DT-Web

DB00031 - Tenecteplase


Identification
Name Tenecteplase
Accession Number DB00031 (BIOD00019, BTD00019)
Type biotech
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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 58951.2000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For treatment of myocardial infarction and lysis of intracoronary emboli
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.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Aprotinin Aprotonin may antagonize the effect of Tenecteplase. Monitor for decreased effects of Tenecteplase.
Drotrecogin alfa Increased risk of bleeding.
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Ginseng Increased risk of bleeding.
Ticlopidine Increased bleeding risk. Monitor for signs of bleeding.
Food Interactions Not Available

Targets


Plasminogen
Name Plasminogen
Gene Name PLG
Pharmacological action yes
Actions activator
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
  • 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
  • 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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.7594
Fibrinogen alpha chain
Name Fibrinogen alpha chain
Gene Name FGA
Pharmacological action yes
Actions Not Available
References
  • 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
  • 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
  • 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
DTHybrid score 1.5106
Urokinase plasminogen activator surface receptor
Name Urokinase plasminogen activator surface receptor
Gene Name PLAUR
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
  • 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
DTHybrid score 1.6824
Plasminogen activator inhibitor 1
Name Plasminogen activator inhibitor 1
Gene Name SERPINE1
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
  • 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
DTHybrid score 1.5907
Plasminogen activator inhibitor 2
Name Plasminogen activator inhibitor 2
Gene Name SERPINB2
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
  • 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
DTHybrid score 0.9995
Tetranectin
Name Tetranectin
Gene Name CLEC3B
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
  • Vuckovic B, Deric M: [Lipoprotein(a): a link between thrombogenesis and atherogenesis] Med Pregl. 2007 Jan-Feb;60(1-2):37-41. - Pubmed
DTHybrid score 0.9349
Keratin, type II cytoskeletal 8
Name Keratin, type II cytoskeletal 8
Gene Name KRT8
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
  • 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
DTHybrid score 0.9346
Annexin A2
Name Annexin A2
Gene Name ANXA2
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
  • 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
DTHybrid score 0.9346
Calreticulin
Name Calreticulin
Gene Name CALR
Pharmacological action unknown
Actions Not Available
References
  • 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
DTHybrid score 0.9286
Calnexin
Name Calnexin
Gene Name CANX
Pharmacological action unknown
Actions Not Available
References
  • 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
DTHybrid score 0.9755
Low-density lipoprotein receptor-related protein 1
Name Low-density lipoprotein receptor-related protein 1
Gene Name LRP1
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
  • 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
DTHybrid score 0.9873

