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

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

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Retavase	Kit			Ekr Therapeutics	1996-10-30	2017-03-14
Retavase	Powder, for solution	10.4 unit	Intravenous	Ekr Therapeutics	1999-02-19	2013-08-29
Retavase	Kit			Chiesi Pharmaceuticals Inc.	1996-10-30	Not applicable
Retavase	Kit			Ekr Therapeutics	1996-10-30	2017-03-14
Retavase	Kit			Chiesi Pharmaceuticals Inc.	1996-10-30	Not applicable

Categories

UNII

DQA630RIE9

CAS number

133652-38-7

Pharmacology

Indication

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

Associated Conditions

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.

Target	Actions	Organism
APlasminogen	activator	Human
AFibrinogen alpha chain	Not Available	Human
UUrokinase plasminogen activator surface receptor	Not Available	Human
UPlasminogen activator inhibitor 1	Not Available	Human

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	Category
Reteplase Action Pathway	Drug action

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction	Drug group
Abciximab	Reteplase may increase the anticoagulant activities of Abciximab.	Approved
Acenocoumarol	Reteplase may increase the anticoagulant activities of Acenocoumarol.	Approved, Investigational
Acetylsalicylic acid	The risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Reteplase.	Approved, Vet Approved
Aloxiprin	The risk or severity of adverse effects can be increased when Aloxiprin is combined with Reteplase.	Experimental
Alprostadil	Alprostadil may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Aminosalicylic Acid	The risk or severity of adverse effects can be increased when Aminosalicylic Acid is combined with Reteplase.	Approved
Anagrelide	Anagrelide may increase the anticoagulant activities of Reteplase.	Approved
Ancrod	Reteplase may increase the anticoagulant activities of Ancrod.	Approved, Investigational
Andrographolide	Andrographolide may increase the anticoagulant activities of Reteplase.	Investigational
Antithrombin III human	Reteplase may increase the anticoagulant activities of Antithrombin III human.	Approved
Apixaban	Reteplase may increase the anticoagulant activities of Apixaban.	Approved
Aprotinin	The therapeutic efficacy of Reteplase can be decreased when used in combination with Aprotinin.	Approved, Investigational, Withdrawn
Ardeparin	Reteplase may increase the anticoagulant activities of Ardeparin.	Approved, Investigational, Withdrawn
Argatroban	Reteplase may increase the anticoagulant activities of Argatroban.	Approved, Investigational
Azelastine	Azelastine may increase the anticoagulant activities of Reteplase.	Approved
Balsalazide	The risk or severity of adverse effects can be increased when Balsalazide is combined with Reteplase.	Approved, Investigational
Becaplermin	Reteplase may increase the anticoagulant activities of Becaplermin.	Approved, Investigational
Beraprost	Beraprost may increase the anticoagulant activities of Reteplase.	Investigational
Bivalirudin	Reteplase may increase the anticoagulant activities of Bivalirudin.	Approved, Investigational
Buflomedil	Buflomedil may increase the anticoagulant activities of Reteplase.	Experimental
Butylphthalide	Butylphthalide may increase the anticoagulant activities of Reteplase.	Investigational
Cangrelor	Cangrelor may increase the anticoagulant activities of Reteplase.	Approved
Carbaspirin calcium	The risk or severity of adverse effects can be increased when Carbaspirin calcium is combined with Reteplase.	Experimental, Investigational
Certoparin	Reteplase may increase the anticoagulant activities of Certoparin.	Approved, Investigational
Cilostazol	Cilostazol may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Citric Acid	Reteplase may increase the anticoagulant activities of Citric Acid.	Approved, Nutraceutical, Vet Approved
Clopidogrel	Clopidogrel may increase the anticoagulant activities of Reteplase.	Approved
Cloricromen	Cloricromen may increase the anticoagulant activities of Reteplase.	Experimental
Dabigatran etexilate	Reteplase may increase the anticoagulant activities of Dabigatran etexilate.	Approved
Dalteparin	Reteplase may increase the anticoagulant activities of Dalteparin.	Approved
Danaparoid	Reteplase may increase the anticoagulant activities of Danaparoid.	Approved, Withdrawn
Darexaban	Reteplase may increase the anticoagulant activities of Darexaban.	Investigational
Defibrotide	Defibrotide may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Dersalazine	The risk or severity of adverse effects can be increased when Dersalazine is combined with Reteplase.	Investigational
Desirudin	Reteplase may increase the anticoagulant activities of Desirudin.	Approved
Dextran	Reteplase may increase the anticoagulant activities of Dextran.	Approved, Investigational, Vet Approved
Dicoumarol	Reteplase may increase the anticoagulant activities of Dicoumarol.	Approved
Diflunisal	The risk or severity of adverse effects can be increased when Diflunisal is combined with Reteplase.	Approved, Investigational
Dipyridamole	Dipyridamole may increase the anticoagulant activities of Reteplase.	Approved
Edetic Acid	Reteplase may increase the anticoagulant activities of Edetic Acid.	Approved, Vet Approved
Edoxaban	Reteplase may increase the anticoagulant activities of Edoxaban.	Approved
Enoxaparin	Reteplase may increase the anticoagulant activities of Enoxaparin.	Approved
Epinastine	Epinastine may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Eplivanserin	Eplivanserin may increase the anticoagulant activities of Reteplase.	Investigational
eplivanserine	eplivanserine may increase the anticoagulant activities of Reteplase.	Investigational
Epoprostenol	Epoprostenol may increase the anticoagulant activities of Reteplase.	Approved
Eptifibatide	Eptifibatide may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Ethyl biscoumacetate	Reteplase may increase the anticoagulant activities of Ethyl biscoumacetate.	Withdrawn
Ferulic acid	Reteplase may increase the anticoagulant activities of Ferulic acid.	Experimental
Fluindione	Reteplase may increase the anticoagulant activities of Fluindione.	Approved, Investigational
Fondaparinux	Reteplase may increase the anticoagulant activities of Fondaparinux.	Approved, Investigational
Fondaparinux sodium	Reteplase may increase the anticoagulant activities of Fondaparinux sodium.	Approved, Investigational
Gabexate	Reteplase may increase the anticoagulant activities of Gabexate.	Investigational
