarate and iron-dependent oxygenase domain containing 1 OGFOD1 0.0155
3958 Jumonji/ARID domain-containing protein 1D KDM5D 0.0155
6165 Copper-transporting ATPase 1 ATP7A 0.0132
6163 Copper-transporting ATPase 2 ATP7B 0.0132
633 Penicillin-binding proteins 1A/1B pbpA 0.0132
3964 Trimethyllysine dioxygenase, mitochondrial TMLHE 0.0126
3940 Gamma-butyrobetaine dioxygenase BBOX1 0.0126
97 Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 PLOD1 0.0126
3938 Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3 PLOD3 0.0126
6146 High affinity copper uptake protein 1 SLC31A1 0.0125
6144 Solute carrier family 22 member 2 SLC22A2 0.0124
6147 Solute carrier family 22 member 3 SLC22A3 0.0122
4152 Superoxide dismutase [Cu-Zn] SOD1 0.0121
6270 Group IIE secretory phospholipase A2 PLA2G2E 0.0121
908 Glutathione S-transferase theta-1 GSTT1 0.0119
3943 Peptidyl-glycine alpha-amidating monooxygenase PAM 0.0119
2038 Inhibitor of nuclear factor kappa-B kinase subunit beta IKBKB 0.0119
3960 Egl nine homolog 1 EGLN1 0.0116
3949 Prolyl 3-hydroxylase 2 LEPREL1 0.0113
3951 Prolyl 3-hydroxylase 3 LEPREL2 0.0113
3945 Prolyl 3-hydroxylase 1 LEPRE1 0.0113
3810 Catechol O-methyltransferase COMT 0.0107
67 Prolyl 4-hydroxylase subunit alpha-1 P4HA1 0.0107
896 Glutathione S-transferase Mu 1 GSTM1 0.0105
163 D(1B) dopamine receptor DRD5 0.0105
6145 Solute carrier family 22 member 1 SLC22A1 0.0101
3947 Xanthine dehydrogenase/oxidase XDH 0.0099
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0099
432 D(4) dopamine receptor DRD4 0.0099
6161 Probable low affinity copper uptake protein 2 SLC31A2 0.0098
638 D(3) dopamine receptor DRD3 0.0095
904 Glutathione S-transferase P GSTP1 0.0094
2485 Hyaluronate lyase SP_0314 0.0093
3172 Hyaluronate lyase hylB 0.0093
6847 Lactase-phlorizin hydrolase LCT 0.0093
2245 Xylose isomerase xylA 0.0091
2253 Xylose isomerase xylA 0.0091
2260 Xylose isomerase xylA 0.0091
2431 Xylose isomerase xylA 0.0091
23 D(1A) dopamine receptor DRD1 0.0086
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0083
238 Peroxisome proliferator-activated receptor gamma PPARG 0.008
831 D(2) dopamine receptor DRD2 0.0079
6024 Cytochrome P450 1A1 CYP1A1 0.0079
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0076
1729 Solute carrier family 22 member 6 SLC22A6 0.0075
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0075
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0071
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0069
109 Mitochondrial carnitine/acylcarnitine carrier protein CACL SLC25A29 0.0067
636 Mitochondrial carnitine/acylcarnitine carrier protein SLC25A20 0.0067
3601 Dihydropteroate synthase 1 folP1 0.0065
3807 Dihydropteroate synthase 1 folP1 0.0065
3808 Dihydropteroate synthase 2 folP2 0.0065
122 P2Y purinoceptor 12 P2RY12 0.0062
6036 Eosinophil peroxidase EPX 0.0059
6168 Solute carrier family 22 member 16 SLC22A16 0.0058
200 Carnitine O-palmitoyltransferase 2, mitochondrial CPT2 0.0058
451 Carnitine O-palmitoyltransferase I, liver isoform CPT1A 0.0058
3830 Calreticulin CALR 0.0057
412 Peroxisomal carnitine O-octanoyltransferase CROT 0.0057
551 Carnitine O-acetyltransferase CRAT 0.0057
6034 Hydroxyindole O-methyltransferase ASMT 0.0055
6035 Nuclear receptor ROR-beta RORB 0.0055
4924 Cytochrome P450 2C8 CYP2C8 0.0054
1898 Cytochrome P450 1B1 CYP1B1 0.0053
6142 Solute carrier family 22 member 8 SLC22A8 0.0051
765 Indoleamine 2,3-dioxygenase IDO1 0.0047
6102 Arylamine N-acetyltransferase 2 NAT2 0.0045
362 Melatonin receptor type 1B MTNR1B 0.0045
571 Melatonin receptor type 1A MTNR1A 0.0045
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0041
4604 Liver carboxylesterase 1 CES1 0.0037
833 Organic cation/carnitine transporter 1 SLC22A4 0.0035
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0033
6106 Cytochrome P450 2C18 CYP2C18 0.0033
465 Calmodulin CALM1 0.0029
468 Cytochrome P450 4A11 CYP4A11 0.0026
6137 Multidrug resistance-associated protein 6 ABCC6 0.0026
6107 Cytochrome P450 3A7 CYP3A7 0.0024
136 Estrogen receptor ESR1 0.0024
6136 Multidrug resistance-associated protein 5 ABCC5 0.0024
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0021
3923 Cholinesterase BCHE 0.0018
1588 Multidrug resistance protein 1 ABCB1 0.0013
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