DT-Web

DB00013 - Urokinase


Identification
Name Urokinase
Accession Number DB00013 (BIOD00030, BTD00030)
Type biotech
Description Low molecular weight form of human urokinase, that consists of an A chain of 2,000 daltons linked by a sulfhydryl bond to a B chain of 30,400 daltons. Recombinant urokinase plasminogen activator
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 31126.5000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication Urokinase can be used for the treatment of pulminary embolism, coronary artery thrombosis, IV catheter clearance, and venous and arterial blood clots.
Mechanism of action Urokinase acts on the endogenous fibrinolytic system. It cleaves the Arg-Val bond in plasminogen to produce active plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins.
Absorption Not Available
Protein binding Not Available
Biotransformation Proteolysis
Route of elimination Urokinase administered by intravenous infusion is rapidly cleared by the liver. Small fractions of the administered dose are excreted in bile and urine
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Aprotinin Aprotonin may antagonize the effect of Urokinase. Monitor for decreased effects of Urokinase.
Drotrecogin alfa Increased risk of bleeding.
Ginkgo biloba Increased risk of bleeding.
Ginseng Increased risk of bleeding.
Food Interactions Not Available

Targets


Plasminogen
Name Plasminogen
Gene Name PLG
Pharmacological action yes
Actions activator
References
  • Zhang X, Zhou H, Shen G, Liu Z, Hu Y, Wei W, Song S: Study on the mechanism of the annexin II-mediated co-assembly of t-PA and plasminogen. J Huazhong Univ Sci Technolog Med Sci. 2002;22(1):21-3, 76. - Pubmed
  • Lopez-Alemany R, Longstaff C, Hawley S, Mirshahi M, Fabregas P, Jardi M, Merton E, Miles LA, Felez J: Inhibition of cell surface mediated plasminogen activation by a monoclonal antibody against alpha-Enolase. Am J Hematol. 2003 Apr;72(4):234-42. - Pubmed
  • Hashimoto M, Oiwa K, Matsuo O, Ueshima S, Okada K, Okada Y, Okamoto S, Giddings JC, Yamamoto J: Suppression of argatroban-induced endogenous thrombolysis by PKSI-527, and antibodies to TPA and UPA, evaluated in a rat arterial thrombolysis model. Thromb Haemost. 2003 May;89(5):820-5. - Pubmed
  • Guda K, Claffey KP, Dong M, Nambiar PR, Rosenberg DW: Defective processing of the transforming growth factor-beta1 in azoxymethane-induced mouse colon tumors. Mol Carcinog. 2003 May;37(1):51-9. - Pubmed
  • Chang H, Shyu KG, Lin S, Wang BW, Liu YC, Lee CC: Cell adhesion induces the plasminogen activator inhibitor-1 gene expression through phosphatidylinositol 3-kinase/Akt activation in anchorage dependent cells. Cell Commun Adhes. 2002 Sep-Dec;9(5-6):239-47. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.4728
Urokinase plasminogen activator surface receptor
Name Urokinase plasminogen activator surface receptor
Gene Name PLAUR
Pharmacological action yes
Actions Not Available
References
  • Czekay RP, Aertgeerts K, Curriden SA, Loskutoff DJ: Plasminogen activator inhibitor-1 detaches cells from extracellular matrices by inactivating integrins. J Cell Biol. 2003 Mar 3;160(5):781-91. - Pubmed
  • Fuchs T, Allgayer H: Transcriptional regulation of the urokinase receptor (u-PAR)--a central molecule of invasion and metastasis. Biol Chem. 2003 May;384(5):755-61. - Pubmed
  • Kanse SM, Chavakis T, Al-Fakhri N, Hersemeyer K, Monard D, Preissner KT: Reciprocal regulation of urokinase receptor (CD87)-mediated cell adhesion by plasminogen activator inhibitor-1 and protease nexin-1. J Cell Sci. 2004 Jan 26;117(Pt 3):477-85. Epub 2003 Dec 16. - Pubmed
