Reteplase - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Taxonomy

Targets (4)

Targets (4)Biointeractions (1)

Identification

Name

Reteplase

Accession Number

DB00015 (BTD00013, BIOD00013)

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

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

Product Ingredients

Not Available

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Retavase	Kit			Ekr Therapeutics	1996-10-30	2017-03-14	US
Retavase	Kit			Ekr Therapeutics	1996-10-30	2017-03-14	US
Retavase	Powder, for solution	10.4 unit	Intravenous	Ekr Therapeutics	1999-02-19	2013-08-29	Canada

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Not Available

Brand mixtures

Not Available

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.

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
Plasminogen	Protein	yes	activator	Human	P00747	details
Fibrinogen alpha chain	Protein	yes	Not Available	Human	P02671	details
Urokinase plasminogen activator surface receptor	Protein	unknown	Not Available	Human	Q03405	details
Plasminogen activator inhibitor 1	Protein	unknown	Not Available	Human	P05121	details

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	SMPDB ID
Reteplase Action Pathway	Drug action	SMP00285

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
Acetylsalicylic acid	The risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Reteplase.	Approved, Vet Approved
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.	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, Withdrawn
Ardeparin	Reteplase may increase the anticoagulant activities of Ardeparin.	Approved, 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
Cangrelor	Cangrelor may increase the anticoagulant activities of Reteplase.	Approved
Certoparin	Reteplase may increase the anticoagulant activities of Certoparin.	Approved
Cilostazol	Cilostazol may increase the anticoagulant activities of Reteplase.	Approved
Citric Acid	Reteplase may increase the anticoagulant activities of Citric Acid.	Nutraceutical, Vet Approved
Clopidogrel	Clopidogrel may increase the anticoagulant activities of Reteplase.	Approved, Nutraceutical
Dabigatran etexilate	Reteplase may increase the anticoagulant activities of Dabigatran etexilate.	Approved
Dalteparin	Reteplase may increase the anticoagulant activities of Dalteparin.	Approved
Defibrotide	Defibrotide may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Desirudin	Reteplase may increase the anticoagulant activities of Desirudin.	Approved
Dextran	Reteplase may increase the anticoagulant activities of Dextran.	Approved, Vet Approved
Dextran 40	Reteplase may increase the anticoagulant activities of Dextran 40.	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
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
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
Fondaparinux sodium	Reteplase may increase the anticoagulant activities of Fondaparinux sodium.	Approved, Investigational
Gabexate	Reteplase may increase the anticoagulant activities of Gabexate.	Investigational
Heparin	Reteplase may increase the anticoagulant activities of Heparin.	Approved, Investigational
Ibudilast	Ibudilast may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Icosapent ethyl	Icosapent ethyl may increase the anticoagulant activities of Reteplase.	Approved, Nutraceutical
Ifenprodil	Ifenprodil may increase the anticoagulant activities of Reteplase.	Approved, Withdrawn
Iloprost	Iloprost may increase the anticoagulant activities of Reteplase.	Approved, Investigational
Lepirudin	Reteplase may increase the anticoagulant activities of Lepirudin.	Approved
Limaprost	The risk or severity of adverse effects can be increased when Limaprost is combined with Reteplase.	Approved
Mesalazine	The risk or severity of adverse effects can be increased when Mesalazine is combined with Reteplase.	Approved
Milrinone	Milrinone may increase the anticoagulant activities of Reteplase.	Approved
Nadroparin	Reteplase may increase the anticoagulant activities of Nadroparin.	Approved
Nafamostat	Reteplase may increase the anticoagulant activities of Nafamostat.	Approved, Investigational
NCX 4016	The risk or severity of adverse effects can be increased when NCX 4016 is combined with Reteplase.	Investigational
Nimesulide	Nimesulide may increase the anticoagulant activities of Reteplase.	Approved, Withdrawn
Olsalazine	The risk or severity of adverse effects can be increased when Olsalazine is combined with Reteplase.	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
Phenprocoumon	Reteplase may increase the anticoagulant activities of Phenprocoumon.	Approved
Prasugrel	Prasugrel may increase the anticoagulant activities of Reteplase.	Approved
Protein S human	Reteplase may increase the anticoagulant activities of Protein S human.	Approved
Resveratrol	Resveratrol may increase the anticoagulant activities of Reteplase.	Experimental, Investigational
Reviparin	Reteplase may increase the anticoagulant activities of Reviparin.	Approved
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, Vet Approved
Sevoflurane	Sevoflurane may increase the anticoagulant activities of Reteplase.	Approved, Vet Approved
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
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
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

Synthesis Reference

Not Available

General References

Not Available

External Links

Resource	Link
UniProt	P00750
Genbank	L00153
PharmGKB	PA164743728
Drug Product Database	11534
RxList	http://www.rxlist.com/cgi/generic2/reteplase.htm
Drugs.com	http://www.drugs.com/cdi/reteplase.html
Wikipedia	Reteplase

ATC Codes

B01AD07

AHFS Codes

Not Available

PDB Entries

1BDA

FDA label

Not Available

MSDS

Not Available

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	Completed	Treatment	Acute Peripheral Arterial Occlusion	1
2	Completed	Treatment	Cerebrovascular Accidents	1
2	Not Yet Recruiting	Treatment	Plastic Bronchitis	1
2	Recruiting	Treatment	Stroke, Ischemic	2
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	Recruiting	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

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	Canada

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

Details

1. 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 ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin ...
Gene Name:: PLG
Uniprot ID:: P00747
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 ]

Details

2. 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 in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelializati...
Gene Name:: FGA
Uniprot ID:: P02671
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 ]

Details

3. 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-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.
Gene Name:: PLAUR
Uniprot ID:: Q03405
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 ]

Details

4. 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 control point in the regulation of fibrinolysis.
Gene Name:: SERPINE1
Uniprot ID:: P05121
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 08, 2017 11:14

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Targets

References

References

References

References