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

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Synonyms

Human t-PA (residues 1-3 and 176-527)
Reteplasa
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
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Retavase	Kit	1.81 mg/1mL		Ekr Therapeutics	1996-10-30	2017-07-01
Retavase	Kit	1.81 mg/1mL		Chiesi Pharmaceuticals Inc.	1996-10-30	Not applicable
Retavase	Kit	1.81 mg/1mL		Chiesi Pharmaceuticals Inc.	1996-10-30	Not applicable
Retavase	Powder, for solution	10.4 unit	Intravenous	Ekr Therapeutics	1999-02-19	2013-08-29
Retavase	Kit	1.81 mg/1mL		Ekr Therapeutics	1996-10-30	2017-07-01

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Application Number

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Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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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	Humans
AFibrinogen alpha chain	Not Available	Humans
UUrokinase plasminogen activator surface receptor	Not Available	Humans
UPlasminogen activator inhibitor 1	Not Available	Humans

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Additional Data Available

Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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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
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(1,2,6,7-3H)Testosterone	The therapeutic efficacy of Reteplase can be increased when used in combination with (1,2,6,7-3H)Testosterone.
(R)-warfarin	The risk or severity of bleeding can be increased when Reteplase is combined with (R)-warfarin.
(S)-Warfarin	The risk or severity of bleeding can be increased when Reteplase is combined with (S)-Warfarin.
1-Testosterone	The therapeutic efficacy of Reteplase can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosterone	The therapeutic efficacy of Reteplase can be increased when used in combination with 18-methyl-19-nortestosterone.
3,5-diiodothyropropionic acid	3,5-diiodothyropropionic acid may increase the anticoagulant activities of Reteplase.
4-hydroxycoumarin	The risk or severity of bleeding can be increased when Reteplase is combined with 4-hydroxycoumarin.
4-Hydroxytestosterone	The therapeutic efficacy of Reteplase can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosterone	The therapeutic efficacy of Reteplase can be increased when used in combination with 5beta-dihydrotestosterone.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline	The risk or severity of bleeding and hemorrhage can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Reteplase.

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Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

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Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

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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
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	Terminated	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	Active Not Recruiting	Treatment	Exudative Macular Degeneration / Retinal Hemorrhage	1
2, 3	Terminated	Treatment	Abscesses	1
3	Completed	Treatment	Pleural Empyema	1
3	Completed	Treatment	Strokes	2
3	Not Yet Recruiting	Treatment	Catheter Occlusion / Thrombotic events	1
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		1.81 mg/1mL
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)
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CA2107476	No	2007-12-18	2012-04-15

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Filed On

The date on which a patent was filed with the relevant government.

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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: 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

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: 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

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: Humans
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: 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

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 04, 2019 04:50