  • Beaufort N, Leduc D, Rousselle JC, Magdolen V, Luther T, Namane A, Chignard M, Pidard D: Proteolytic regulation of the urokinase receptor/CD87 on monocytic cells by neutrophil elastase and cathepsin G. J Immunol. 2004 Jan 1;172(1):540-9. - Pubmed
  • Guerrero J, Santibanez JF, Gonzalez A, Martinez J: EGF receptor transactivation by urokinase receptor stimulus through a mechanism involving Src and matrix metalloproteinases. Exp Cell Res. 2004 Jan 1;292(1):201-8. - Pubmed
  • Gutova M, Najbauer J, Gevorgyan A, Metz MZ, Weng Y, Shih CC, Aboody KS: Identification of uPAR-positive chemoresistant cells in small cell lung cancer. PLoS One. 2007 Feb 28;2(2):e243. - Pubmed
DTHybrid score 1.2835
Urokinase-type plasminogen activator
Name Urokinase-type plasminogen activator
Gene Name PLAU
Pharmacological action yes
Actions Not Available
References
  • Bell WR: Present-day thrombolytic therapy: therapeutic agents--pharmacokinetics and pharmacodynamics. Rev Cardiovasc Med. 2002;3 Suppl 2:S34-44. - Pubmed
  • Gamberi G, Serra M, Ragazzini P, Magagnoli G, Pazzaglia L, Ponticelli F, Ferrari C, Zanasi M, Bertoni F, Picci P, Benassi MS: Identification of markers of possible prognostic value in 57 giant cell tumors of bone. Oncol Rep. 2003 Mar-Apr;10(2):351-6. - Pubmed
  • Zhang G, Kim H, Cai X, Lopez-Guisa JM, Alpers CE, Liu Y, Carmeliet P, Eddy AA: Urokinase receptor deficiency accelerates renal fibrosis in obstructive nephropathy. J Am Soc Nephrol. 2003 May;14(5):1254-71. - Pubmed
  • Chang H, Shyu KG, Lin S, Wang BW, Liu YC, Lee CC: Cell adhesion induces the plasminogen activator inhibitor-1 gene expression through phosphatidylinositol 3-kinase/Akt activation in anchorage dependent cells. Cell Commun Adhes. 2002 Sep-Dec;9(5-6):239-47. - Pubmed
  • Wielockx B, Libert C: Serine proteases of the fibrinolysis pathway are not involved in lethal hepatitis and fibrinogen breakdown induced by tumor necrosis factor. Cytokine. 2003 Mar 21;21(6):281-5. - Pubmed
DTHybrid score 1.8983
Tissue-type plasminogen activator
Name Tissue-type plasminogen activator
Gene Name PLAT
Pharmacological action yes
Actions Not Available
References
  • Chang H, Shyu KG, Lin S, Wang BW, Liu YC, Lee CC: Cell adhesion induces the plasminogen activator inhibitor-1 gene expression through phosphatidylinositol 3-kinase/Akt activation in anchorage dependent cells. Cell Commun Adhes. 2002 Sep-Dec;9(5-6):239-47. - Pubmed
  • Lindholt JS, Jorgensen B, Shi GP, Henneberg EW: Relationships between activators and inhibitors of plasminogen, and the progression of small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2003 Jun;25(6):546-51. - Pubmed
  • Aleman C, Alegre J, Monasterio J, Segura RM, Armadans L, Angles A, Varela E, Ruiz E, Fernandez de Sevilla T: Association between inflammatory mediators and the fibrinolysis system in infectious pleural effusions. Clin Sci (Lond). 2003 Nov;105(5):601-7. - Pubmed
  • Wells RG, Havens PL: Intrapleural fibrinolysis for parapneumonic effusion and empyema in children. Radiology. 2003 Aug;228(2):370-8. - Pubmed
  • Stief TW, Bunder R, Richter A, Maisch B, Renz H, Fareed J: In vitro simulation of therapeutic plasmatic fibrinolysis. Clin Appl Thromb Hemost. 2003 Jul;9(3):211-20. - Pubmed
DTHybrid score 1.194
Plasminogen activator inhibitor 1
Name Plasminogen activator inhibitor 1
Gene Name SERPINE1
Pharmacological action yes
Actions Not Available
References
  • Gamberi G, Serra M, Ragazzini P, Magagnoli G, Pazzaglia L, Ponticelli F, Ferrari C, Zanasi M, Bertoni F, Picci P, Benassi MS: Identification of markers of possible prognostic value in 57 giant cell tumors of bone. Oncol Rep. 2003 Mar-Apr;10(2):351-6. - Pubmed
