Identification

Name
Urokinase
Accession Number
DB00013  (BTD00030, BIOD00030)
Type
Biotech
Groups
Approved, Investigational, Withdrawn
Biologic Classification
Protein Based Therapies
Blood factors
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
Protein chemical formula
C1376H2145N383O406S18
Protein average weight
31126.5 Da
Sequences
>DB00013 sequence
KPSSPPEELKFQCGQKTLRPRFKIIGGEFTTIENQPWFAAIYRRHRGGSVTYVCGGSLMS
PCWVISATHCFIDYPKKEDYIVYLGRSRLNSNTQGEMKFEVENLILHKDYSADTLAHHND
IALLKIRSKEGRCAQPSRTIQTICLPSMYNDPQFGTSCEITGFGKENSTDYLYPEQLKMT
VVKLISHRECQQPHYYGSEVTTKMLCAADPQWKTDSCQGDSGGPLVCSLQGRMTLTGIVS
WGRGCALKDKPGVYTRVSHFLPWIRSHTKEENGLAL
Download FASTA Format
Synonyms
  • U-plasminogen activator
  • uPA
  • Urokinase-type plasminogen activator precursor
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Kinlytic (urokinase for Injection)Powder, for solution250000 unitIntravenousMicrobix Biosystems Inc1988-12-312009-10-28Canada
Kinlytic Open-cathPowder, for solution5000 unitIntravenousMicrobix Biosystems Inc1991-12-312009-10-28Canada
International/Other Brands
Abbokinase (Abbott Laboratories) / Kinlytic (Microbix Biosystems Inc.)
Categories
UNII
83G67E21XI
CAS number
9039-53-6

Pharmacology

Indication

Urokinase can be used for the treatment of pulminary embolism, coronary artery thrombosis, IV catheter clearance, and venous and arterial blood clots.

Structured Indications
Not Available
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.