Guacetisal	The risk or severity of adverse effects can be increased when Guacetisal is combined with Reteplase.	Experimental
Hemoglobin crosfumaril	The risk or severity of adverse effects can be increased when Hemoglobin crosfumaril is combined with Reteplase.	Experimental
Heparin	Reteplase may increase the anticoagulant activities of Heparin.	Approved, Investigational
Hydroxytyrosol	Hydroxytyrosol may increase the anticoagulant activities of Reteplase.	Investigational
Ibudilast	Ibudilast may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Icosapent ethyl	Icosapent ethyl may increase the anticoagulant activities of Reteplase.	Approved, Investigational, Nutraceutical
Idraparinux	Reteplase may increase the anticoagulant activities of Idraparinux.	Investigational
Ifenprodil	Ifenprodil may increase the anticoagulant activities of Reteplase.	Approved, Investigational, Withdrawn
Ifetroban	Ifetroban may increase the anticoagulant activities of Reteplase.	Investigational
Iloprost	Iloprost may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Indobufen	Indobufen may increase the anticoagulant activities of Reteplase.	Investigational
Ketanserin	Ketanserin may increase the anticoagulant activities of Reteplase.	Investigational
Lepirudin	Reteplase may increase the anticoagulant activities of Lepirudin.	Approved
Letaxaban	Reteplase may increase the anticoagulant activities of Letaxaban.	Investigational
Limaprost	The risk or severity of adverse effects can be increased when Limaprost is combined with Reteplase.	Approved, Investigational
Linsidomine	Linsidomine may increase the anticoagulant activities of Reteplase.	Experimental
Melagatran	Reteplase may increase the anticoagulant activities of Melagatran.	Experimental
Mesalazine	The risk or severity of adverse effects can be increased when Mesalazine is combined with Reteplase.	Approved
Methyl salicylate	The risk or severity of adverse effects can be increased when Methyl salicylate is combined with Reteplase.	Approved, Vet Approved
Milrinone	Milrinone may increase the anticoagulant activities of Reteplase.	Approved
Nadroparin	Reteplase may increase the anticoagulant activities of Nadroparin.	Approved, Investigational
Nafamostat	Reteplase may increase the anticoagulant activities of Nafamostat.	Approved, Investigational
Naftopidil	Naftopidil may increase the anticoagulant activities of Reteplase.	Investigational
Nimesulide	Nimesulide may increase the anticoagulant activities of Reteplase.	Approved, Investigational, Withdrawn
Nitroaspirin	The risk or severity of adverse effects can be increased when Nitroaspirin is combined with Reteplase.	Investigational
Olsalazine	The risk or severity of adverse effects can be increased when Olsalazine is combined with Reteplase.	Approved
Otamixaban	Reteplase may increase the anticoagulant activities of Otamixaban.	Investigational
Pentaerythritol Tetranitrate	Reteplase may increase the anticoagulant activities of Pentaerythritol Tetranitrate.	Approved
Pentosan Polysulfate	Reteplase may increase the anticoagulant activities of Pentosan Polysulfate.	Approved
Pentoxifylline	Pentoxifylline may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Phenindione	Reteplase may increase the anticoagulant activities of Phenindione.	Approved, Investigational
Phenprocoumon	Reteplase may increase the anticoagulant activities of Phenprocoumon.	Approved, Investigational
Phenyl aminosalicylate	The risk or severity of adverse effects can be increased when Phenyl aminosalicylate is combined with Reteplase.	Approved
Picotamide	Picotamide may increase the anticoagulant activities of Reteplase.	Experimental
Potassium Citrate	Reteplase may increase the anticoagulant activities of Potassium Citrate.	Approved, Investigational, Vet Approved
Prasugrel	Prasugrel may increase the anticoagulant activities of Reteplase.	Approved
Protein C	Reteplase may increase the anticoagulant activities of Protein C.	Approved
Protein S human	Reteplase may increase the anticoagulant activities of Protein S human.	Approved
Protocatechualdehyde	Reteplase may increase the anticoagulant activities of Protocatechualdehyde.	Approved
Ramatroban	Ramatroban may increase the anticoagulant activities of Reteplase.	Investigational
Relcovaptan	Relcovaptan may increase the anticoagulant activities of Reteplase.	Investigational
Resveratrol	Resveratrol may increase the anticoagulant activities of Reteplase.	Approved, Experimental, Investigational
Reviparin	Reteplase may increase the anticoagulant activities of Reviparin.	Approved, Investigational
Ridogrel	Ridogrel may increase the anticoagulant activities of Reteplase.	Approved
Rivaroxaban	Reteplase may increase the anticoagulant activities of Rivaroxaban.	Approved
Salicylic acid	The risk or severity of adverse effects can be increased when Salicylic acid is combined with Reteplase.	Approved, Investigational, Vet Approved
Sarpogrelate	Sarpogrelate may increase the anticoagulant activities of Reteplase.	Investigational
Sevoflurane	Sevoflurane may increase the anticoagulant activities of Reteplase.	Approved, Vet Approved
Sodium Citrate	Reteplase may increase the anticoagulant activities of Sodium Citrate.	Approved, Investigational
SRT501	SRT501 may increase the anticoagulant activities of Reteplase.	Investigational
Sulodexide	Reteplase may increase the anticoagulant activities of Sulodexide.	Approved, Investigational
Tesmilifene	Tesmilifene may increase the anticoagulant activities of Reteplase.	Investigational
Ticagrelor	Ticagrelor may increase the anticoagulant activities of Reteplase.	Approved
Ticlopidine	Ticlopidine may increase the anticoagulant activities of Reteplase.	Approved
Tirofiban	Tirofiban may increase the anticoagulant activities of Reteplase.	Approved
Tranilast	Tranilast may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Trapidil	Trapidil may increase the anticoagulant activities of Reteplase.	Approved
Treprostinil	The risk or severity of adverse effects can be increased when Reteplase is combined with Treprostinil.	Approved, Investigational
Triflusal	Triflusal may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Trolamine salicylate	The risk or severity of adverse effects can be increased when Trolamine salicylate is combined with Reteplase.	Approved
Troxerutin	Reteplase may increase the anticoagulant activities of Troxerutin.	Investigational
Vorapaxar	Vorapaxar may increase the anticoagulant activities of Reteplase.	Approved
Warfarin	Reteplase may increase the anticoagulant activities of Warfarin.	Approved
Ximelagatran	Reteplase 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

