From Wikipedia, the free encyclopedia
Jump to: navigation, search
Systematic (IUPAC) name
Human tissue plasminogen activator
Clinical data
Trade names Tnkase
AHFS/Drugs.com monograph
Legal status
  • Prescription only
Pharmacokinetic data
Excretion Liver
CAS number 105857-23-6 YesY
ATC code B01AD11
DrugBank DB00031
KEGG D02837 YesY
Chemical data
Formula C2561H3919N747O781S40 
Mol. mass 58951.2 g/mol
 YesY (what is this?)  (verify)

Tenecteplase (TNK) is an enzyme used as a thrombolytic drug.

Tenecteplase 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.

Tenecteplase is a recombinant fibrin-specific plasminogen activator that is derived from native t-PA by modifications at three sites of the protein structure. It binds to the fibrin component of the thrombus (blood clot) and selectively converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus. Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor (PAI-1) compared to native t-PA.


Researchers at Newcastle University in Australia say they have had a significant breakthrough in treating stroke patients using the commonly used drug. The findings were published in the New England Medical Journal. There is ongoing controversy about whether this is a harmful treatment, and significant ongoing discussion between Emergency Physicians and Neurologists about whether this treatment should be used at all.


Distribution: approximates plasma volume

Metabolism: Primarily hepatic

Half-life elimination: Biphasic: Initial: 20-24 minutes; Terminal: 90-130 minutes

Excretion: Clearance: Plasma: 99-119 mL/minute


Here is TNK-tPA. It is very similar to t-PA, but the glycosylation occurring in Kringle 1 is manipulated. The mutation T103N means that glycosylation occurs at that point. The mutation N117E means that the high mannose sugar residue is absent at that point.
In human t-PA, the amino acids at position 296-299 are Lysine, Histidine, and two Arginines.
In TNK-tPA, these amino acids have been replaced by four Alanines. This mutation is responsible for increased resistance to PAI-1.

External links[edit]