TargetActionsOrganism
APlasminogen
activator
Human
AUrokinase plasminogen activator surface receptorNot AvailableHuman
AUrokinase-type plasminogen activatorNot AvailableHuman
ATissue-type plasminogen activatorNot AvailableHuman
APlasminogen activator inhibitor 1Not AvailableHuman
APlasminogen activator inhibitor 2Not AvailableHuman
UPlasma serine protease inhibitorNot AvailableHuman
ULow-density lipoprotein receptor-related protein 2Not AvailableHuman
USuppressor of tumorigenicity 14 proteinNot AvailableHuman
UNidogen-1Not AvailableHuman
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
PathwayCategory
Urokinase Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbciximabUrokinase may increase the anticoagulant activities of Abciximab.Approved
AcenocoumarolUrokinase may increase the anticoagulant activities of Acenocoumarol.Approved
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Urokinase.Approved, Vet Approved
AloxiprinThe risk or severity of adverse effects can be increased when Aloxiprin is combined with Urokinase.Experimental
AlprostadilAlprostadil may increase the anticoagulant activities of Urokinase.Approved, Investigational
Aminosalicylic AcidThe risk or severity of adverse effects can be increased when Aminosalicylic Acid is combined with Urokinase.Approved
AnagrelideAnagrelide may increase the anticoagulant activities of Urokinase.Approved
AncrodUrokinase may increase the anticoagulant activities of Ancrod.Investigational
AndrographolideAndrographolide may increase the anticoagulant activities of Urokinase.Investigational
Antithrombin III humanUrokinase may increase the anticoagulant activities of Antithrombin III human.Approved
ApixabanUrokinase may increase the anticoagulant activities of Apixaban.Approved
AprotininThe therapeutic efficacy of Urokinase can be decreased when used in combination with Aprotinin.Approved, Withdrawn
ArdeparinUrokinase may increase the anticoagulant activities of Ardeparin.Approved, Withdrawn
ArgatrobanUrokinase may increase the anticoagulant activities of Argatroban.Approved, Investigational
AzelastineAzelastine may increase the anticoagulant activities of Urokinase.Approved
BalsalazideThe risk or severity of adverse effects can be increased when Balsalazide is combined with Urokinase.Approved, Investigational
BecaplerminUrokinase may increase the anticoagulant activities of Becaplermin.Approved, Investigational
BeraprostBeraprost may increase the anticoagulant activities of Urokinase.Investigational
BivalirudinUrokinase may increase the anticoagulant activities of Bivalirudin.Approved, Investigational
BuflomedilBuflomedil may increase the anticoagulant activities of Urokinase.Experimental
ButylphthalideButylphthalide may increase the anticoagulant activities of Urokinase.Investigational
CangrelorCangrelor may increase the anticoagulant activities of Urokinase.Approved
Carbaspirin calciumThe risk or severity of adverse effects can be increased when Carbaspirin calcium is combined with Urokinase.Experimental
CertoparinUrokinase may increase the anticoagulant activities of Certoparin.Approved
CilostazolCilostazol may increase the anticoagulant activities of Urokinase.Approved
Citric AcidUrokinase may increase the anticoagulant activities of Citric Acid.Nutraceutical, Vet Approved
ClopidogrelClopidogrel may increase the anticoagulant activities of Urokinase.Approved, Nutraceutical
CloricromenCloricromen may increase the anticoagulant activities of Urokinase.Experimental
DalteparinUrokinase may increase the anticoagulant activities of Dalteparin.Approved
DanaparoidUrokinase may increase the anticoagulant activities of Danaparoid.Approved, Withdrawn
DarexabanUrokinase may increase the anticoagulant activities of Darexaban.Investigational
DefibrotideDefibrotide may increase the anticoagulant activities of Urokinase.Approved, Investigational
dersalazineThe risk or severity of adverse effects can be increased when dersalazine is combined with Urokinase.Investigational
DesirudinUrokinase may increase the anticoagulant activities of Desirudin.Approved
DextranUrokinase may increase the anticoagulant activities of Dextran.Approved, Vet Approved
Dextran 40Urokinase may increase the anticoagulant activities of Dextran 40.Approved
Dextran 70Urokinase may increase the anticoagulant activities of Dextran 70.Approved
Dextran 75Urokinase may increase the anticoagulant activities of Dextran 75.Approved
DicoumarolUrokinase may increase the anticoagulant activities of Dicoumarol.Approved
DiflunisalThe risk or severity of adverse effects can be increased when Diflunisal is combined with Urokinase.Approved
DipyridamoleDipyridamole may increase the anticoagulant activities of Urokinase.Approved
Edetic AcidUrokinase may increase the anticoagulant activities of Edetic Acid.Approved, Vet Approved
EdoxabanUrokinase may increase the anticoagulant activities of Edoxaban.Approved
EnoxaparinUrokinase may increase the anticoagulant activities of Enoxaparin.Approved
EpinastineEpinastine may increase the anticoagulant activities of Urokinase.Approved, Investigational
EplivanserinEplivanserin may increase the anticoagulant activities of Urokinase.Investigational
eplivanserineeplivanserine may increase the anticoagulant activities of Urokinase.Investigational
EpoprostenolEpoprostenol may increase the anticoagulant activities of Urokinase.Approved
EptifibatideEptifibatide may increase the anticoagulant activities of Urokinase.Approved, Investigational
Ethyl biscoumacetateUrokinase may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
Ferulic acidUrokinase may increase the anticoagulant activities of Ferulic acid.Experimental
FluindioneUrokinase may increase the anticoagulant activities of Fluindione.Investigational
