Tenecteplase

Identification

Summary

Tenecteplase is a modified form of recombinant human tissue plasminogen activator used in the emergency treatment of myocardial infarction and pulmonary emboli.

Brand Names
Metalyse, Tnkase
Generic Name
Tenecteplase
DrugBank Accession Number
DB00031
Background

Tenecteplase is a tissue plasminogen activator (tPA) developed from modifications of natural human tPA complementary DNA (cDNA). It is a 527 amino acid with a substitution of threonine 103 with asparagine and substitution of asparagine 117 with glutamine within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296-299 in the protease domain.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Thrombolytic agents
Protein Structure
Protein Chemical Formula
C2561H3919N747O781S40
Protein Average Weight
58951.2 Da
Sequences
>DB00031 sequence
SYQVICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGG
TCQQALYFSDFVCQCPEGFAGKCCEIDTRATCYEDQGISYRGNWSTAESGAECTNWQSSA
LAQKPYSGRRPDAIRLGLGNHNYCRNPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDC
YFGNGSAYRGTHSLTESGASCLPWNSMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAK
PWCHVLKNRRLTWEYCDVPSCSTCGLRQYSQPQFRIKGGLFADIASHPWQAAIFAAAAAS
PGERFLCGGILISSCWILSAAHCFQERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVH
KEFDDDTYDNDIALLQLKSDSSRCAQESSVVRTVCLPPADLQLPDWTECELSGYGKHEAL
SPFYSERLKEAHVRLYPSSRCTSQHLLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGG
PLVCLNDGRMTLVGIISWGLGCGQKDVPGVYTKVTNYLDWIRDNMRP
Download FASTA Format
Synonyms
  • Tenecteplasa
  • Tenecteplase
  • TNK-tPA

Pharmacology

Indication

For treatment of myocardial infarction and lysis of intracoronary emboli

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Prevention ofCardiovascular mortality•••••••••••••••••••••• •••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Tenecteplase is a fibrin-specific tissue-plasminogen activator. It binds to fibrin rich clots and 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

Tenecteplase 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
Humans
AFibrinogen alpha chainNot AvailableHumans
UUrokinase plasminogen activator surface receptorNot AvailableHumans
UPlasminogen activator inhibitor 1Not AvailableHumans
UPlasminogen activator inhibitor 2Not AvailableHumans
UTetranectinNot AvailableHumans
UKeratin, type II cytoskeletal 8Not AvailableHumans
UAnnexin A2Not AvailableHumans
UCalreticulinNot AvailableHumans
UCalnexinNot AvailableHumans
UProlow-density lipoprotein receptor-related protein 1Not AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

1.9 hours (mammalian reticulocytes, in vitro) >20 hours (yeast, in vivo) >10 hours (Escherichia coli, in vivo)

Clearance
  • 99 - 119 mL/min [acute myocardial infarction patients]
Adverse Effects
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Toxicity

Not Available

Pathways
PathwayCategory
Tenecteplase Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Tenecteplase.
AceclofenacThe risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Tenecteplase.
AcemetacinThe risk or severity of bleeding and hemorrhage can be increased when Tenecteplase is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding can be increased when Tenecteplase is combined with Acenocoumarol.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Tenecteplase.
Food Interactions
  • Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MetalyseInjection, powder, for solution10000 unitsIntravenousBoehringer Ingelheim2016-09-08Not applicableEU flag
MetalyseInjection, powder, for solution8000 unitsIntravenousBoehringer Ingelheim2016-09-08Not applicableEU flag
TNKaseInjection, powder, lyophilized, for solution; Kit52.5 mg/50mgIntravenousGenentech, Inc.2024-01-05Not applicableUS flag
TNKasePowder, for solution50 mg / vialIntravenousHoffmann La Roche2001-10-18Not applicableCanada flag
TNKaseInjection, powder, lyophilized, for solution; Kit52.5 mg/50mgIntravenousGenentech, Inc.2018-11-07Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
TNKaseTenecteplase (50 mg/10mL) + Isopropyl alcohol (0.7 mL/1mL)KitIntravenous; TopicalGenentech, Inc.2000-06-022014-06-30US flag