Predictions


Id Partner name Gene Name Score
3834 Nidogen-1 NID1 0.2076
3833 Plasma serine protease inhibitor SERPINA5 0.207
1792 Tissue-type plasminogen activator PLAT 0.1871
3842 Multiple coagulation factor deficiency protein 2 MCFD2 0.1841
3840 Asialoglycoprotein receptor 2 ASGR2 0.184
1847 78 kDa glucose-regulated protein HSPA5 0.1839
3841 ERGIC-53 protein LMAN1 0.1839
1635 von Willebrand factor VWF 0.1838
3011 Suppressor of tumorigenicity protein 14 ST14 0.179
400 Coagulation factor IX F9 0.1576
5461 Coagulation factor IX F9 0.1576
3839 Phytanoyl-CoA dioxygenase, peroxisomal PHYH 0.1569
1244 Low-density lipoprotein receptor-related protein 2 LRP2 0.1562
422 Vitamin K-dependent protein C PROC 0.1442
239 Coagulation factor X F10 0.1341
54 Prothrombin F2 0.1221
19 Coagulation factor VIII F8 0.1138
1074 Urokinase-type plasminogen activator PLAU 0.1013
1193 Proteinase-activated receptor 1 F2R 0.0899
448 Vitamin K-dependent gamma-carboxylase GGCX 0.088
2876 Membrane-bound lytic murein transglycosylase B mltB 0.0726
3133 UDP-galactopyranose mutase glf 0.0725
5099 UDP-galactopyranose mutase glf 0.0725
1812 Kallikrein-1 KLK1 0.0676
2353 Apolipoprotein(a) LPA 0.0654
1547 Coagulation factor XI F11 0.065
369 Coagulation factor VII F7 0.0614
3812 Fibrinogen beta chain [Contains: Fibrinopeptide B] FGB 0.0581
3813 Fibrinogen gamma chain FGG 0.0581
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.0573
723 Cytosolic phospholipase A2 PLA2G4A 0.05
1278 Pro-epidermal growth factor EGF 0.0487
6034 Hydroxyindole O-methyltransferase ASMT 0.0393
6035 Nuclear receptor ROR-beta RORB 0.0393
6036 Eosinophil peroxidase EPX 0.0393
1525 Heparin-binding growth factor 2 FGF2 0.0385
6231 Pepsin A PGA3 0.0383
6011 Chymotrypsinogen B CTRB1 0.0359
6020 Aldehyde oxidase AOX1 0.0358
765 Indoleamine 2,3-dioxygenase IDO1 0.0333
3865 Serpin B6 SERPINB6 0.03
571 Melatonin receptor type 1A MTNR1A 0.03
362 Melatonin receptor type 1B MTNR1B 0.03
1959 Platelet factor 4 PF4 0.03
1986 Ceruloplasmin CP 0.0299
2021 Thrombomodulin THBD 0.0254
46 Coagulation factor V F5 0.0254
2072 Endothelial protein C receptor PROCR 0.0253
3176 Trypsin-1 PRSS1 0.0248
3811 Cytochrome P450 19A1 CYP19A1 0.0233
1245 Vitamin K-dependent protein S PROS1 0.0232
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0212
587 Serum albumin ALB 0.0203
6024 Cytochrome P450 1A1 CYP1A1 0.02
1757 Myeloperoxidase MPO 0.019
465 Calmodulin CALM1 0.0186
1898 Cytochrome P450 1B1 CYP1B1 0.0176
6016 Cytochrome P450 2C19 CYP2C19 0.0168
4757 Cytochrome P450 2C9 CYP2C9 0.0159
136 Estrogen receptor ESR1 0.0154
6142 Solute carrier family 22 member 8 SLC22A8 0.0147
6221 Steroid hormone receptor ERR1 ESRRA 0.0127
1457 Long-chain-fatty-acid--CoA ligase 4 ACSL4 0.0116
4200 Cytochrome P450 1A2 CYP1A2 0.0116
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.01
6177 UDP-glucuronosyltransferase 1-10 UGT1A10 0.01
3809 Estrogen-related receptor gamma ESRRG 0.0097
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.009
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0088
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0077
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0072
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0072
776 Bile salt export pump ABCB11 0.007
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.007
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0069
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0063
4878 Glycoprotein hormones alpha chain CGA 0.0062
4877 Beta-mannanase man 0.0062
4869 Major capsid protein A430L 0.0062
4871 Endo-beta-N-acetylglucosaminidase F3 endOF3 0.0062
4850 Beta-2-glycoprotein 1 APOH 0.0062
4880 Membrane cofactor protein CD46 0.0062
1052 Cytotoxic T-lymphocyte protein 4 CTLA4 0.0062
4856 CD209 antigen CD209 0.0062
4889 Ig epsilon chain C region IGHE 0.0062
4189 Alpha-galactosidase A GLA 0.0062
1072 Granzyme B GZMB 0.0062
4852 Reticulon-4 receptor RTN4R 0.0061
757 Fusion glycoprotein F0 F 0.0061
4875 Fusion glycoprotein F0 F 0.0061
4721 Beta-1,4-mannanase manA 0.0061
1563 Platelet glycoprotein Ib alpha chain GP1BA 0.0061
1354 Beta-glucuronidase GUSB 0.0061
442 Envelope glycoprotein gp41 0.0061
