Identification

Name
Reteplase
Accession Number
DB00015  (BTD00013, BIOD00013)
Type
Biotech
Groups
Approved, Investigational
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)
  • Reteplasa
  • Reteplase, recombinant
  • Reteplase,recombinant
External IDs
BM 06.022 / BM-06.022 / BM-06022
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RetavasePowder, for solution10.4 unitIntravenousEkr Therapeutics1999-02-192013-08-29Canada
RetavaseKit1.81 mg/1mLChiesi Pharmaceuticals Inc.1996-10-30Not applicableUs
RetavaseKit1.81 mg/1mLEkr Therapeutics1996-10-302017-07-01Us
RetavaseKit1.81 mg/1mLChiesi Pharmaceuticals Inc.1996-10-30Not applicableUs
RetavaseKit1.81 mg/1mLEkr Therapeutics1996-10-302017-07-01Us
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.

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
DrugInteraction
(1,2,6,7-3H)TestosteroneThe therapeutic efficacy of Reteplase can be increased when used in combination with (1,2,6,7-3H)Testosterone.
(R)-warfarinThe risk or severity of bleeding can be increased when Reteplase is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Reteplase is combined with (S)-Warfarin.
1-TestosteroneThe therapeutic efficacy of Reteplase can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Reteplase can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Reteplase is combined with 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Reteplase can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Reteplase can be increased when used in combination with 5beta-dihydrotestosterone.
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.
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, 2TerminatedTreatmentAcute Myelogenous Leukaemia (AML) / Myelodysplastic Syndrome1
2Active Not RecruitingTreatmentStroke, Ischemic1
2CompletedTreatmentAcute Peripheral Arterial Occlusion1
2CompletedTreatmentCerebrovascular Accidents1
2RecruitingTreatmentStroke, Ischemic1
2TerminatedTreatmentLeukemias1
2TerminatedTreatmentStrokes1
2, 3RecruitingTreatmentExudative Macular Degeneration / Retinal Hemorrhage1
2, 3TerminatedTreatmentAbscesses1
3CompletedTreatmentPleural Empyema1
3CompletedTreatmentStrokes2
3Not Yet RecruitingTreatmentCatheter Occlusion / Thrombotic events1
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
  • EKR Therapeutics Inc.
  • Hospira Inc.
  • PDL BioPharma Inc.
Dosage forms
FormRouteStrength
Kit1.81 mg/1mL
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 December 01, 2018 19:13