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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 Db00015
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
Salts Not Available
Brand names
Name Company
Retavase (Centocor)
Retavase (Roche)
Brand 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
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
Smp00285 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
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
Canada 2107476 2007-12-18 2012-04-15
Properties
State liquid
Experimental Properties
Property Value Source
melting point 60 °C Novokhatny, V.V. et al., J. Biol. Chem. 266:12994-123002 (1991)
hydrophobicity -0.435 Not Available
isoelectric point 6.86 Not Available
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
UniProt P00750 Link_out
Genbank L00153 Link_out
PharmGKB PA164743728 Link_out
Drug Product Database 2233013 Link_out
RxList http://www.rxlist.com/cgi/generic2/reteplase.htm Link_out
Drugs.com http://www.drugs.com/cdi/reteplase.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Reteplase Link_out
ATC Codes
  • B01AD07
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
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 Link_out
Gene: PLG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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:
  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

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:
  1. 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