4859 Envelope glycoprotein env 0.0061
4845 ADAM 33 ADAM33 0.0061
4882 Dipeptidyl aminopeptidase-like protein 6 DPP6 0.0061
3352 Structural polyprotein Not Available 0.0061
3628 Structural polyprotein Not Available 0.0061
4892 Structural polyprotein Not Available 0.0061
6107 Cytochrome P450 3A7 CYP3A7 0.0055
6030 Cytochrome P450 2B6 CYP2B6 0.0054
793 T-cell surface antigen CD2 CD2 0.0054
4861 Interleukin-6 receptor alpha chain IL6R 0.0054
119 Carcinoembryonic antigen-related cell adhesion molecule 1 CEACAM1 0.0054
4193 Atrial natriuretic peptide clearance receptor NPR3 0.0054
3837 Cytokine receptor common beta chain CSF2RB 0.0054
1184 Interferon beta IFNB1 0.0052
4857 Zinc-alpha-2-glycoprotein AZGP1 0.0052
6858 Inactive carboxylesterase 4 CES1P1 0.0052
1379 Interleukin-12 subunit beta IL12B 0.0052
554 Low-density lipoprotein receptor LDLR 0.0052
4890 Hemagglutinin HA 0.0052
6566 Hemagglutinin Not Available 0.0052
4118 Cytochrome P450 3A5 CYP3A5 0.0051
4924 Cytochrome P450 2C8 CYP2C8 0.005
2998 Sialic acid-binding Ig-like lectin 7 SIGLEC7 0.0048
852 Heparin cofactor 2 SERPIND1 0.0048
6120 Cation-independent mannose-6-phosphate receptor IGF2R 0.0048
2297 Genome polyprotein Not Available 0.0048
2322 Genome polyprotein Not Available 0.0048
2694 Genome polyprotein Not Available 0.0048
2719 Genome polyprotein Not Available 0.0048
2860 Genome polyprotein Not Available 0.0048
2928 Genome polyprotein Not Available 0.0048
3160 Genome polyprotein Not Available 0.0048
3260 Genome polyprotein Not Available 0.0048
4783 Genome polyprotein Not Available 0.0048
5726 Genome polyprotein Not Available 0.0048
5779 Genome polyprotein Not Available 0.0048
5867 Genome polyprotein Not Available 0.0048
6253 Genome polyprotein Not Available 0.0048
6301 Genome polyprotein Not Available 0.0048
6380 Genome polyprotein Not Available 0.0048
6381 Genome polyprotein Not Available 0.0048
6437 Genome polyprotein Not Available 0.0048
6520 Genome polyprotein Not Available 0.0048
6521 Genome polyprotein Not Available 0.0048
6652 Genome polyprotein Not Available 0.0048
6734 Genome polyprotein Not Available 0.0048
6735 Genome polyprotein Not Available 0.0048
6736 Genome polyprotein Not Available 0.0048
6737 Genome polyprotein Not Available 0.0048
6738 Genome polyprotein Not Available 0.0048
6739 Genome polyprotein Not Available 0.0048
6744 Genome polyprotein Not Available 0.0048
6748 Genome polyprotein Not Available 0.0048
6894 Genome polyprotein Not Available 0.0048
6898 Genome polyprotein Not Available 0.0048
18 High affinity immunoglobulin epsilon receptor subunit alpha FCER1A 0.0048
3444 Cyanovirin-N Not Available 0.0047
3258 Mannosyl-oligosaccharide alpha-1,2-mannosidase MSDC 0.0047
3140 Hemagglutinin-neuraminidase HN 0.0047
3609 Hemagglutinin-neuraminidase HN 0.0047
1859 Prostatic acid phosphatase ACPP 0.0047
4787 Envelope glycoprotein gp160 env 0.0045
4820 Envelope glycoprotein gp160 env 0.0045
5727 Envelope glycoprotein gp160 env 0.0045
4666 Fucose-binding lectin PA-IIL lecB 0.0045
2372 Bifunctional tail protein 9 0.0045
2577 Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase MAN1B1 0.0042
3480 Mannan endo-1,4-beta-mannosidase manA 0.0041
64 Neuraminidase NA 0.0041
641 Neuraminidase NA 0.0041
2676 Neuraminidase NA 0.0041
3026 Neuraminidase NA 0.0041
3519 Neuraminidase NA 0.0041
6007 Neuraminidase NA 0.0041
4512 Cytochrome P450 3A4 CYP3A4 0.004
1439 Lactotransferrin LTF 0.0039
1782 Neutrophil gelatinase-associated lipocalin LCN2 0.0039
1243 Cathepsin D CTSD 0.0039
958 Insulin-like growth factor 1 receptor IGF1R 0.0039
309 Antithrombin-III SERPINC1 0.0038
2430 Chondroitinase B cslB 0.0037
2581 Chondroitinase AC cslA 0.0037
6847 Lactase-phlorizin hydrolase LCT 0.0037
6307 Ig gamma-2 chain C region IGHG2 0.0037
6500 Phospholipase A2 PLA2G1B 0.0035
2207 Rhodopsin RHO 0.0034
3814 Complement C1r subcomponent C1R 0.0034
4785 Ig gamma-1 chain C region IGHG1 0.003
4604 Liver carboxylesterase 1 CES1 0.003
76 Nitric-oxide synthase, brain NOS1 0.003
952 Dipeptidyl peptidase 4 DPP4 0.0026
3923 Cholinesterase BCHE 0.0025
20 Prostaglandin G/H synthase 1 PTGS1 0.0023
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