DrugBank: Streptokinase (DB00086)

targets (2) enzymes (1)

Identification

Name

Streptokinase

Accession Number

DB00086 (BIOD00028, BTD00028)

Type

biotech

Groups

approved

Description

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

Protein structure

Display: 3D Structure

Protein chemical formula

C₂₁₀₀H₃₂₇₈N₅₆₆O₆₆₉S₄

Protein average weight

47286.7000

Sequences

>DB00086 sequence
IAGPEWLLDRPSVNNSQLVVSVAGTVEGTNQDISLKFFEIDLTSRPAHGGKTEQGLSPKS
KPFATDSGAMSHKLEKADLLKAIQEQLIANVHSNDDYFEVIDFASDATITDRNGKVYFAD
KDGSVTLPTQPVQEFLLSGHVRVRPYKEKPIQNQAKSVDVEYTVQFTPLNPDDDFRPGLK
DTKLLKTLAIGDTITSQELLAQAQSILNKNHPGYTIYERDSSIVTHDNDIFRTILPMDQE
FTYRVKNREQAYRINKKSGLNEEINNTDLISEKYYVLKKGEKPYDPFDRSHLKLFTIKYV
DVDTNELLKSEQLLTASERNLDFRDLYDPRDKAKLLYNNLDAFGIMDYTLTGKVEDNHDD
TNRIITVYMGKRPEGENASYHLAYDKDRYTEEEREVYSYLRYTGTPIPDNPNDK

FASTA

Synonyms

Streptokinase C precursor

Salts

Not Available

Brand names

Name	Company
Streptase (Aventis Behringer GmbH)

Brand mixtures

Not Available

Categories

Thrombolytic Agents

CAS number

9002-01-1

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

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.

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

Pathway	Name	SMPDB ID
	Streptokinase Pathway	SMP00282

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Pfizer Inc.

Dosage forms

Form	Route	Strength
Powder, for solution	Intravenous

Prices

Not Available

Patents

Not Available

Properties

State

liquid

Experimental Properties

Property	Value	Source
hydrophobicity	-0.728	Not Available
isoelectric point	5.12	Not Available

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
UniProt	P00779
Genbank	K02986
PharmGKB	PA164754919
Drug Product Database	2018993
RxList	http://www.rxlist.com/cgi/generic2/streptokinase.htm
Drugs.com	http://www.drugs.com/cons/streptokinase-intravenous-intracoronary.html
Wikipedia	http://en.wikipedia.org/wiki/Streptokinase

ATC Codes

B01AD01
B06AA55

AHFS Codes

20:12.20

PDB Entries

1BML

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Drug	Interaction
Ticlopidine	Increased bleeding risk. Monitor for signs 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 Gene: PLG Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Alessi MC, Juhan-Vague I: [Thrombolytics and their use] Rev Prat. 1999 Oct 1;49(15):1654-8. Pubmed 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 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 Korol’chuk VI, Makohonenko IeM, Sederkhol’m-Vil’iams SA: [Plasminogen binding with decapeptide and polypeptide fragments of streptokinase] Ukr Biokhim Zh. 1999 Sep-Oct;71(5):51-8. Pubmed Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed 2. Proteinase-activated receptor 1 Pharmacological action: unknown Actions: cleavage 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 Organism class: human UniProt ID: P25116 Gene: F2R Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

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

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
Alessi MC, Juhan-Vague I: [Thrombolytics and their use] Rev Prat. 1999 Oct 1;49(15):1654-8. Pubmed
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
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
Korol’chuk VI, Makohonenko IeM, Sederkhol’m-Vil’iams SA: [Plasminogen binding with decapeptide and polypeptide fragments of streptokinase] Ukr Biokhim Zh. 1999 Sep-Oct;71(5):51-8. Pubmed
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Proteinase-activated receptor 1

Pharmacological action: unknown
Actions: cleavage

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

Organism class: human
UniProt ID: P25116 Link_out

Gene: F2R

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Enzymes
1. Cytosolic phospholipase A2 Actions: inducer 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 response UniProt ID: P47712 Gene: PLA2G4A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Enzymes

1. Cytosolic phospholipase A2

Actions: inducer

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 response

UniProt ID: P47712 Link_out

Gene: PLA2G4A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Comments

Drug created on June 13, 2005 07:24 / Updated on July 27, 2012 01:15