  • Shetty S, Bdeir K, Cines DB, Idell S: Induction of plasminogen activator inhibitor-1 by urokinase in lung epithelial cells. J Biol Chem. 2003 May 16;278(20):18124-31. Epub 2003 Mar 17. - Pubmed
  • Hellgren M: Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost. 2003 Apr;29(2):125-30. - Pubmed
  • Chang H, Shyu KG, Lin S, Wang BW, Liu YC, Lee CC: Cell adhesion induces the plasminogen activator inhibitor-1 gene expression through phosphatidylinositol 3-kinase/Akt activation in anchorage dependent cells. Cell Commun Adhes. 2002 Sep-Dec;9(5-6):239-47. - Pubmed
  • Gerstein ES, Shcherbakov AM, Kaz'min AI, Ognerubov NA, Kushlinskii NE: [Urokinase and tissue type plasminogen activators and their type-1 inhibitor (PAI-1) in gastric cancer] Vopr Onkol. 2003;49(2):165-9. - Pubmed
DTHybrid score 1.2721
Plasminogen activator inhibitor 2
Name Plasminogen activator inhibitor 2
Gene Name SERPINB2
Pharmacological action yes
Actions Not Available
References
  • Swartz JM, Bystrom J, Dyer KD, Nitto T, Wynn TA, Rosenberg HF: Plasminogen activator inhibitor-2 (PAI-2) in eosinophilic leukocytes. J Leukoc Biol. 2004 Oct;76(4):812-9. Epub 2004 Jul 26. - Pubmed
  • Wygrecka M, Markart P, Ruppert C, Kuchenbuch T, Fink L, Bohle RM, Grimminger F, Seeger W, Gunther A: Compartment- and cell-specific expression of coagulation and fibrinolysis factors in the murine lung undergoing inhalational versus intravenous endotoxin application. Thromb Haemost. 2004 Sep;92(3):529-40. - Pubmed
  • Iglesias D, Alegre J, Aleman C, Ruiz E, Soriano T, Armadans LI, Segura RM, Angles A, Monasterio J, de Sevilla TF: Metalloproteinases and tissue inhibitors of metalloproteinases in exudative pleural effusions. Eur Respir J. 2005 Jan;25(1):104-9. - Pubmed
  • Grebenchtchikov N, Maguire TM, Riisbro R, Geurts-Moespot A, O'Donovan N, Schmitt M, McGreal G, McDermott E, O'Higgins N, Brunner N, Sweep CG, Duffy MJ: Measurement of plasminogen activator system components in plasma and tumor tissue extracts obtained from patients with breast cancer: an EORTC Receptor and Biomarker Group collaboration. Oncol Rep. 2005 Jul;14(1):235-9. - Pubmed
  • Fernandez-Soria V, Lleonart ME, Diaz-Fuertes M, Villuendas R, Sanchez-Prieto R, Fabra A, Ramon Y Cajal S: Adenovirus E1A orchestrates the urokinase-plasminogen activator system and upregulates PAI-2 expression, supporting a tumor suppressor effect. Int J Oncol. 2006 Jan;28(1):143-8. - Pubmed
DTHybrid score 0.7854
Plasma serine protease inhibitor
Name Plasma serine protease inhibitor
Gene Name SERPINA5
Pharmacological action unknown
Actions Not Available
References
  • Uhrin P, Schofer C, Zaujec J, Ryban L, Hilpert M, Weipoltshammer K, Jerabek I, Pirtzkall I, Furtmuller M, Dewerchin M, Binder BR, Geiger M: Male fertility and protein C inhibitor/plasminogen activator inhibitor-3 (PCI): localization of PCI in mouse testis and failure of single plasminogen activator knockout to restore spermatogenesis in PCI-deficient mice. Fertil Steril. 2007 Oct;88(4S):1049-1057. Epub 2007 Apr 16. - Pubmed
  • Espana F, Navarro S, Medina P, Zorio E, Estelles A: The role of protein C inhibitor in human reproduction. Semin Thromb Hemost. 2007 Feb;33(1):41-5. - Pubmed
  • Odet F, Guyot R, Leduque P, Le Magueresse-Battistoni B: Evidence for similar expression of protein C inhibitor and the urokinase-type plasminogen activator system during mouse testis development. Endocrinology. 2004 Mar;145(3):1481-9. Epub 2003 Nov 26. - Pubmed
DTHybrid score 0.7168
Low-density lipoprotein receptor-related protein 2