FondaparinuxUrokinase may increase the anticoagulant activities of Fondaparinux.Investigational
Fondaparinux sodiumUrokinase may increase the anticoagulant activities of Fondaparinux sodium.Approved, Investigational
GabexateUrokinase may increase the anticoagulant activities of Gabexate.Investigational
GuacetisalThe risk or severity of adverse effects can be increased when Guacetisal is combined with Urokinase.Experimental
Hemoglobin crosfumarilThe risk or severity of adverse effects can be increased when Hemoglobin crosfumaril is combined with Urokinase.Experimental
HeparinUrokinase may increase the anticoagulant activities of Heparin.Approved, Investigational
HydroxytyrosolHydroxytyrosol may increase the anticoagulant activities of Urokinase.Investigational
IbudilastIbudilast may increase the anticoagulant activities of Urokinase.Approved, Investigational
Icosapent ethylIcosapent ethyl may increase the anticoagulant activities of Urokinase.Approved, Nutraceutical
IdraparinuxUrokinase may increase the anticoagulant activities of Idraparinux.Investigational
IfenprodilIfenprodil may increase the anticoagulant activities of Urokinase.Approved, Withdrawn
IfetrobanIfetroban may increase the anticoagulant activities of Urokinase.Investigational
IloprostIloprost may increase the anticoagulant activities of Urokinase.Approved, Investigational
IndobufenIndobufen may increase the anticoagulant activities of Urokinase.Investigational
KetanserinKetanserin may increase the anticoagulant activities of Urokinase.Investigational
LepirudinUrokinase may increase the anticoagulant activities of Lepirudin.Approved
LetaxabanUrokinase may increase the anticoagulant activities of Letaxaban.Investigational
LimaprostThe risk or severity of adverse effects can be increased when Limaprost is combined with Urokinase.Approved
LinsidomineLinsidomine may increase the anticoagulant activities of Urokinase.Experimental
MelagatranUrokinase may increase the anticoagulant activities of Melagatran.Experimental
MesalazineThe risk or severity of adverse effects can be increased when Mesalazine is combined with Urokinase.Approved
MilrinoneMilrinone may increase the anticoagulant activities of Urokinase.Approved
NadroparinUrokinase may increase the anticoagulant activities of Nadroparin.Approved
NafamostatUrokinase may increase the anticoagulant activities of Nafamostat.Approved, Investigational
NaftopidilNaftopidil may increase the anticoagulant activities of Urokinase.Investigational
NimesulideNimesulide may increase the anticoagulant activities of Urokinase.Approved, Withdrawn
NitroaspirinNitroaspirin may increase the anticoagulant activities of Urokinase.Investigational
OlsalazineThe risk or severity of adverse effects can be increased when Olsalazine is combined with Urokinase.Approved
OtamixabanUrokinase may increase the anticoagulant activities of Otamixaban.Investigational
Pentosan PolysulfateUrokinase may increase the anticoagulant activities of Pentosan Polysulfate.Approved
PentoxifyllinePentoxifylline may increase the anticoagulant activities of Urokinase.Approved, Investigational
PhenindioneUrokinase may increase the anticoagulant activities of Phenindione.Approved
PhenprocoumonUrokinase may increase the anticoagulant activities of Phenprocoumon.Approved
PicotamidePicotamide may increase the anticoagulant activities of Urokinase.Experimental
PrasugrelPrasugrel may increase the anticoagulant activities of Urokinase.Approved
Protein CUrokinase may increase the anticoagulant activities of Protein C.Approved
Protein S humanUrokinase may increase the anticoagulant activities of Protein S human.Approved
ProtocatechualdehydeUrokinase may increase the anticoagulant activities of Protocatechualdehyde.Approved
RamatrobanRamatroban may increase the anticoagulant activities of Urokinase.Investigational
ResveratrolResveratrol may increase the anticoagulant activities of Urokinase.Experimental, Investigational
ReviparinUrokinase may increase the anticoagulant activities of Reviparin.Approved
RidogrelRidogrel may increase the anticoagulant activities of Urokinase.Approved
RivaroxabanUrokinase may increase the anticoagulant activities of Rivaroxaban.Approved
Salicylic acidThe risk or severity of adverse effects can be increased when Salicylic acid is combined with Urokinase.Approved, Vet Approved
SarpogrelateSarpogrelate may increase the anticoagulant activities of Urokinase.Investigational
SevofluraneSevoflurane may increase the anticoagulant activities of Urokinase.Approved, Vet Approved
SRT501SRT501 may increase the anticoagulant activities of Urokinase.Investigational
SulodexideUrokinase may increase the anticoagulant activities of Sulodexide.Approved, Investigational
TesmilifeneTesmilifene may increase the anticoagulant activities of Urokinase.Investigational
TiclopidineTiclopidine may increase the anticoagulant activities of Urokinase.Approved
TirofibanTirofiban may increase the anticoagulant activities of Urokinase.Approved
TranilastTranilast may increase the anticoagulant activities of Urokinase.Approved, Investigational
TrapidilTrapidil may increase the anticoagulant activities of Urokinase.Approved
TreprostinilThe risk or severity of adverse effects can be increased when Urokinase is combined with Treprostinil.Approved, Investigational
TriflusalTriflusal may increase the anticoagulant activities of Urokinase.Approved
TroxerutinUrokinase may increase the anticoagulant activities of Troxerutin.Investigational
VorapaxarVorapaxar may increase the anticoagulant activities of Urokinase.Approved
WarfarinUrokinase may increase the anticoagulant activities of Warfarin.Approved
XimelagatranUrokinase may increase the anticoagulant activities of Ximelagatran.Approved, Investigational, Withdrawn
Food Interactions
Not Available