Categories

ATC Codes
B01AD11 — Tenecteplase
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
WGD229O42W
CAS number
191588-94-0

References

General References
  1. Gurbel PA, Hayes K, Bliden KP, Yoho J, Tantry US: The platelet-related effects of tenecteplase versus alteplase versus reteplase. Blood Coagul Fibrinolysis. 2005 Jan;16(1):1-7. [Article]
  2. Melzer C, Richter C, Rogalla P, Borges AC, Theres H, Baumann G, Laule M: Tenecteplase for the treatment of massive and submassive pulmonary embolism. J Thromb Thrombolysis. 2004 Aug;18(1):47-50. [Article]
  3. Ohman EM, Van de Werf F, Antman EM, Califf RM, de Lemos JA, Gibson CM, Oliverio RL, Harrelson L, McCabe C, DiBattiste P, Braunwald E: Tenecteplase and tirofiban in ST-segment elevation acute myocardial infarction: results of a randomized trial. Am Heart J. 2005 Jul;150(1):79-88. [Article]
  4. De Luca G, Suryapranata H, Chiariello M: Tenecteplase followed by immediate angioplasty is more effective than tenecteplase alone for people with STEMI. Commentary. Evid Based Cardiovasc Med. 2005 Dec;9(4):284-7. Epub 2005 Nov 2. [Article]
  5. Authors unspecified: Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial. Lancet. 2006 Feb 18;367(9510):569-78. [Article]
UniProt
P00750
Genbank
L00153
KEGG Drug
D06070
PubChem Substance
46508657
RxNav
259280
ChEMBL
CHEMBL2108791
Therapeutic Targets Database
DAP000204
PharmGKB
PA164776757
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tenecteplase

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentMyocardial Infarction1
4CompletedTreatmentStroke1
4Not Yet RecruitingTreatmentAcute Ischemic Stroke1
4RecruitingTreatmentAcute Ischemic Stroke1
4RecruitingTreatmentIschemic Stroke1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • F Hoffmann-La Roche Ltd.
  • Genentech Inc.
Dosage Forms
FormRouteStrength
Injection, powder, for solution
Injection, powder, for solutionIntravenous10000 units
Injection, powder, for solutionIntravenous8000 units
Injection, powder, for solutionIntravenous; Parenteral10000 U/10ML
Injection, powder, for solutionIntravenous; Parenteral6000 U/6ML
Injection, powder, for solutionIntravenous; Parenteral8000 U/8ML
PowderIntravenous10000 U/10ML
PowderIntravenous6000 U/6ML
PowderIntravenous8000 U/8ML
SolutionIntravenous30.000 mg
Injection, powder, for solutionIntravenous bolus50 mg
Injection, powder, for solutionParenteral30 mg
Injection, powder, lyophilized, for solutionParenteral40 mg
Injection, powder, for solutionIntravenous10000 u
Injection, powder, lyophilized, for solutionIntravenous50 mg
Injection, powder, for solutionIntravenous
PowderIntravenous
Injection, powder, lyophilized, for solution; kitIntravenous52.5 mg/50mg
KitIntravenous; Topical
Powder, for solutionIntravenous50 mg / vial
PowderIntravenous40 mg/1vial
Prices
Unit descriptionCostUnit
Tnkase 50 mg kit3238.76USD kit
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2129660No2005-06-282013-05-28Canada flag
CA1341432No2003-06-172020-06-17Canada flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)60 °CNovokhatny, V.V. et al., J. Biol. Chem. 266:12994-123002 (1991)
hydrophobicity-0.528Not Available
isoelectric point7.61Not Available

