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Identification
NameUrokinase
Accession NumberDB00013  (BIOD00030, BTD00030)
Typebiotech
Groupsapproved, investigational, withdrawn
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

Protein structureDb00013
Protein chemical formulaC1376H2145N383O406S18
Protein average weight31126.5000
Sequences
>DB00013 sequence
KPSSPPEELKFQCGQKTLRPRFKIIGGEFTTIENQPWFAAIYRRHRGGSVTYVCGGSLMS
PCWVISATHCFIDYPKKEDYIVYLGRSRLNSNTQGEMKFEVENLILHKDYSADTLAHHND
IALLKIRSKEGRCAQPSRTIQTICLPSMYNDPQFGTSCEITGFGKENSTDYLYPEQLKMT
VVKLISHRECQQPHYYGSEVTTKMLCAADPQWKTDSCQGDSGGPLVCSLQGRMTLTGIVS
WGRGCALKDKPGVYTRVSHFLPWIRSHTKEENGLAL
Download FASTA Format
Synonyms
SynonymLanguageCode
U-plasminogen activatorNot AvailableNot Available
uPANot AvailableNot Available
Urokinase-type plasminogen activator precursorNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AbbokinaseAbbott Laboratories
KinlyticMicrobix Biosystems Inc.
Brand mixturesNot Available
Categories
CAS number9039-53-6
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationUrokinase can be used for the treatment of pulminary embolism, coronary artery thrombosis, IV catheter clearance, and venous and arterial blood clots.
PharmacodynamicsUrokinase is used for the treatment of pulmonary embolisms. The low molecular weight form of human urokinase consists of an A chain of 2,000 daltons linked by a sulfhydryl bond to a B chain of 30,400 daltons. Urokinase is an enzyme (protein) produced by the kidney, and found in the urine. There are two forms of urokinase which differ in molecular weight but have similar clinical effects. Urokinase is the low molecular weight form. Urokinase acts on the endogenous fibrinolytic system. It converts plasminogen to the enzyme plasmin. Plasmin degrades fibrin clots as well as fibrinogen and some other plasma proteins.
Mechanism of actionUrokinase 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Proteolysis

Route of eliminationUrokinase administered by intravenous infusion is rapidly cleared by the liver. Small fractions of the administered dose are excreted in bile and urine
Half life12 minutes. Small fractions of the administered dose are excreted in bile and urine
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Urokinase Action PathwayDrug actionSMP00284
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
Manufacturers
  • Microbix biosystems inc
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous
PricesNot Available
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point76 °C at pH 4.5Nowak, U.K. et al., Biochemistry 33:2951-2960 (1994)
hydrophobicity-0.466Not Available
isoelectric point8.66Not Available
References
Synthesis Reference

Koji Sasaki, Yasukazu Harada, “Urokinase preparation for oral administration.” U.S. Patent US4258030, issued November, 1975.

US4258030
General Reference
  1. Housley C: Contract purchasing means a buyer’s market. Dimens Health Serv. 1976 Apr;53(4):16, 19-20. Pubmed
External Links
ResourceLink
UniProtP00749
GenbankX02419
PharmGKBPA451836
Drug Product Database749702
RxListhttp://www.rxlist.com/cgi/pharmclips2.cgi?keyword=%20Abbokinase%AE
Drugs.comhttp://www.drugs.com/mtm/urokinase.html
WikipediaUrokinase
ATC CodesB01AD04
AHFS Codes
  • 20:12.20
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AprotininAprotonin may antagonize the effect of Urokinase. Monitor for decreased effects of Urokinase.
Drotrecogin alfaIncreased risk of bleeding.
Ginkgo bilobaIncreased risk of bleeding.
GinsengIncreased risk of bleeding.
Food InteractionsNot Available

Targets

1. Plasminogen

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: activator

Components

Name UniProt ID Details
Plasminogen P00747 Details

References:

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Urokinase plasminogen activator surface receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Components

Name UniProt ID Details
Urokinase plasminogen activator surface receptor Q03405 Details

References:

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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

3. Urokinase-type plasminogen activator

Kind: protein

Organism: Human

Pharmacological action: yes

Components

Name UniProt ID Details
Urokinase-type plasminogen activator P00749 Details

References:

  1. Bell WR: Present-day thrombolytic therapy: therapeutic agents—pharmacokinetics and pharmacodynamics. Rev Cardiovasc Med. 2002;3 Suppl 2:S34-44. Pubmed
  2. 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
  3. 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
  4. 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
  5. 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

4. Tissue-type plasminogen activator

Kind: protein

Organism: Human

Pharmacological action: yes

Components

Name UniProt ID Details
Tissue-type plasminogen activator P00750 Details

References:

  1. 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
  2. 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
  3. 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
  4. Wells RG, Havens PL: Intrapleural fibrinolysis for parapneumonic effusion and empyema in children. Radiology. 2003 Aug;228(2):370-8. Pubmed
  5. 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

5. Plasminogen activator inhibitor 1

Kind: protein

Organism: Human

Pharmacological action: yes

Components

Name UniProt ID Details
Plasminogen activator inhibitor 1 P05121 Details

References:

  1. 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
  2. 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
  3. Hellgren M: Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost. 2003 Apr;29(2):125-30. Pubmed
  4. 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
  5. 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

6. Plasminogen activator inhibitor 2

Kind: protein

Organism: Human

Pharmacological action: yes

Components

Name UniProt ID Details
Plasminogen activator inhibitor 2 P05120 Details

References:

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

7. Plasma serine protease inhibitor

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Plasma serine protease inhibitor P05154 Details

References:

  1. 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
  2. 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
  3. 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

8. Low-density lipoprotein receptor-related protein 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low-density lipoprotein receptor-related protein 2 P98164 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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
  3. 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
  4. 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
  5. 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

9. Suppressor of tumorigenicity 14 protein

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Suppressor of tumorigenicity 14 protein Q9Y5Y6 Details

References:

  1. 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
  2. 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

10. Nidogen-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Nidogen-1 P14543 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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
  3. 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

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Drug created on June 13, 2005 07:24 / Updated on January 20, 2014 16:58