STREPTOKINASE

STREPTOKINASE Basic information
Product Name:STREPTOKINASE
Synonyms:awelysin;kabikinase;streptase;streptococcalfibrinolysin;strepto-kinase(enzyme-activating;Dickkopf-1;Dickkopf-related protein-1;DKK-1 human
CAS:9002-01-1
MF:C11H19NO2
MW:197.27406
EINECS:232-647-1
Product Categories:enzyme;Streptokinase Bulk Solution;Crude Streptokinase;Refined Streptokinase
Mol File:9002-01-1.mol
STREPTOKINASE Structure
STREPTOKINASE Chemical Properties
storage temp. -20°C
form lyophilized powder
Merck 13,8903
Safety Information
Hazard Codes B,Xi
Risk Statements 36/37/38
Safety Statements 22-24/25-36-26
WGK Germany 3
RTECS OB8880000
10-21
HS Code 3504009000
ToxicityLD50 oral in mouse: > 10gm/kg
MSDS Information
ProviderLanguage
SigmaAldrich English
STREPTOKINASE Usage And Synthesis
DescriptionStreptokinase is a protein produced by certain strains of hemolytic group C streptococcus, and it was the first clinically useful fibrinolytic. Unlike other plasminogen activators, streptokinase is not an enzyme and cannot break any bonds in a plasminogen molecule by itself. It forms an equimolecular compound with plasminogen, thus forming a streptokinase–plasminogen complex. In the plasminogenic region of the resulting complex, certain conformational changes lead to a break in a few peptide bonds, and transformation of this complex into a streptokinase–plasmin complex, or free plasmin, which also decomposes fibrin.
OriginatorStreptase,Hoechst,France,1970
UsesThis drug has a half-life in the plasma of 15–30 min, and is used intravenously to treat patients with severe, massive pulmonary embolism and thrombus of the veins; it is also used during myocardial infarctions. Recently, a number of streptokinase derivatives have been proposed, in particular acetylated derivatives, which are developed for use as fibrinolytics.
UsesStreptokinase is commonly used as a thrombolytic agent in the therapy of ischemic stroke. This therapy carries the important risk of intracerebral hemorrhage. Streptokinase is also used in the treatment of complicated parapneumonic effusions and empyema where adverse reactions, allergic type, are rare. Streptokinase has been used in a study to compare primary coronary intervention and thrombolytic therapy in myocardial infarction patients.
Therapeutic FunctionEnzyme
General DescriptionStreptokinase (Kabikinase, Streptase)is a catabolic 47,000-d protein secreted by group Cβ-hemolyticstreptococci. It is a protein with no intrinsic enzymaticactivity. Streptokinase activates plasminogen toplasmin, a proteolytic enzyme that hydrolyzes fibrin andpromotes the dissolution of thrombi. Plasminogen is activatedwhen streptokinase forms a 1:1 stoichiometric complexwith it. Allergic reactions to streptokinase occur commonlybecause of antibody formation in individuals treatedwith it. Furthermore, the antibodies inactivate streptokinaseand reduce its ability to prolong thrombin time.Streptokinase is indicated for acute myocardial infarction,for local perfusion of an occluded vessel, and before angiography,by intravenous, intra-arterial, and intracoronaryadministration, respectively.
Biochem/physiol ActionsDKK1 (dickkopf WNT signaling pathway inhibitor 1) functions as a pure inhibitor of Wnt signaling, and was identified as an essential factor for head induction during early Xenopus embryogenesis by suppressing Wnt signaling. In skin, this protein plays a role in determining the pigmentation pattern of the human hand. In colon cancer cells, this protein is inactivated by CpG island promoter hypermethylation. Mesenchymal stem cells (MSCs) have an anti-proliferative effect on cancer cells, as they secrete DKK1 which blocks Wnt signaling.
