Identification

Name
Reteplase
Accession Number
DB00015  (BTD00013, BIOD00013)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Thrombolytic agents
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
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)
  • Reteplase, recombinant
  • Reteplase,recombinant
External IDs
BM 06.022 / BM-06.022 / BM-06022
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RetavaseKitEkr Therapeutics1996-10-302017-03-14Us
RetavasePowder, for solution10.4 unitIntravenousEkr Therapeutics1999-02-192013-08-29Canada
RetavaseKitChiesi Pharmaceuticals Inc.1996-10-30Not applicableUs
RetavaseKitEkr Therapeutics1996-10-302017-03-14Us
RetavaseKitChiesi Pharmaceuticals Inc.1996-10-30Not applicableUs
Categories
UNII
DQA630RIE9
CAS number
133652-38-7

Pharmacology

Indication

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

Structured Indications
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
Human
AFibrinogen alpha chainNot AvailableHuman
UUrokinase plasminogen activator surface receptorNot AvailableHuman
UPlasminogen activator inhibitor 1Not AvailableHuman
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
Reteplase Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbciximabReteplase may increase the anticoagulant activities of Abciximab.Approved
AcenocoumarolReteplase may increase the anticoagulant activities of Acenocoumarol.Approved
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Reteplase.Approved, Vet Approved
AloxiprinThe risk or severity of adverse effects can be increased when Aloxiprin is combined with Reteplase.Experimental
AlprostadilAlprostadil may increase the anticoagulant activities of Reteplase.Approved, Investigational
Aminosalicylic AcidThe risk or severity of adverse effects can be increased when Aminosalicylic Acid is combined with Reteplase.Approved
AnagrelideAnagrelide may increase the anticoagulant activities of Reteplase.Approved
AncrodReteplase may increase the anticoagulant activities of Ancrod.Investigational
AndrographolideAndrographolide may increase the anticoagulant activities of Reteplase.Investigational
Antithrombin III humanReteplase may increase the anticoagulant activities of Antithrombin III human.Approved
ApixabanReteplase may increase the anticoagulant activities of Apixaban.Approved
AprotininThe therapeutic efficacy of Reteplase can be decreased when used in combination with Aprotinin.Approved, Withdrawn
ArdeparinReteplase may increase the anticoagulant activities of Ardeparin.Approved, Investigational, Withdrawn
ArgatrobanReteplase may increase the anticoagulant activities of Argatroban.Approved, Investigational
AzelastineAzelastine may increase the anticoagulant activities of Reteplase.Approved
BalsalazideThe risk or severity of adverse effects can be increased when Balsalazide is combined with Reteplase.Approved, Investigational
BecaplerminReteplase may increase the anticoagulant activities of Becaplermin.Approved, Investigational
BeraprostBeraprost may increase the anticoagulant activities of Reteplase.Investigational
BivalirudinReteplase may increase the anticoagulant activities of Bivalirudin.Approved, Investigational
BuflomedilBuflomedil may increase the anticoagulant activities of Reteplase.Experimental
ButylphthalideButylphthalide may increase the anticoagulant activities of Reteplase.Investigational
CangrelorCangrelor may increase the anticoagulant activities of Reteplase.Approved
CertoparinReteplase may increase the anticoagulant activities of Certoparin.Approved, Investigational
CilostazolCilostazol may increase the anticoagulant activities of Reteplase.Approved
Citric AcidReteplase may increase the anticoagulant activities of Citric Acid.Approved, Nutraceutical, Vet Approved
ClopidogrelClopidogrel may increase the anticoagulant activities of Reteplase.Approved, Nutraceutical
CloricromenCloricromen may increase the anticoagulant activities of Reteplase.Experimental
Dabigatran etexilateReteplase may increase the anticoagulant activities of Dabigatran etexilate.Approved
DalteparinReteplase may increase the anticoagulant activities of Dalteparin.Approved
DanaparoidReteplase may increase the anticoagulant activities of Danaparoid.Approved, Withdrawn
DarexabanReteplase may increase the anticoagulant activities of Darexaban.Investigational
DefibrotideDefibrotide may increase the anticoagulant activities of Reteplase.Approved, Investigational
dersalazineThe risk or severity of adverse effects can be increased when dersalazine is combined with Reteplase.Investigational
DesirudinReteplase may increase the anticoagulant activities of Desirudin.Approved
DextranReteplase may increase the anticoagulant activities of Dextran.Approved, Vet Approved
Dextran 40Reteplase may increase the anticoagulant activities of Dextran 40.Approved
Dextran 70Reteplase may increase the anticoagulant activities of Dextran 70.Approved
Dextran 75Reteplase may increase the anticoagulant activities of Dextran 75.Approved
DicoumarolReteplase may increase the anticoagulant activities of Dicoumarol.Approved
DiflunisalThe risk or severity of adverse effects can be increased when Diflunisal is combined with Reteplase.Approved
DipyridamoleDipyridamole may increase the anticoagulant activities of Reteplase.Approved
Edetic AcidReteplase may increase the anticoagulant activities of Edetic Acid.Approved, Vet Approved
EdoxabanReteplase may increase the anticoagulant activities of Edoxaban.Approved
EnoxaparinReteplase may increase the anticoagulant activities of Enoxaparin.Approved
EpinastineEpinastine may increase the anticoagulant activities of Reteplase.Approved, Investigational
EplivanserinEplivanserin may increase the anticoagulant activities of Reteplase.Investigational
eplivanserineeplivanserine may increase the anticoagulant activities of Reteplase.Investigational
EpoprostenolEpoprostenol may increase the anticoagulant activities of Reteplase.Approved
EptifibatideEptifibatide may increase the anticoagulant activities of Reteplase.Approved, Investigational
Ethyl biscoumacetateReteplase may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
Ferulic acidReteplase may increase the anticoagulant activities of Ferulic acid.Experimental
FluindioneReteplase may increase the anticoagulant activities of Fluindione.Investigational