Targets

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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
  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. [Article]
  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. [Article]
  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. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
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
  1. 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. [Article]
  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. [Article]
  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. [Article]
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
  1. Maupas-Schwalm F, Auge N, Robinet C, Cambus JP, Parsons SJ, Salvayre R, Negre-Salvayre A: The sphingomyelin/ceramide pathway is involved in ERK1/2 phosphorylation, cell proliferation, and uPAR overexpression induced by tissue-type plasminogen activator. FASEB J. 2004 Sep;18(12):1398-400. Epub 2004 Jul 1. [Article]
  2. Bankl HC, Samorapoompichit P, Pikula B, Latinovic L, Bankl H, Lechner K, Valent P: Characterization of human prostate mast cells and their increase in periprostatic vein thrombosis. Am J Clin Pathol. 2001 Jul;116(1):97-106. [Article]
  3. Ferrier CM, Van Geloof WL, Straatman H, Van De Molengraft FJ, Van Muijen GN, Ruiter DJ: Spitz naevi may express components of the plasminogen activation system. J Pathol. 2002 Sep;198(1):92-9. [Article]
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
  1. Lindberg P, Kinnby B, Lecander I, Lang NP, Matsson L: Increasing expression of tissue plasminogen activator and plasminogen activator inhibitor type 2 in dog gingival tissues with progressive inflammation. Arch Oral Biol. 2001 Jan;46(1):23-31. [Article]
  2. Hattori M, Azami Y: Searching for preventive measures of cardiovascular events in aged Japanese taxi drivers--the daily rhythm of cardiovascular risk factors during a night duty day. J Hum Ergol (Tokyo). 2001 Dec;30(1-2):321-6. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Inhibits urokinase-type plasminogen activator. The monocyte derived PAI-2 is distinct from the endothelial cell-derived PAI-1.
Gene Name
SERPINB2
Uniprot ID
P05120
Uniprot Name
Plasminogen activator inhibitor 2
Molecular Weight
46595.84 Da
References
  1. Verkleij-Hagoort AC, Ursem NT, Hop WC, Geurts-Moespot A, Steegers EA, Sweep FC, Steegers-Theunissen RP: Complex congenital malformations and the impact of the plasminogen activator system and beta-hCG in amniotic fluid. Eur J Obstet Gynecol Reprod Biol. 2007 Nov;135(1):47-52. Epub 2006 Dec 1. [Article]
  2. Bremer HA, Brommer EJ, Wallenburg HC: Effects of labor and delivery on fibrinolysis. Eur J Obstet Gynecol Reprod Biol. 1994 Jun 30;55(3):163-8. [Article]
  3. Stump DC, Thienpont M, Collen D: Purification and characterization of a novel inhibitor of urokinase from human urine. Quantitation and preliminary characterization in plasma. J Biol Chem. 1986 Sep 25;261(27):12759-66. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Kringle domain binding
Specific Function
Tetranectin binds to plasminogen and to isolated kringle 4. May be involved in the packaging of molecules destined for exocytosis.
Gene Name
CLEC3B
Uniprot ID
P05452
Uniprot Name
Tetranectin
Molecular Weight
22536.665 Da
References
  1. Westergaard UB, Andersen MH, Heegaard CW, Fedosov SN, Petersen TE: Tetranectin binds hepatocyte growth factor and tissue-type plasminogen activator. Eur J Biochem. 2003 Apr;270(8):1850-4. [Article]
  2. Kamper EF, Kopeikina LT, Koutsoukos V, Stavridis J: Plasma tetranectin levels and disease activity in patients with rheumatoid arthritis. J Rheumatol. 1997 Feb;24(2):262-8. [Article]
  3. Vuckovic B, Deric M: [Lipoprotein(a): a link between thrombogenesis and atherogenesis]. Med Pregl. 2007 Jan-Feb;60(1-2):37-41. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Structural molecule activity
Specific Function
Together with KRT19, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle.
Gene Name
KRT8
Uniprot ID
P05787
Uniprot Name
Keratin, type II cytoskeletal 8
Molecular Weight
53703.76 Da
References