Name Low-density lipoprotein receptor-related protein 2
Gene Name LRP2
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Kanalas JJ: Effect of the nephritogenic autoantibody of Heymann's nephritis on plasminogen-binding to gp330 and activation by urokinase. Biochim Biophys Acta. 1993 Nov 25;1225(1):101-6. - Pubmed
  • Kanalas JJ: Analysis of plasmin binding and urokinase activation of plasminogen bound to the Heymann nephritis autoantigen, gp330. Arch Biochem Biophys. 1992 Dec;299(2):255-60. - Pubmed
  • Korenberg JR, Argraves KM, Chen XN, Tran H, Strickland DK, Argraves WS: Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1). Genomics. 1994 Jul 1;22(1):88-93. - Pubmed
DTHybrid score 0.7556
Suppressor of tumorigenicity protein 14
Name Suppressor of tumorigenicity protein 14
Gene Name ST14
Pharmacological action unknown
Actions Not Available
References
  • Suzuki M, Kobayashi H, Kanayama N, Saga Y, Suzuki M, Lin CY, Dickson RB, Terao T: Inhibition of tumor invasion by genomic down-regulation of matriptase through suppression of activation of receptor-bound pro-urokinase. J Biol Chem. 2004 Apr 9;279(15):14899-908. Epub 2004 Jan 27. - Pubmed
  • Kirchhofer D, Peek M, Li W, Stamos J, Eigenbrot C, Kadkhodayan S, Elliott JM, Corpuz RT, Lazarus RA, Moran P: Tissue expression, protease specificity, and Kunitz domain functions of hepatocyte growth factor activator inhibitor-1B (HAI-1B), a new splice variant of HAI-1. J Biol Chem. 2003 Sep 19;278(38):36341-9. Epub 2003 Jun 18. - Pubmed
DTHybrid score 0.721
Nidogen-1
Name Nidogen-1
Gene Name NID1
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Stephens RW, Aumailley M, Timpl R, Reisberg T, Tapiovaara H, Myohanen H, Murphy-Ullrich J, Vaheri A: Urokinase binding to laminin-nidogen. Structural requirements and interactions with heparin. Eur J Biochem. 1992 Aug 1;207(3):937-42. - Pubmed
DTHybrid score 0.7101

Predictions


Id Partner name Gene Name Score
595 Fibrinogen alpha chain FGA 0.7023
3825 Tetranectin CLEC3B 0.189
3826 Keratin, type II cytoskeletal 8 KRT8 0.1888
2111 Annexin A2 ANXA2 0.1888
3176 Trypsin-1 PRSS1 0.1854
1516 Calnexin CANX 0.1644
3831 Low-density lipoprotein receptor-related protein 1 LRP1 0.1514
3830 Calreticulin CALR 0.1504
2353 Apolipoprotein(a) LPA 0.1477
2889 Kallikrein-6 KLK6 0.1204
2947 Trypsin sprT 0.1204
54 Prothrombin F2 0.1144
1959 Platelet factor 4 PF4 0.1116
3865 Serpin B6 SERPINB6 0.1116
1986 Ceruloplasmin CP 0.1114
2021 Thrombomodulin THBD 0.1089
308 30S ribosomal protein S12 rpsL 0.1066
6704 30S ribosomal protein S12 rpsL 0.1066
4814 Copper transport protein ATOX1 ATOX1 0.1046
3211 3,2-trans-enoyl-CoA isomerase, mitochondrial DCI 0.1045
19 Coagulation factor VIII F8 0.0969
2072 Endothelial protein C receptor PROCR 0.0963
46 Coagulation factor V F5 0.0963
1193 Proteinase-activated receptor 1 F2R 0.0899
1245 Vitamin K-dependent protein S PROS1 0.0886
2886 Trypsin-3 PRSS3 0.0794
6020 Aldehyde oxidase AOX1 0.0785
448 Vitamin K-dependent gamma-carboxylase GGCX 0.0749
2876 Membrane-bound lytic murein transglycosylase B mltB 0.0726
3133 UDP-galactopyranose mutase glf 0.0725
5099 UDP-galactopyranose mutase glf 0.0725
3849 Insulin-like growth factor-binding protein 7 IGFBP7 0.0725
1949 Carboxypeptidase E CPE 0.0725
2009 Protein NOV homolog NOV 0.0725
3847 Neuroendocrine convertase 2 PCSK2 0.0725
3850 Synaptotagmin-like protein 4 SYTL4 0.0725
3848 Neuroendocrine convertase 1 PCSK1 0.0725
3846 Retinoblastoma-associated protein RB1 0.0725
1729 Solute carrier family 22 member 6 SLC22A6 0.0704
1812 Kallikrein-1 KLK1 0.0676
2155 Insulin-degrading enzyme IDE 0.0646