Mechanism of actionStreptokinase is a protein purified from culture broths of group C β-hemolytic streptococci bacteria. Streptokinase contains a single polypeptide chain of 414-amino-acid residues with a molecular weight of 47 kDa. Streptokinase by itself has no intrinsic enzymatic activity. To be active, it must bind with plasminogen to form an activator complex (1:1 complex). This complex then acts to convert uncomplexed plasminogen to the active fibrinolytic enzyme, plasmin. The streptokinase/plasminogen complex not only degrades fibrin clots but also catalyzes the breakdown of fibrinogen and factors V and VII. As a result, streptokinase is considered to be a fibrinnonspecific drug.
PharmacokineticsUnfortunately, the half-life of the activator complex is less than 30 minutes, which frequently is too short to completely lyse a thrombus. Anistreplase (APSAC; Eminase) is a 1:1 streptokinase/lysineplasminogen complex that has been acylated with an anisoyl group at the active-site serine within the lysine-plasminogen. Anistreplase is inactive as such, but following complexation with fibrin, the anisoyl group is slowly cleaved, exposing the active site and, thus, leading to degradation of fibrin. The pro-drug nature of anistreplase exhibits an improved pharmacokinetic profile, with anistreplase acting as a semiselective lysis agent at the clot site. The inactivity of the circulating anistreplase also allows this drug to be given as a very rapid intravenous infusion (typically, 30 U over 3–5 minutes). Tissue reperfusion following anistreplase therapy compares favorably to streptokinase because of the extended half-life (90 minutes).
Clinical UseFibrinolytic:
Thrombolysis in DVT, PE, acute arterial thromboembolism, acute MI, thrombosed A-V shunts
Side effectsBecause it is a foreign protein, streptokinase is associated with significant hypersensitivity reactions. Most people have, at some point in their lives, had a streptococcal infection and, therefore, have developed circulating antistreptococcal antibodies. These antibodies frequently are active against streptokinase as well. The response of the streptokinase to these antibodies can vary widely, from inactivation of the fibrinolytic properties of the protein to rash, fever, and rarely, anaphylaxis. Significant allergic reactions to streptokinase occur in approximately 3% of patients.
Veterinary Drugs and TreatmentsStreptokinase may be useful for the adjunctive treatment of serious thromboses. The use of thrombolytics (streptokinase, t-PA) in cats is controversial.
Drug interactionsPotentially hazardous interactions with other drugs
Anticoagulants should not be given with streptokinase.
Heparin infusions should be stopped 4 hours before streptokinase infusion. If this is not possible, protamine sulphate should be used to neutralise the heparin; heparin infusions can be restarted 4 hours post streptokinase infusion followed by oral anticoagulants.

MetabolismA small proportion of the dose is bound to antistreptokinase antibodies and metabolised with a half-life of 18 minutes, whilst most of it forms the streptokinaseplasminogen activator complex and is biotransformed with a half-life of about 80 minutes.
STREPTOKINASE Preparation Products And Raw materials
Raw materialsCalcium phosphate-->Cholesterol
Preparation ProductsStreptodornase/streptokinase
Aluminum acetylacetonate METHYL ISOCYANOACETATE N-BUTYLISOCYANIDE PHENYLSELENOL Tris(2,4-pentanedionato)chroMiuM(III) DICHLORO(ETHYLENEDIAMINE)PLATINUM(II) SALCOMINE 2,4-PENTANEDIONE, SILVER DERIVATIVE 1,1,3,3-TETRAMETHYLBUTYL ISOCYANIDE Tosylmethyl isocyanide COBALT(II) ACETYLACETONATE Cupric acetylacetonate Ethyl isocyanoacetate TERT-BUTYL ISOCYANIDE Ferric acetylacetonate COBALT ETHYLENE DIAMINE CHLORIDE Benzyl isocyanide TRIS(2,2,6,6-TETRAMETHYL-3,5-HEPTANEDIONATO)DYSPROSIUM(III)

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