FondaparinuxReteplase may increase the anticoagulant activities of Fondaparinux.Investigational
Fondaparinux sodiumReteplase may increase the anticoagulant activities of Fondaparinux sodium.Approved, Investigational
GabexateReteplase may increase the anticoagulant activities of Gabexate.Investigational
GuacetisalThe risk or severity of adverse effects can be increased when Guacetisal is combined with Reteplase.Experimental
Hemoglobin crosfumarilThe risk or severity of adverse effects can be increased when Hemoglobin crosfumaril is combined with Reteplase.Experimental
HeparinReteplase may increase the anticoagulant activities of Heparin.Approved, Investigational
HydroxytyrosolHydroxytyrosol may increase the anticoagulant activities of Reteplase.Investigational
IbudilastIbudilast may increase the anticoagulant activities of Reteplase.Approved, Investigational
Icosapent ethylIcosapent ethyl may increase the anticoagulant activities of Reteplase.Approved, Nutraceutical
IdraparinuxReteplase may increase the anticoagulant activities of Idraparinux.Investigational
IfenprodilIfenprodil may increase the anticoagulant activities of Reteplase.Approved, Investigational, Withdrawn
IfetrobanIfetroban may increase the anticoagulant activities of Reteplase.Investigational
IloprostIloprost may increase the anticoagulant activities of Reteplase.Approved, Investigational
IndobufenIndobufen may increase the anticoagulant activities of Reteplase.Investigational
KetanserinKetanserin may increase the anticoagulant activities of Reteplase.Investigational
LepirudinReteplase may increase the anticoagulant activities of Lepirudin.Approved
LetaxabanReteplase may increase the anticoagulant activities of Letaxaban.Investigational
LimaprostThe risk or severity of adverse effects can be increased when Limaprost is combined with Reteplase.Approved, Investigational
LinsidomineLinsidomine may increase the anticoagulant activities of Reteplase.Experimental
MelagatranReteplase may increase the anticoagulant activities of Melagatran.Experimental
MesalazineThe risk or severity of adverse effects can be increased when Mesalazine is combined with Reteplase.Approved
Methyl salicylateThe risk or severity of adverse effects can be increased when Methyl salicylate is combined with Reteplase.Approved, Vet Approved
MilrinoneMilrinone may increase the anticoagulant activities of Reteplase.Approved
NadroparinReteplase may increase the anticoagulant activities of Nadroparin.Approved
NafamostatReteplase may increase the anticoagulant activities of Nafamostat.Approved, Investigational
NaftopidilNaftopidil may increase the anticoagulant activities of Reteplase.Investigational
NimesulideNimesulide may increase the anticoagulant activities of Reteplase.Approved, Investigational, Withdrawn
NitroaspirinThe risk or severity of adverse effects can be increased when Nitroaspirin is combined with Reteplase.Investigational
OlsalazineThe risk or severity of adverse effects can be increased when Olsalazine is combined with Reteplase.Approved
OtamixabanReteplase may increase the anticoagulant activities of Otamixaban.Investigational
Pentaerythritol TetranitrateReteplase may increase the anticoagulant activities of Pentaerythritol Tetranitrate.Approved
Pentosan PolysulfateReteplase may increase the anticoagulant activities of Pentosan Polysulfate.Approved
PentoxifyllinePentoxifylline may increase the anticoagulant activities of Reteplase.Approved, Investigational
PhenindioneReteplase may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonReteplase may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
PicotamidePicotamide may increase the anticoagulant activities of Reteplase.Experimental
PrasugrelPrasugrel may increase the anticoagulant activities of Reteplase.Approved
Protein CReteplase may increase the anticoagulant activities of Protein C.Approved
Protein S humanReteplase may increase the anticoagulant activities of Protein S human.Approved
ProtocatechualdehydeReteplase may increase the anticoagulant activities of Protocatechualdehyde.Approved
RamatrobanRamatroban may increase the anticoagulant activities of Reteplase.Investigational
ResveratrolResveratrol may increase the anticoagulant activities of Reteplase.Approved, Experimental, Investigational
ReviparinReteplase may increase the anticoagulant activities of Reviparin.Approved, Investigational
RidogrelRidogrel may increase the anticoagulant activities of Reteplase.Approved
RivaroxabanReteplase may increase the anticoagulant activities of Rivaroxaban.Approved
Salicylic acidThe risk or severity of adverse effects can be increased when Salicylic acid is combined with Reteplase.Approved, Vet Approved
SarpogrelateSarpogrelate may increase the anticoagulant activities of Reteplase.Investigational
SevofluraneSevoflurane may increase the anticoagulant activities of Reteplase.Approved, Vet Approved
SRT501SRT501 may increase the anticoagulant activities of Reteplase.Investigational
SulodexideReteplase may increase the anticoagulant activities of Sulodexide.Approved, Investigational
TesmilifeneTesmilifene may increase the anticoagulant activities of Reteplase.Investigational
TicagrelorTicagrelor may increase the anticoagulant activities of Reteplase.Approved
TiclopidineTiclopidine may increase the anticoagulant activities of Reteplase.Approved
TirofibanTirofiban may increase the anticoagulant activities of Reteplase.Approved
TranilastTranilast may increase the anticoagulant activities of Reteplase.Approved, Investigational
TrapidilTrapidil may increase the anticoagulant activities of Reteplase.Approved
TreprostinilThe risk or severity of adverse effects can be increased when Reteplase is combined with Treprostinil.Approved, Investigational
TriflusalTriflusal may increase the anticoagulant activities of Reteplase.Approved, Investigational
Trolamine salicylateThe risk or severity of adverse effects can be increased when Trolamine salicylate is combined with Reteplase.Approved
TroxerutinReteplase may increase the anticoagulant activities of Troxerutin.Investigational
VorapaxarVorapaxar may increase the anticoagulant activities of Reteplase.Approved
WarfarinReteplase may increase the anticoagulant activities of Warfarin.Approved
XimelagatranReteplase may increase the anticoagulant activities of Ximelagatran.Approved, Investigational, Withdrawn
Food Interactions
Not Available