Phase	Status	Purpose	Conditions	Count
1	Active Not Recruiting	Treatment	Peritoneal dialysis therapy / Peritoneal Dialysis, Continuous Ambulatory	1
1	Withdrawn	Treatment	Stroke, Ischemic	1
1, 2	Unknown Status	Treatment	Acute Myelogenous Leukaemia (AML) / Myelodysplastic Syndrome	1
2	Active Not Recruiting	Treatment	Stroke, Ischemic	1
2	Completed	Treatment	Acute Peripheral Arterial Occlusion	1
2	Completed	Treatment	Cerebrovascular Accidents	1
2	Recruiting	Treatment	Stroke, Ischemic	1
2	Terminated	Treatment	Leukemias	1
2	Terminated	Treatment	Strokes	1
2, 3	Recruiting	Treatment	Exudative Macular Degeneration / Retinal Hemorrhage	1
2, 3	Terminated	Treatment	Abscesses	1
3	Completed	Treatment	Pleural Empyema	1
3	Recruiting	Treatment	Strokes	2
Not Available	Completed	Treatment	Bacterial Pleural Effusion Other Than Tuberculosis / Pleural Effusion Associated With Pulmonary Infection	1
Not Available	Completed	Treatment	Prosthetic Valve Thrombosis	1
Not Available	Recruiting	Not Available	Strokes	1
Not Available	Recruiting	Treatment	Ischemia, Brain / Strokes	1
Not Available	Recruiting	Treatment	Kidney Diseases	1
Not Available	Terminated	Treatment	Catheter Malfunction / Clotted Dialysis Catheter / Dialysis Catheter Fibrin Sheath	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

EKR Therapeutics Inc.
Hospira Inc.
PDL BioPharma Inc.

Dosage forms

Form	Route	Strength
Kit
Powder, for solution	Intravenous	10.4 unit

Prices

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

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
CA2107476	No	2007-12-18	2012-04-15

Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	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

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

Details1. Plasminogen

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

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]
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]
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]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Details2. Fibrinogen alpha chain

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

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]
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]
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]

Details3. Urokinase plasminogen activator surface receptor

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

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]
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]

Details4. Plasminogen activator inhibitor 1

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

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 June 02, 2018 06:29