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Identification
NameTenecteplase
Accession NumberDB00031  (BIOD00019, BTD00019)
Typebiotech
Groupsapproved
Description

Tissue plasminogen activator (tPA). Tenecteplase is a 527 amino acid glycoprotein developed by introducing the following modifications to the complementary DNA (cDNA) for natural human tPA: a substitution of threonine 103 with asparagine, and a substitution of asparagine 117 with glutamine, both within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296-299 in the protease domain.

Protein structureDb00031
Protein chemical formulaC2561H3919N747O781S40
Protein average weight58951.2000
Sequences
>DB00031 sequence
SYQVICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGG
TCQQALYFSDFVCQCPEGFAGKCCEIDTRATCYEDQGISYRGNWSTAESGAECTQWNSSA
LAQKPYSGRRPDAIRLGLGNHNYCRNPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDC
YFGNGSAYRGTHSLTESGASCLPWNSMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAK
PWCHVLKNRRLTWEYCDVPSCSTCGLRQYSQPQFRIKGGLFADIASHPWQAAAAAKHRRS
PGERFLCGGILISSCWILSAAHCFQERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVH
KEFDDDTYDNDIALLQLKSDSSRCAQESSVVRTVCLPPADLQLPDWTECELSGYGKHEAL
SPFYSERLKEAHVRLYPSSRCTSQHLLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGG
PLVCLNDGRMTLVGIISWGLGCGQKDVPGVYTKVTNYLDWIRDNMRP
Download FASTA Format
Synonyms
SynonymLanguageCode
t- PANot AvailableNot Available
t-plasminogen activatorNot AvailableNot Available
Tissue-type plasminogen activator precursorNot AvailableNot Available
tPANot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
TNKaseGenentech Inc
Brand mixturesNot Available
Categories
CAS number191588-94-0
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor treatment of myocardial infarction and lysis of intracoronary emboli
PharmacodynamicsTenecteplase 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 actionTenecteplase 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half life1.9 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]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Tenecteplase Action PathwayDrug actionSMP00283
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption Not Available Not Available
Blood Brain Barrier Not Available Not Available
Caco-2 permeable Not Available Not Available
P-glycoprotein substrate Not Available Not Available
P-glycoprotein inhibitor I Not Available Not Available
P-glycoprotein inhibitor II Not Available Not Available
Renal organic cation transporter Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 1A2 substrate Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 2C19 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 inhibitory promiscuity Not Available Not Available
Ames test Not Available Not Available
Carcinogenicity Not Available Not Available
Biodegradation Not Available Not Available
Rat acute toxicity Not Available Not applicable
hERG inhibition (predictor I) Not Available Not Available
hERG inhibition (predictor II) Not Available Not Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous
Prices
Unit descriptionCostUnit
Tnkase 50 mg kit3238.76USDkit
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada21296602005-06-282013-05-28
Canada13414322003-06-172020-06-17
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point60 °CNovokhatny, V.V. et al., J. Biol. Chem. 266:12994-123002 (1991)
hydrophobicity-0.528Not Available
isoelectric point7.61Not Available
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  5. : 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. Pubmed
External Links
ResourceLink
UniProtP00750
GenbankL00153
PharmGKBPA164776757
Drug Product Database2244826
RxListhttp://www.rxlist.com/cgi/generic2/tenecteplase.htm
Drugs.comhttp://www.drugs.com/mtm/tenecteplase.html
WikipediaTenecteplase
ATC CodesB01AD11
AHFS Codes
  • 20:12.20
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AprotininAprotonin may antagonize the effect of Tenecteplase. Monitor for decreased effects of Tenecteplase.
Drotrecogin alfaIncreased risk of bleeding.
Ginkgo bilobaAdditive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
GinsengIncreased risk of bleeding.
TiclopidineIncreased bleeding risk. Monitor for signs of bleeding.
Food InteractionsNot Available

1. Plasminogen

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: activator

Components

Name UniProt ID Details
Plasminogen P00747 Details

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

2. Fibrinogen alpha chain

Kind: protein

Organism: Human

Pharmacological action: yes

Components

Name UniProt ID Details
Fibrinogen alpha chain P02671 Details

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. Pubmed
  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
  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

3. Urokinase plasminogen activator surface receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Urokinase plasminogen activator surface receptor Q03405 Details

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. Pubmed
  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. Pubmed
  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. Pubmed

4. Plasminogen activator inhibitor 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Plasminogen activator inhibitor 1 P05121 Details

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. Pubmed
  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. Pubmed
  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

5. Plasminogen activator inhibitor 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Plasminogen activator inhibitor 2 P05120 Details

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. 2006 Nov 30;. Pubmed
  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. Pubmed
  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. Pubmed

6. Tetranectin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tetranectin P05452 Details

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. Pubmed
  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. Pubmed
  3. Vuckovic B, Deric M: [Lipoprotein(a): a link between thrombogenesis and atherogenesis] Med Pregl. 2007 Jan-Feb;60(1-2):37-41. Pubmed

7. Keratin, type II cytoskeletal 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Keratin, type II cytoskeletal 8 P05787 Details

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. Pubmed
  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. Pubmed
  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. Pubmed

8. Annexin A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Annexin A2 P07355 Details

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. Pubmed
  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. Pubmed
  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. Pubmed

9. Calreticulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Calreticulin P27797 Details

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. Pubmed

10. Calnexin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Calnexin P27824 Details

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. Pubmed

11. Prolow-density lipoprotein receptor-related protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Prolow-density lipoprotein receptor-related protein 1 Q07954 Details

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. Pubmed
  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. Pubmed
  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. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 29, 2010 14:34