Tenecteplase

Tenecteplase

Systematic (IUPAC) name
Human tissue plasminogen activator
Clinical data
Trade names	TNKase
AHFS/Drugs.com	monograph
Legal status	℞ (Prescription only)
Pharmacokinetic data
Excretion	Liver
Identifiers
CAS Number	105857-23-6 Y
ATC code	B01AD11 (WHO)
DrugBank	DB00031 Y
UNII	WGD229O42W Y
KEGG	D02837 Y
Chemical data
Formula	C2561H3919N747O781S40
Molecular mass	58951.2 g/mol
(verify)

Tenecteplase (INN) (trade name TNKase) 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.

The abbreviation TNK is common for referring to tenecteplase, but abbreviating drug names is not best practice in medicine, and in fact "TNK" is one of the examples given on the Institute for Safe Medication Practices (ISMP) do-not-use list.

Research

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.

Pharmacokinetics

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

Gallery

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 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 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. In TNK-tPA, these amino acids have been replaced by four Alanines. This mutation is responsible for increased resistance to PAI-1.

Further reading

• http://www.abc.net.au/news/2012-03-22/stroke-study-makes-treatment-breakthrough/3905512

External links

• MedlinePlus DrugInfo uspdi-500145