Reteplase

Identification

Summary

Reteplase is a purified form of human tissue plasminogen activator used in the emergency treatment of myocardial infarction, ischemic stroke, and pulmonary emboli.

Brand Names
Retavase
Generic Name
Reteplase
DrugBank Accession Number
DB00015
Background

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).

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Thrombolytic agents
Protein Structure
Db00015
Protein Chemical Formula
C1736H2671N499O522S22
Protein Average Weight
39589.6 Da
Sequences
>DB00015 sequence
SYQGNSDCYFGNGSAYRGTHSLTESGASCLPWNSMILIGKVYTAQNPSAQALGLGKHNYC
RNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCGLRQYSQPQFRIKGGLFADIASHPWQAA
IFAKHRRSPGERFLCGGILISSCWILSAAHCFQERFPPHHLTVILGRTYRVVPGEEEQKF
EVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCAQESSVVRTVCLPPADLQLPDWTECELS
GYGKHEALSPFYSERLKEAHVRLYPSSRCTSQHLLNRTVTDNMLCAGDTRSGGPQANLHD
ACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQKDVPGVYTKVTNYLDWIRDNMRP
Download FASTA Format
Synonyms
  • Human t-PA (residues 1-3 and 176-527)
  • Reteplasa
  • Reteplase
  • Reteplase, recombinant
  • Reteplase,recombinant
External IDs
  • BM 06.022
  • BM-06.022
  • BM-06022

Pharmacology

Indication

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

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
APlasminogen
activator
Humans
AFibrinogen alpha chainNot AvailableHumans
UPlasminogen activator inhibitor 1Not AvailableHumans
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

Adverse Effects
Adverseeffects
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Toxicity

Not Available

Pathways
PathwayCategory
Reteplase Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Reteplase.
AceclofenacThe risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Reteplase.
AcemetacinThe risk or severity of bleeding and hemorrhage can be increased when Reteplase is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding can be increased when Reteplase is combined with Acenocoumarol.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Reteplase.
Albutrepenonacog alfaThe therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with Reteplase.
AlclofenacThe risk or severity of bleeding and hemorrhage can be increased when Alclofenac is combined with Reteplase.
AldesleukinThe risk or severity of bleeding can be increased when Reteplase is combined with Aldesleukin.
AlemtuzumabThe risk or severity of bleeding can be increased when Reteplase is combined with Alemtuzumab.
AlogliptinThe risk or severity of angioedema can be increased when Reteplase is combined with Alogliptin.
Interactions
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Food Interactions
  • Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Products

Products2
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RapilysinInjection, powder, for solution10 UIntravenousActavis Group Ptc Ehf.2020-12-22Not applicableEU flag
RetavaseKit1.81 mg/1mLIntravenousChiesi USA, Inc.1996-10-30Not applicableUS flag
RetavaseKit1.81 mg/1mLIntravenousEkr Therapeutics1996-10-302017-07-01US flag
RetavaseKit1.81 mg/1mLIntravenousChiesi USA, Inc.1996-10-30Not applicableUS flag
RetavaseKit1.81 mg/1mLIntravenousEkr Therapeutics1996-10-302017-07-01US flag
RetavasePowder, for solution10.4 unit / vialIntravenousEkr Therapeutics1999-02-192013-08-29Canada flag

Categories

ATC Codes
B01AD07 — Reteplase
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
DQA630RIE9
CAS number
133652-38-7

References

General References
Not Available
UniProt
P00750
Genbank
L00153
PubChem Substance
46506092
RxNav
76895
ChEMBL
CHEMBL2107885
Therapeutic Targets Database
DAP001195
PharmGKB
PA164743728
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Reteplase

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAcute Myocardial Infarction (AMI)1
4CompletedTreatmentAcute Myocardial Infarction (AMI) / Cardiovascular Disease (CVD) / Myocardial Infarction1
3Not Yet RecruitingTreatmentRestoration of Function to CVADs1
3RecruitingTreatmentAcute Myocardial Infarction With ST Segment Elevation1
3RecruitingTreatmentCatheter Occlusion / Thrombotic events1
2CompletedTreatmentCerebrovascular Accident1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • EKR Therapeutics Inc.
  • Hospira Inc.
  • PDL BioPharma Inc.
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous10 U
Injection, powder, lyophilized, for solutionIntravenous
KitIntravenous1.81 mg/1mL
Powder, for solutionIntravenous10.4 unit / vial
Injection, powder, lyophilized, for solutionIntravenous18 mg
Prices
Unit descriptionCostUnit
Retavase vial half-kit2605.93USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2107476No2007-12-182012-04-15Canada flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)60 °CNovokhatny, V.V. et al., J. Biol. Chem. 266:12994-123002 (1991)
hydrophobicity-0.435Not Available
isoelectric point6.86Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
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. 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. [Article]
  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. [Article]
  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. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
General Function
Structural molecule activity
Specific Function
Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function ...
Gene Name
FGA
Uniprot ID
P02671
Uniprot Name
Fibrinogen alpha chain
Molecular Weight
94972.455 Da
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. 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. [Article]

Drug created on June 13, 2005 13:24 / Updated on October 03, 2021 00:33