References

General References
Not Available
External Links
UniProt
P00750
Genbank
L00153
PubChem Substance
46506092
ChEMBL
CHEMBL2107885
Therapeutic Targets Database
DAP001195
PharmGKB
PA164743728
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Reteplase
ATC Codes
B01AD07 — Reteplase

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentPeritoneal dialysis therapy / Peritoneal Dialysis, Continuous Ambulatory1
1WithdrawnTreatmentStroke, Ischemic1
1, 2Unknown StatusTreatmentAcute Myelogenous Leukaemia (AML) / Myelodysplastic Syndrome1
2Active Not RecruitingTreatmentStroke, Ischemic1
2CompletedTreatmentAcute Peripheral Arterial Occlusion1
2CompletedTreatmentCerebrovascular Accidents1
2Not Yet RecruitingTreatmentPlastic Bronchitis1
2RecruitingTreatmentStroke, Ischemic1
2TerminatedTreatmentLeukemias1
2TerminatedTreatmentStrokes1
2, 3RecruitingTreatmentExudative Macular Degeneration / Retinal Hemorrhage1
2, 3TerminatedTreatmentAbscesses1
3RecruitingTreatmentPleural Empyema1
3RecruitingTreatmentStrokes2
Not AvailableCompletedTreatmentBacterial Pleural Effusion Other Than Tuberculosis / Pleural Effusion Associated With Pulmonary Infection1
Not AvailableCompletedTreatmentProsthetic Valve Thrombosis1
Not AvailableRecruitingNot AvailableStrokes1
Not AvailableRecruitingTreatmentIschemia, Brain / Strokes1
Not AvailableRecruitingTreatmentKidney Diseases1
Not AvailableTerminatedTreatmentCatheter Malfunction / Clotted Dialysis Catheter / Dialysis Catheter Fibrin Sheath1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Kit
Powder, for solutionIntravenous10.4 unit
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)
CA2107476No2007-12-182012-04-15Canada

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

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. 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:17963464]
  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:18673235]
  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:19436656]
  4. 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
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. [PubMed:18673235]
  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:19436656]
  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:17963464]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Urokinase plasminogen activator receptor activity
Specific Function
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-...
Gene Name
PLAUR
Uniprot ID
Q03405
Uniprot Name
Urokinase plasminogen activator surface receptor
Molecular Weight
36977.62 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
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. [PubMed:17963464]

Drug created on June 13, 2005 07:24 / Updated on November 06, 2017 06:43