References

Synthesis Reference

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

US4258030
General References
  1. Housley C: Contract purchasing means a buyer's market. Dimens Health Serv. 1976 Apr;53(4):16, 19-20. [PubMed:5328]
External Links
UniProt
P00749
Genbank
X02419
ChEMBL
CHEMBL1201420
Therapeutic Targets Database
DAP001194
PharmGKB
PA451836
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Urokinase
ATC Codes
B01AD04 — Urokinase
AHFS Codes
  • 20:12.20
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Not Yet RecruitingTreatmentHeavy Menstrual Bleeding1
2CompletedTreatmentAcute Peripheral Arterial Occlusion1
2CompletedTreatmentArterial Occlusive Diseases / Diabetic Foot / Transient ischemia attacks1
2, 3TerminatedTreatmentSinus Thrombosis, Intracranial1
2, 3Unknown StatusTreatmentPleural Empyema1
3CompletedTreatmentEmpyema / Pneumonia1
3CompletedTreatmentUterine Bleeding in Women With Leiomyomas1
3RecruitingTreatmentPleural Empyema1
3TerminatedTreatmentArterial Occlusive Diseases / Diabetic Foot / Transient ischemia attacks1
3TerminatedTreatmentCritical Limb Ischemia (CLI) / Diabetic Foot1
3Unknown StatusTreatmentRetained Hemothorax1
3WithdrawnTreatmentLeiomyomas1
4CompletedTreatmentProphylaxis of Pulmonary embolism / Pulmonary Thromboembolisms1
4CompletedTreatmentProphylaxis of Pulmonary embolism / Thromboembolism1
4Not Yet RecruitingTreatmentCoronary Artery Disease1
4RecruitingBasic ScienceContraception1
Not AvailableEnrolling by InvitationTreatmentThrombosis, Venous1
Not AvailableNot Yet RecruitingNot AvailableStroke, Ischemic1
Not AvailableUnknown StatusNot AvailableInfertilities1

