DrugBank: Reteplase (DB00015)

targets (4)

Identification

Name

Reteplase

Accession Number

DB00015 (BIOD00013, BTD00013)

Type

biotech

Groups

approved

Description

Human tissue plasminogen activator, purified, glycosylated, 355 residues purified from CHO cells. Retavase is considered a “third-generation” thrombolytic agent, genetically engineered to retain and delete certain portions of human tPA. Retavase is a deletion mutein of human tPA formed by deleting various amino acids present in endogenous human tPA. Retavase contains 355 of the 527 amino acids of native human tPA (amino acids 1-3 and 176-527), and retains the activity-related kringle-2 and serine protease domains of human tPA. Three domains are deleted from retavase – kringle-1, finger, and epidermal growth factor (EGF).

Protein structure

Display: 3D Structure

Protein chemical formula

C₁₇₃₆H₂₆₇₁N₄₉₉O₅₂₂S₂₂

Protein average weight

39589.6000

Sequences

>DB00015 sequence
SYQGNSDCYFGNGSAYRGTHSLTESGASCLPWNSMILIGKVYTAQNPSAQALGLGKHNYC
RNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCGLRQYSQPQFRIKGGLFADIASHPWQAA
IFAKHRRSPGERFLCGGILISSCWILSAAHCFQERFPPHHLTVILGRTYRVVPGEEEQKF
EVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCAQESSVVRTVCLPPADLQLPDWTECELS
GYGKHEALSPFYSERLKEAHVRLYPSSRCTSQHLLNRTVTDNMLCAGDTRSGGPQANLHD
ACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQKDVPGVYTKVTNYLDWIRDNMRP

FASTA

Synonyms

t- PA
t-plasminogen activator
Tissue-type plasminogen activator precursor
tPA

Brand names

Retavase (Centocor)
Retavase (Roche)

Brand name mixtures

Not Available

Categories

Thrombolytic Agents

CAS number

133652-38-7

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

For lysis of acute pulmonary emboli, intracoronary emboli and management of myocardial infarction

Pharmacodynamics

Reteplase cleaves the Arg/Val bond in plasminogen to form 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

Reteplase binds to fibrin rich clots via the fibronectin finger-like domain and the Kringle 2 domain. The protease domain then cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

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
	Reteplase Pathway	SMP00285

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Dosage forms

Form	Route	Strength
Injection, powder, lyophilized, for solution	Intravenous bolus

Prices

Unit description	Cost	Unit
Retavase vial half-kit	2605.93 USD	vial

Patents

Country	Patent Number	Approved	Expires
Canada	2107476	2007-12-18	2012-04-15

Properties

State

liquid

Melting point

60 oC (Novokhatny, V.V. et al., J. Biol. Chem. 266:12994-123002 (1991))

Experimental Properties

Property	Value	Source
hydrophobicity	-0.435	PhysProp
isoelectric point	6.86	Various sources

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
UniProt	P00750
Genbank	L00153
Drug Product Database	2233013
RxList	http://www.rxlist.com/cgi/generic2/reteplase.htm
Drugs.com	http://www.drugs.com/cdi/reteplase.html
Wikipedia	http://en.wikipedia.org/wiki/Reteplase

ATC Codes

B01AD07

AHFS Codes

Not Available

PDB Entries

1BDA

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

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: Hilleman DE, Tsikouris JP, Seals AA, Marmur JD: Fibrinolytic agents for the management of ST-segment elevation myocardial infarction. Pharmacotherapy. 2007 Nov;27(11):1558-70. Pubmed Longstaff C, Williams S, Thelwell C: Fibrin binding and the regulation of plasminogen activators during thrombolytic therapy. Cardiovasc Hematol Agents Med Chem. 2008 Jul;6(3):212-23. Pubmed Melandri G, Vagnarelli F, Calabrese D, Semprini F, Nanni S, Branzi A: Review of tenecteplase (TNKase) in the treatment of acute myocardial infarction. Vasc Health Risk Manag. 2009;5(1):249-56. Epub 2009 Apr 8. Pubmed Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed 2. Fibrinogen alpha chain Pharmacological action: yes Fibrinogen has a double function:yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation Organism class: human UniProt ID: P02671 Gene: FGA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Longstaff C, Williams S, Thelwell C: Fibrin binding and the regulation of plasminogen activators during thrombolytic therapy. Cardiovasc Hematol Agents Med Chem. 2008 Jul;6(3):212-23. Pubmed Melandri G, Vagnarelli F, Calabrese D, Semprini F, Nanni S, Branzi A: Review of tenecteplase (TNKase) in the treatment of acute myocardial infarction. Vasc Health Risk Manag. 2009;5(1):249-56. Epub 2009 Apr 8. Pubmed Hilleman DE, Tsikouris JP, Seals AA, Marmur JD: Fibrinolytic agents for the management of ST-segment elevation myocardial infarction. Pharmacotherapy. 2007 Nov;27(11):1558-70. Pubmed 3. Urokinase plasminogen activator surface receptor Pharmacological action: unknown 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 Gene: PLAUR Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 4. Plasminogen activator inhibitor 1 Pharmacological action: unknown 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 Gene: SERPINE1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Hilleman DE, Tsikouris JP, Seals AA, Marmur JD: Fibrinolytic agents for the management of ST-segment elevation myocardial infarction. Pharmacotherapy. 2007 Nov;27(11):1558-70. 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:

Hilleman DE, Tsikouris JP, Seals AA, Marmur JD: Fibrinolytic agents for the management of ST-segment elevation myocardial infarction. Pharmacotherapy. 2007 Nov;27(11):1558-70. Pubmed
Longstaff C, Williams S, Thelwell C: Fibrin binding and the regulation of plasminogen activators during thrombolytic therapy. Cardiovasc Hematol Agents Med Chem. 2008 Jul;6(3):212-23. Pubmed
Melandri G, Vagnarelli F, Calabrese D, Semprini F, Nanni S, Branzi A: Review of tenecteplase (TNKase) in the treatment of acute myocardial infarction. Vasc Health Risk Manag. 2009;5(1):249-56. Epub 2009 Apr 8. Pubmed
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Fibrinogen alpha chain

Pharmacological action: yes

Fibrinogen has a double function:yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation

Organism class: human
UniProt ID: P02671 Link_out

Gene: FGA

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

References:

Longstaff C, Williams S, Thelwell C: Fibrin binding and the regulation of plasminogen activators during thrombolytic therapy. Cardiovasc Hematol Agents Med Chem. 2008 Jul;6(3):212-23. Pubmed
Melandri G, Vagnarelli F, Calabrese D, Semprini F, Nanni S, Branzi A: Review of tenecteplase (TNKase) in the treatment of acute myocardial infarction. Vasc Health Risk Manag. 2009;5(1):249-56. Epub 2009 Apr 8. Pubmed
Hilleman DE, Tsikouris JP, Seals AA, Marmur JD: Fibrinolytic agents for the management of ST-segment elevation myocardial infarction. Pharmacotherapy. 2007 Nov;27(11):1558-70. Pubmed

3. Urokinase plasminogen activator surface receptor

Pharmacological action: unknown

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:

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

4. Plasminogen activator inhibitor 1

Pharmacological action: unknown

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:

Hilleman DE, Tsikouris JP, Seals AA, Marmur JD: Fibrinolytic agents for the management of ST-segment elevation myocardial infarction. Pharmacotherapy. 2007 Nov;27(11):1558-70. Pubmed

Comments

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

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.