Identification

Name
Streptokinase
Accession Number
DB00086  (BTD00028, BIOD00028)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Thrombolytic agents
Description

Streptokinase, is a sterile, purified preparation of a bacterial protein elaborated by group C (beta) -hemolytic streptococci.

Protein structure
Db00086
Protein chemical formula
C2100H3278N566O669S4
Protein average weight
47286.7 Da
Sequences
>Streptokinase Sequence DB00086
MKNYLSFGMFALLFALTFGTVNSVQAIAGPEWLLDRPSVNNSQLVVSVAGTVEGTNQDIS
LKFFEIDLTSRPAHGGKTEQGLSPKSKPFATDSGAMSHKLEKADLLKAIQEQLIANVHSN
DDYFEVIDFASDATITDRNGKVYFADKDGSVTLPTQPVQEFLLSGHVRVRPYKEKPIQNQ
AKSVDVEYTVQFTPLNPDDDFRPGLKDTKLLKTLAIGDTITSQELLAQAQSILNKNHPGY
TIYERDSSIVTHDNDIFRTILPMDQEFTYRVKNREQAYRINKKSGLNEEINNTDLISEKY
YVLKKGEKPYDPFDRSHLKLFTIKYVDVDTNELLKSEQLLTASERNLDFRDLYDPRDKAK
LLYNNLDAFGIMDYTLTGKVEDNHDDTNRIITVYMGKRPEGENASYHLAYDKDRYTEEER
EVYSYLRYTGTPIPDNPNDK
Download FASTA Format
Synonyms
  • Streptokinase C precursor
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Kabikinase - Pws 1500000units/vialPowder, for solution1500000 unitIntracoronary; IntravenousPharmacia & Upjohn Inc1995-12-312001-07-30Canada
Kabikinase - Pws 250000 Unit/vialPowder, for solution250000 unitIntracoronary; IntravenousPharmacia & Upjohn Inc1995-12-311999-08-12Canada
Kabikinase - Pws 750000units/vialPowder, for solution750000 unitIntracoronary; IntravenousPharmacia & Upjohn Inc1995-12-312001-07-30Canada
StreptasePowder, for solution1500000 unitIntracoronary; IntravenousCsl Behring1994-12-312012-02-22Canada
StreptasePowder, for solution750000 unitIntracoronary; IntravenousCsl Behring1994-12-312012-02-22Canada
StreptasePowder, for solution250000 unitIntracoronary; IntravenousCsl Behring1994-12-312012-02-22Canada
Streptase Inj 1500000 Unit/vialPowder, for solution1500000 unitIntravenousHoechst Canada Inc.1991-12-311996-08-29Canada
Streptase Inj 250000unit/vialPowder, for solution250000 unitIntravenousHoechst Canada Inc.1981-12-311996-08-29Canada
Streptase Inj 750000unit/vialPowder, for solution750000 unitIntravenousHoechst Canada Inc.1981-12-311996-08-29Canada
Categories
UNII
8X1OXL3SNU
CAS number
9002-01-1

Pharmacology

Indication

For the treatment of acute evolving transmural myocardial infarction, pulmonary embolism, deep vein thrombosis, arterial thrombosis or emolism and occlusion of arteriovenous cannulae

Pharmacodynamics

Streptokinase creates an active complex which promotes the cleavage of the Arg/Val bond in plasminogen to form the proteolytic enzyme plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action. This helps eliminate blood clots or arterial blockages that cause myocardial infarction.

Mechanism of action

Plasminogen is an inactive molecule that becomes activated to plasmin when the Arg/Val bond is cleaved. Plasmin breaks down fibrin clots created by the blood clotting cascade. Streptokinase forms a highly specific 1:1 enzymatic complex with plasminogen which converts inactive plasminogen molecules into active plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. This in turn leads to the degradation of blood clots.

TargetActionsOrganism
APlasminogen
activator
Human
UProteinase-activated receptor 1
cleavage
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Streptokinase Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1,2,6,7-3H)TestosteroneThe therapeutic efficacy of Streptokinase can be increased when used in combination with (1,2,6,7-3H)Testosterone.
(R)-warfarinThe risk or severity of bleeding can be increased when Streptokinase is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Streptokinase is combined with (S)-Warfarin.
1-TestosteroneThe therapeutic efficacy of Streptokinase can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Streptokinase can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Streptokinase is combined with 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Streptokinase can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Streptokinase can be increased when used in combination with 5beta-dihydrotestosterone.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Streptokinase.
AcebutololThe risk or severity of adverse effects can be increased when Streptokinase is combined with Acebutolol.
Food Interactions
Not Available

References

Synthesis Reference

Lawrence Isaac Galler, "Streptokinase derivatives with high affinity for activated platelets and methods of their production and use in thrombolytic therapy." U.S. Patent US6087332, issued July, 1997.