Pharmacoeconomics

Manufacturers
  • Microbix biosystems inc
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous250000 unit
Powder, for solutionIntravenous5000 unit
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)76 °C at pH 4.5Nowak, U.K. et al., Biochemistry 33:2951-2960 (1994)
hydrophobicity-0.466Not Available
isoelectric point8.66Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Activator
General Function
Serine-type peptidase activity
Specific Function
Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In...
Gene Name
PLG
Uniprot ID
P00747
Uniprot Name
Plasminogen
Molecular Weight
90568.415 Da
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:12658774]
  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:12666133]
  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:12719778]
  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:12720300]
  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:12745435]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Urokinase plasminogen activator receptor activity
Specific Function
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-...
Gene Name
PLAUR
Uniprot ID
Q03405
Uniprot Name
Urokinase plasminogen activator surface receptor
Molecular Weight
36977.62 Da
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:12615913]
  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:12817472]
  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:14679304]
  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:14688365]
  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:14720519]
  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:17327908]
Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Serine-type endopeptidase activity
Specific Function
Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
Gene Name
PLAU
Uniprot ID
P00749
Uniprot Name
Urokinase-type plasminogen activator
Molecular Weight
48507.09 Da
References
  1. Bell WR: Present-day thrombolytic therapy: therapeutic agents--pharmacokinetics and pharmacodynamics. Rev Cardiovasc Med. 2002;3 Suppl 2:S34-44. [PubMed:12556741]
  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:12579271]
  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:12707394]
  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:12745435]
  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:12824001]
Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Serine-type endopeptidase activity
Specific Function
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 t...
Gene Name
PLAT
Uniprot ID
P00750
Uniprot Name
Tissue-type plasminogen activator
Molecular Weight
62916.495 Da
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:12745435]
  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:12787697]
  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:12826021]
  4. Wells RG, Havens PL: Intrapleural fibrinolysis for parapneumonic effusion and empyema in children. Radiology. 2003 Aug;228(2):370-8. [PubMed:12893898]
  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:14507109]
Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Serine protease inhibitor. This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, protein C and matriptase-3/TMPRSS7. Its rapid interaction with PLAT may function as a major con...
Gene Name
SERPINE1
Uniprot ID
P05121
Uniprot Name
Plasminogen activator inhibitor 1
Molecular Weight
45059.695 Da
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:12579271]
  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:12642587]
  3. Hellgren M: Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost. 2003 Apr;29(2):125-30. [PubMed:12709915]
  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:12745435]
  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:12785198]
Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Inhibits urokinase-type plasminogen activator. The monocyte derived PAI-2 is distinct from the endothelial cell-derived PAI-1.
Gene Name
SERPINB2
Uniprot ID
P05120
Uniprot Name
Plasminogen activator inhibitor 2
Molecular Weight
46595.84 Da
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:15277569]
  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:15351849]
  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:15640330]
  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:15944795]
  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:16327990]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of...
Gene Name
SERPINA5
Uniprot ID
P05154
Uniprot Name
Plasma serine protease inhibitor
Molecular Weight
45674.315 Da
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(4 Suppl):1049-57. Epub 2007 Apr 16. [PubMed:17434507]
  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:17253188]
  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:14645112]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Calcium ion binding
Specific Function
Acts together with cubilin to mediate HDL endocytosis (By similarity). May participate in regulation of parathyroid-hormone and para-thyroid-hormone-related protein release.
Gene Name
LRP2
Uniprot ID
P98164
Uniprot Name
Low-density lipoprotein receptor-related protein 2
Molecular Weight
521952.77 Da
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:17139284]
  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:17016423]
  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:8241286]
  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:1280065]
  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:7959795]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type peptidase activity
Specific Function
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...
Gene Name
ST14
Uniprot ID
Q9Y5Y6
Uniprot Name
Suppressor of tumorigenicity 14 protein
Molecular Weight
94769.01 Da
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:14747469]
  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:12815039]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Proteoglycan binding
Specific Function
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 inter...
Gene Name
NID1
Uniprot ID
P14543
Uniprot Name
Nidogen-1
Molecular Weight
136375.93 Da
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:17139284]
  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:17016423]
  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:1499567]

Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23