Tenecteplase, sold under the trade names TNKase, Metalyse and Elaxim, is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

used as a

thrombolytic drug Thrombolysis, also called fibrinolytic therapy, is the breakdown ( lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massiv ...

. Tenecteplase is a

tissue plasminogen activator Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein involved in the breakdown of blood clots. It is a serine protease () found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion ...

(tPA) produced by

recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be foun ...

technology using an established mammalian cell line ( Chinese hamster ovary cells). Tenecteplase is a 527 amino acid

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

developed by introducing the following modifications to the

complementary DNA In genetics, complementary DNA (cDNA) is DNA synthesized from a single-stranded RNA (e.g., messenger RNA (mRNA) or microRNA (miRNA)) template in a reaction catalyzed by the enzyme reverse transcriptase. cDNA is often used to express a spe ...

for natural human tPA: a substitution of

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO� ...

103 with

asparagine Asparagine (symbol Asn or N) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the depro ...

, and a substitution of asparagine 117 with

glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, ...

, 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 Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with platele ...

-specific

plasminogen Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encode ...

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 A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of c ...

(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 Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor or serpin E1 is a protein that in humans is encoded by the ''SERPINE1'' gene. Elevated PAI-1 is a risk factor for thrombosis and atherosclerosis P ...

) compared to native t-PA. The abbreviation TNK is common for referring to tenecteplase, but abbreviating drug names is not

best practice A best practice is a method or technique that has been generally accepted as superior to other known alternatives because it often produces results that are superior to those achieved by other means or because it has become a standard way of doing ...

in medicine, and in fact "TNK" is one of the examples given on the

Institute for Safe Medication Practices The Institute for Safe Medication Practices (ISMP) is an American 501(c)(3) organization focusing on the prevention of medication errors and promoting safe medication practices. It is affiliated with the ECRI Institute ECRI (originally founded ...

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. Though safety has been established through previous clinical trials, there is ongoing debate about whether this is an effective treatment for

ischemic stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

, and significant ongoing discussion between emergency physicians, neurologists and pharmacists about whether this treatment should be used for that indication. The

American Heart Association The American Heart Association (AHA) is a nonprofit organization in the United States that funds cardiovascular medical research, educates consumers on healthy living and fosters appropriate cardiac care in an effort to reduce disability and death ...

/American Stroke Association 2019 update to the 2018 guidelines for the Early Management of Acute Ischemic Stroke supports considering tenecteplase over

alteplase Alteplase (t-PA), a biosynthetic form of human tissue-type plasminogen activator (t-PA), is a thrombolytic medication, used to treat acute ischemic stroke, acute ST elevation myocardial infarction, ST-elevation myocardial infarction (a type of h ...

in patients without contraindication to intravenous thrombolytics.

Pharmacokinetics

Distribution: approximates

plasma volume Blood volume (volemia) is the volume of blood (blood cells and plasma) in the circulatory system of any individual. Humans A typical adult has a blood volume of approximately 5 liters, with females and males having approximately the same blood per ...

Metabolism: Primarily hepatic Half-life elimination: Biphasic: Initial: 20–24 minutes; Terminal: 90–130 minutes Excretion: Clearance: Plasma: 99-119 mL/minute

Gallery

References

External links

* {{Antithrombotics Antithrombotic enzymes Hoffmann-La Roche brands Genentech brands

Research

Pharmacokinetics

Gallery

References

Further reading

External links