Banner
Identification
Name Urokinase
Accession Number DB00013 (BIOD00030, BTD00030)
Type biotech
Groups approved
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 structure Db00013
Display: 3D Structure
Protein chemical formula C1376H2145N383O406S18
Protein average weight 31126.5000
Sequences 
>DB00013 sequence
KPSSPPEELKFQCGQKTLRPRFKIIGGEFTTIENQPWFAAIYRRHRGGSVTYVCGGSLMS
PCWVISATHCFIDYPKKEDYIVYLGRSRLNSNTQGEMKFEVENLILHKDYSADTLAHHND
IALLKIRSKEGRCAQPSRTIQTICLPSMYNDPQFGTSCEITGFGKENSTDYLYPEQLKMT
VVKLISHRECQQPHYYGSEVTTKMLCAADPQWKTDSCQGDSGGPLVCSLQGRMTLTGIVS
WGRGCALKDKPGVYTRVSHFLPWIRSHTKEENGLAL

FASTA
Synonyms
U-plasminogen activator
uPA
Urokinase-type plasminogen activator precursor
Salts Not Available
Brand names
Name Company
Abbokinase Abbott Laboratories
Kinlytic Microbix Biosystems Inc.
Brand mixtures Not Available
Categories
  • Thrombolytic Agents
CAS number 9039-53-6
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures 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.
Pharmacodynamics Urokinase 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 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
Volume of distribution Not Available
Protein binding Not Available
Metabolism 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
Half life 12 minutes. Small fractions of the administered dose are excreted in bile and urine
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00284 Urokinase Pathway SMP00284
Pharmacoeconomics
Manufacturers
  • Microbix biosystems inc
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Prices Not Available
Patents Not Available
Properties
State liquid
Experimental Properties
Property Value Source
melting point 76 °C at pH 4.5 Nowak, U.K. et al., Biochemistry 33:2951-2960 (1994)
hydrophobicity -0.466 Not Available
isoelectric point 8.66 Not Available
References
Synthesis Reference Not Available
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
Resource Link
UniProt P00749 Link_out
Genbank X02419 Link_out
PharmGKB PA451836 Link_out
Drug Product Database 749702 Link_out
RxList http://www.rxlist.com/cgi/pharmclips2.cgi?keyword=%20Abbokinase%AE Link_out
Drugs.com http://www.drugs.com/mtm/urokinase.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Urokinase Link_out
ATC Codes
  • B01AD04
AHFS Codes
  • 20:12.20
PDB Entries
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug 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

1. Plasminogen

Pharmacological action: yes
Actions: activator

Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo

Organism class: human
UniProt ID: P00747 Link_out
Gene: PLG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes

Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form

Organism class: human
UniProt ID: Q03405 Link_out
Gene: PLAUR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes

Specifically cleave the zymogen plasminogen to form the active enzyme plasmin

Organism class: human
UniProt ID: P00749 Link_out
Gene: PLAU Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes

Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. Play a direct role in facilitating neuronal migration

Organism class: human
UniProt ID: P00750 Link_out
Gene: PLAT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes

This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, and protein C. Its rapid interaction with TPA may function as a major control point in the regulation of fibrinolysis

Organism class: human
UniProt ID: P05121 Link_out
Gene: SERPINE1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes

Inhibits urokinase-type plasminogen activator. The monocyte derived PAI-2 is distinct from the endothelial cell- derived PAI-1

Organism class: human
UniProt ID: P05120 Link_out
Gene: SERPINB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Inhibits activated protein C as well as plasminogen activators

Organism class: human
UniProt ID: P05154 Link_out
Gene: SERPINA5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

May participate in regulation of parathyroid-hormone and para-thyroid-hormone-related protein release

Organism class: human
UniProt ID: P98164 Link_out
Gene: LRP2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 protein 14

Pharmacological action: unknown

Degrades extracellular matrix. Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site

Organism class: human
UniProt ID: Q9Y5Y6 Link_out
Gene: ST14 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Sulfated glycoprotein widely distributed in basement membranes and tightly associated with laminin. Also binds to collagen IV and perlecan. It probably has a role in cell- extracellular matrix interactions

Organism class: human
UniProt ID: P14543 Link_out
Gene: NID1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on September 29, 2010 14:34