1. Tenecteplase Drugbank ID : DB00031
Protein chemical formula : C2561H3919N747O781S40
Protein average weight :
Half life : 1.9 hours (mammalian reticulocytes, in vitro)

2. Description : Indication : Pharmacodynamics :
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 in the protease domain.
Indication :
For treatment of myocardial infarction and lysis of intracoronary emboli
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.

3. Mechanism of action : Clearance :
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.
Clearance :
* mL/min [acute myocardial infarction patients]

4. Drug Interaction: Targets : Affected organisms :
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.
Targets :
Plasminogen,Fibrinogen alpha chain,Urokinase plasminogen activator surface receptor,Plasminogen activator inhibitor 1,Plasminogen activator inhibitor 2,Tetranectin,Keratin, type II cytoskeletal 8,Annexin A2,Calreticulin,Calnexin,Prolow-density lipoprotein receptor-related protein 1
Affected organisms :
Humans and other mammals .

5. Categories : Patents : Sequence :
Fibrinolytic Agents and Thrombolytic Agents
Patents :
Country Patent Number Approved Expires
Canada
Canada
Sequence :
SYQVICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGGTCQQALYFSDFVCQCPEGFAGKCCEIDTRATCYEDQGISYRGNWSTAESGAECTQWNSSALAQKPYSGRRPDAIRLGLGNHNYCRNPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGSAYRGTHSLTESGASCLPWNSMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCGLRQYSQPQFRIKGGLFADIASHPWQAAAAAKHRRSPGERFLCGGILISSCWILSAAHCFQERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCAQESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQHLLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQKDVPGVYTKVTNYLDWIRDNMRP

6. Brands : TNKase
Company : Genentech Inc
Description : TNKase® is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using an established mammalian cell line (Chinese Hamster Ovary cells). 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. Cell culture is carried out in nutrient medium containing the antibiotic gentamicin (65 mg/L). However, the presence of the antibiotic is not detectable in the final product (limit of detection is 0.67 (µg/vial)
Used for/Prescribed for : used to prevent death from a heart attack (acute myocardial infarction).
Formulation : Each vial of TNKase nominally contains 52.5 mg Tenecteplase, 0.55 g L-arginine, 0.17 g phosphoric acid, and 4.3 mg polysorbate 20, which includes a 5% overfill. Each vial will deliver 50 mg of Tenecteplase.
Form : sterile, white to off-white, lyophilized powder
Route of administration : intravenous injection

7. Dosage : The recommended total dose should not exceed 50 mg and is based upon patient weight. For less than 60 kg of body weight recommended dose is 30 mg of TNKase. Similarly 35 mg for kg, 40 mg for kg, 45 mg for kg and 50 mg for more than 90 kg of body weight. Contraindication : Active internal bleeding, History of cerebrovascular accident, Intracranial or intraspinal surgery or trauma within 2 months . Side effects : chest pain, slow or uneven heartbeats; pain, swelling, hot or cold feeling, skin changes, or discoloration anywhere on your body; sudden leg or foot pain, foot ulcer, purple toes or fingers; Drug interaction : A total of 183 drugs (709 brand and generic names) are known to interact with TNKase (tenecteplase) major drug interactions (79 brand and generic names) moderate drug interactions (624 brand and generic names) minor drug interactions (6 brand and generic names)

8. General references :
# Gurbel PA, Hayes K, Bliden KP, Yoho J, Tantry US: The platelet-related effects of tenecteplase versus alteplase versus reteplase. Blood Coagul Fibrinolysis Jan;16(1):1-7. "Pubmed":
# 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 Aug;18(1): "Pubmed":
# 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 Jul;150(1): "Pubmed":
# 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 Dec;9(4): Epub 2005 Nov 2. "Pubmed":
# : Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial. Lancet Feb 18;367(9510): "Pubmed":

9. References : http://www.drugs.com/mtm/tnkase.html http://www.rxlist.com/tnkase-drug.htm