  1. Kralovich KR, Li L, Hembrough TA, Webb DJ, Karns LR, Gonias SL: Characterization of the binding sites for plasminogen and tissue-type plasminogen activator in cytokeratin 8 and cytokeratin 18. J Protein Chem. 1998 Nov;17(8):845-54. [Article]
  2. Hembrough TA, Kralovich KR, Li L, Gonias SL: Cytokeratin 8 released by breast carcinoma cells in vitro binds plasminogen and tissue-type plasminogen activator and promotes plasminogen activation. Biochem J. 1996 Aug 1;317 ( Pt 3):763-9. [Article]
  3. Hembrough TA, Li L, Gonias SL: Cell-surface cytokeratin 8 is the major plasminogen receptor on breast cancer cells and is required for the accelerated activation of cell-associated plasminogen by tissue-type plasminogen activator. J Biol Chem. 1996 Oct 11;271(41):25684-91. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
S100 protein binding
Specific Function
Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress resp...
Gene Name
ANXA2
Uniprot ID
P07355
Uniprot Name
Annexin A2
Molecular Weight
38603.63 Da
References
  1. Diaz VM, Hurtado M, Thomson TM, Reventos J, Paciucci R: Specific interaction of tissue-type plasminogen activator (t-PA) with annexin II on the membrane of pancreatic cancer cells activates plasminogen and promotes invasion in vitro. Gut. 2004 Jul;53(7):993-1000. [Article]
  2. Kang HM, Choi KS, Kassam G, Fitzpatrick SL, Kwon M, Waisman DM: Role of annexin II tetramer in plasminogen activation. Trends Cardiovasc Med. 1999 Apr-May;9(3-4):92-102. [Article]
  3. MacLeod TJ, Kwon M, Filipenko NR, Waisman DM: Phospholipid-associated annexin A2-S100A10 heterotetramer and its subunits: characterization of the interaction with tissue plasminogen activator, plasminogen, and plasmin. J Biol Chem. 2003 Jul 11;278(28):25577-84. Epub 2003 Apr 30. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently wit...
Gene Name
CALR
Uniprot ID
P27797
Uniprot Name
Calreticulin
Molecular Weight
48141.2 Da
References
  1. Allen S, Bulleid NJ: Calnexin and calreticulin bind to enzymically active tissue-type plasminogen activator during biosynthesis and are not required for folding to the native conformation. Biochem J. 1997 Nov 15;328 ( Pt 1):113-9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Poly(a) rna binding
Specific Function
Calcium-binding protein that interacts with newly synthesized glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembl...
Gene Name
CANX
Uniprot ID
P27824
Uniprot Name
Calnexin
Molecular Weight
67567.695 Da
References
  1. Allen S, Bulleid NJ: Calnexin and calreticulin bind to enzymically active tissue-type plasminogen activator during biosynthesis and are not required for folding to the native conformation. Biochem J. 1997 Nov 15;328 ( Pt 1):113-9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Receptor activity
Specific Function
Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Required for early embryonic development. Involved in cellular lipid homeostasis. Involved in the plasma clearance...
Gene Name
LRP1
Uniprot ID
Q07954
Uniprot Name
Prolow-density lipoprotein receptor-related protein 1
Molecular Weight
504601.695 Da
References
  1. Moestrup SK, Nielsen S, Andreasen P, Jorgensen KE, Nykjaer A, Roigaard H, Gliemann J, Christensen EI: Epithelial glycoprotein-330 mediates endocytosis of plasminogen activator-plasminogen activator inhibitor type-1 complexes. J Biol Chem. 1993 Aug 5;268(22):16564-70. [Article]
  2. Nykjaer A, Petersen CM, Moller B, Jensen PH, Moestrup SK, Holtet TL, Etzerodt M, Thogersen HC, Munch M, Andreasen PA, et al.: Purified alpha 2-macroglobulin receptor/LDL receptor-related protein binds urokinase.plasminogen activator inhibitor type-1 complex. Evidence that the alpha 2-macroglobulin receptor mediates cellular degradation of urokinase receptor-bound complexes. J Biol Chem. 1992 Jul 25;267(21):14543-6. [Article]
  3. Hu K, Yang J, Tanaka S, Gonias SL, Mars WM, Liu Y: Tissue-type plasminogen activator acts as a cytokine that triggers intracellular signal transduction and induces matrix metalloproteinase-9 gene expression. J Biol Chem. 2006 Jan 27;281(4):2120-7. Epub 2005 Nov 22. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 29, 2024 03:23