US6087332
General References
Not Available
External Links
UniProt
P00779
Genbank
K02986
PubChem Substance
46505625
ChEMBL
CHEMBL2108147
Therapeutic Targets Database
DAP001198
PharmGKB
PA164754919
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Streptokinase
ATC Codes
B01AD01 — StreptokinaseB06AA55 — Streptokinase, combinations

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Unknown StatusTreatmentStroke, Ischemic1
2, 3CompletedTreatmentAcute Pancreatitis (AP)1
3CompletedTreatmentAcute Myocardial Infarction (AMI)1
3CompletedTreatmentAcute Respiratory Distress Syndrome (ARDS) / Severe Acute Respiratory Syndrome1
3CompletedTreatmentCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Heart Diseases / Myocardial Infarction / Myocardial Ischemia2
3CompletedTreatmentMyocardial Infarction1
3CompletedTreatmentProsthetic Valve Thrombosis1
4CompletedTreatmentAcute Coronary Syndromes (ACS) / Acute Myocardial Infarction (AMI) / Reperfusion Injury1
4CompletedTreatmentAcute Myocardial Infarction (AMI)1
4Not Yet RecruitingTreatmentPleural Effusions1
Not AvailableCompletedTreatmentProsthetic Valve Thrombosis1
Not AvailableNot Yet RecruitingTreatmentPulmonary Embolism (PE)1
Not AvailableRecruitingDiagnosticMyocardial Infarction / Myocardial Injury / Myocardial Necrosis / ST Elevation Myocardial Infarction (STEMI)1
Not AvailableWithdrawnNot AvailableAcute Coronary Syndromes (ACS) / Non ST Elevation Myocardial Infarction / ST Elevation Myocardial Infarction / Unstable Angina (UA)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Pfizer Inc.
Dosage forms
FormRouteStrength
Powder, for solutionIntracoronary; Intravenous1500000 unit
Powder, for solutionIntracoronary; Intravenous250000 unit
Powder, for solutionIntracoronary; Intravenous750000 unit
Powder, for solutionIntravenous1500000 unit
Powder, for solutionIntravenous250000 unit
Powder, for solutionIntravenous750000 unit
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.728Not Available
isoelectric point5.12Not 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. Caballero AR, Lottenberg R, Johnston KH: Cloning, expression, sequence analysis, and characterization of streptokinases secreted by porcine and equine isolates of Streptococcus equisimilis. Infect Immun. 1999 Dec;67(12):6478-86. [PubMed:10569766]
  2. Alessi MC, Juhan-Vague I: [Thrombolytics and their use]. Rev Prat. 1999 Oct 1;49(15):1654-8. [PubMed:10581996]
  3. Chaudhary A, Vasudha S, Rajagopal K, Komath SS, Garg N, Yadav M, Mande SC, Sahni G: Function of the central domain of streptokinase in substrate plasminogen docking and processing revealed by site-directed mutagenesis. Protein Sci. 1999 Dec;8(12):2791-805. [PubMed:10631997]
  4. Parry MA, Zhang XC, Bode I: Molecular mechanisms of plasminogen activation: bacterial cofactors provide clues. Trends Biochem Sci. 2000 Feb;25(2):53-9. [PubMed:10664583]
  5. Korol'chuk VI, Makohonenko IeM, Sederkhol'm-Vil'iams SA: [Plasminogen binding with decapeptide and polypeptide fragments of streptokinase]. Ukr Biokhim Zh (1999). 1999 Sep-Oct;71(5):51-8. [PubMed:10726310]
  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
Unknown
Actions
Cleavage
General Function
Thrombin receptor activity
Specific Function
High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation and in vascular development.
Gene Name
F2R
Uniprot ID
P25116
Uniprot Name
Proteinase-activated receptor 1
Molecular Weight
47439.83 Da
References
  1. McRedmond JP, Harriott P, Walker B, Fitzgerald DJ: Streptokinase-induced platelet activation involves antistreptokinase antibodies and cleavage of protease-activated receptor-1. Blood. 2000 Feb 15;95(4):1301-8. [PubMed:10666203]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Phospholipase a2 activity
Specific Function
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory...
Gene Name
PLA2G4A
Uniprot ID
P47712
Uniprot Name
Cytosolic phospholipase A2
Molecular Weight
85238.2 Da
References
  1. Kawaguchi H, Iizuka K, Sano H, Yasuda H: Effect of streptokinase on prostacyclin synthesis and phospholipase activity in cultured pulmonary artery endothelial cells. Biochim Biophys Acta. 1990 Dec 10;1055(3):223-9. [PubMed:2265209]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2018 19:13