2236 Casein kinase II subunit alpha CSNK2A1 0.0636
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.0573
958 Insulin-like growth factor 1 receptor IGF1R 0.0519
1243 Cathepsin D CTSD 0.0516
36 Insulin receptor INSR 0.0506
723 Cytosolic phospholipase A2 PLA2G4A 0.05
3844 HLA class II histocompatibility antigen, DQ(6) alpha chain HLA-DQA2 0.0401
6011 Chymotrypsinogen B CTRB1 0.0359
4200 Cytochrome P450 1A2 CYP1A2 0.025
527 Prostacyclin receptor PTGIR 0.0222
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.021
4109 cAMP-specific 3',5'-cyclic phosphodiesterase 4C PDE4C 0.0208
73 Prostaglandin E2 receptor, EP1 subtype PTGER1 0.0203
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0189
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0184
3851 Serine protease hepsin HPN 0.0175
1971 cAMP-specific 3',5'-cyclic phosphodiesterase 4A PDE4A 0.0174
2358 cAMP-specific 3',5'-cyclic phosphodiesterase 4D PDE4D 0.0173
541 cAMP-specific 3',5'-cyclic phosphodiesterase 4B PDE4B 0.0159
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0141
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0133
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0131
238 Peroxisome proliferator-activated receptor gamma PPARG 0.013
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0127
6221 Steroid hormone receptor ERR1 ESRRA 0.0127
1457 Long-chain-fatty-acid--CoA ligase 4 ACSL4 0.0116
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.01
6177 UDP-glucuronosyltransferase 1-10 UGT1A10 0.01
3809 Estrogen-related receptor gamma ESRRG 0.0097
4924 Cytochrome P450 2C8 CYP2C8 0.0091
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.009
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.0088
6085 Fatty acid-binding protein, intestinal FABP2 0.0088
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0088
6016 Cytochrome P450 2C19 CYP2C19 0.0088
6180 UDP-glucuronosyltransferase 2B4 UGT2B4 0.0087
273 Apoptosis regulator Bcl-2 BCL2 0.0087
4757 Cytochrome P450 2C9 CYP2C9 0.0084
776 Bile salt export pump ABCB11 0.007
3811 Cytochrome P450 19A1 CYP19A1 0.0067
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0063
387 Amiloride-sensitive amine oxidase [copper-containing] ABP1 0.0062
7187 Amiloride-sensitive amine oxidase [copper-containing] ABP1 0.0062
827 Sodium/hydrogen exchanger 1 SLC9A1 0.0062
6024 Cytochrome P450 1A1 CYP1A1 0.0058
1024 Solute carrier family 22 member 11 SLC22A11 0.0056
749 Amiloride-sensitive cation channel 1, neuronal ACCN1 0.0056
2164 Multidrug resistance-associated protein 4 ABCC4 0.0055
6107 Cytochrome P450 3A7 CYP3A7 0.0055
6030 Cytochrome P450 2B6 CYP2B6 0.0054
862 Multidrug resistance-associated protein 1 ABCC1 0.0052
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0051
4118 Cytochrome P450 3A5 CYP3A5 0.0051
290 Prostaglandin G/H synthase 2 PTGS2 0.0051
550 Amiloride-sensitive sodium channel subunit delta SCNN1D 0.005
27 Amiloride-sensitive sodium channel subunit beta SCNN1B 0.005
552 Amiloride-sensitive sodium channel subunit gamma SCNN1G 0.005
213 Amiloride-sensitive sodium channel subunit alpha SCNN1A 0.005
389 Amiloride-sensitive cation channel 2, neuronal ACCN2 0.0049
6142 Solute carrier family 22 member 8 SLC22A8 0.0049
20 Prostaglandin G/H synthase 1 PTGS1 0.0048
587 Serum albumin ALB 0.0044
4512 Cytochrome P450 3A4 CYP3A4 0.004
1588 Multidrug resistance protein 1 ABCB1 0.0037
833 Organic cation/carnitine transporter 1 SLC22A4 0.0031
6144 Solute carrier family 22 member 2 SLC22A2 0.0026
6145 Solute carrier family 22 member 1 SLC22A1 0.0026
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