| Identification | Back Directory | [Name]
Urokinase | [CAS]
9039-53-6 | [Synonyms]
uk
tcuk
e-PPA
Uronase
win22005
UROKINASE
win-kinase
urokinaase
Abblihinase
EC 3.4.99.26
e.c.3.4.21.31
HUMANUROKINASE
UROKINASE, SCU-PA
UROKINASE 2-CHAIN
UROKINASE (MIXED)
UROKINASE UPA 2-CHAIN
tissuecultureurokinase
Urokinase froM huMan ur
u-Plasminogen activator
Human Urokinase-hUK
UROKINASE, LOW MW (URINE)
UROKINASE, HIGH MW (URINE)
UROKINASE FROM HUMAN URINE
uro-kinase(enzyme-activating
Kinase (enzyme-activating), uro-
UROKINASE, PLASMINOGEN ACTIVATOR
UROKINASE, HIGH MOLECULAR WEIGHT
urokinase from human kidney cells
UROKINASE STERILE FROM HUMAN URINE
UROKINASE, PLASMINOGEN ACTIVATOR, LOW MOLECULAR WEIGHT | [EINECS(EC#)]
232-917-9 | [Molecular Formula]
C21H25BrN2O3 | [MDL Number]
MFCD00132566 |
| Chemical Properties | Back Directory | [Appearance]
White or almost white, amorphous powder. | [storage temp. ]
2-8°C
| [solubility ]
Soluble in water. | [form ]
powder
| [color ]
white
| [Water Solubility ]
Reconstitute in water at 100µg/ml | [Uses]
The effect of systemic administration of urokinase is unclear. One study reported the effectiveness of superselective ophthalmic artery fibrinolytic therapy of urokinase for CRVO. Urokinase was infused through a microcatheter into the ostium of the ophthalmic artery via the femoral artery. Six eyes of 26 patients had a significant improvement in VA 24 hours after the fibrinolysis; eyes with combined central retinal artery occlusion and CRVO with recent visual impairment appeared to be the most responsive. | [CAS DataBase Reference]
9039-53-6 | [EPA Substance Registry System]
Kinase (enzyme-activating), uro-(9039-53-6) |
| Safety Data | Back Directory | [Hazard Codes ]
B | [WGK Germany ]
3
| [RTECS ]
OB8900000
| [F ]
10-21 | [TSCA ]
Yes | [Safety Profile]
An experimental
teratogen. Experimental reproductive
effects. Used in the treatment of diseases
caused by blood clots. |
| Hazard Information | Back Directory | [Description]
Urokinase is an enzyme that is extracted from human urine or kidney cells, which directly cleaves specific peptide bonds, in particular the Arg-560–Val-561
bond in the plasminogen molecule, thus transforming it into plasmin. | [Chemical Properties]
White or almost white, amorphous powder. | [Originator]
Abbofinase,Abbott,UK,1962 | [Manufacturing Process]
In 20 liters of human urine is dissolved 1,200 grams of sodium benzoate (6%
weight by volume). The solution is acidified with aqueous hydrochloric acid
(assay about 7.5% HCl) to a pH of 4.5 resulting in a heavy precipitation. This
requires 10% of the original urine volume, or about 2 liters of aqueous
hydrochloric acid. The suspension is stirred 20 minutes and is then allowed to
stand for about 30 minutes. The mixture so obtained is filtered on a Buchner
funnel that has been prepared with a precoat of benzoic acid crystals over
filter paper. The filter cake is washed with a saturated benzoic acid solution,
then sucked dry. The benzoic acid cake with the adsorbed urokinase weighs
2,060 grams.
The filter cake is stirred with 3.1 liters of acetone. The volume of acetone
used is about 1.5 times the weight of the cake resulting in about a 65%
acetone concentration. The benzoic acid dissolves in the acetone and the
urokinase flocculates out. Sodium benzoate, about 1% of the weight of the
cake, or 21 grams, is added to speed up the formation of the precipitate. The
suspension of crude urokinase in acetone is filtered on a Buchner funnel using
filter paper precoated with a diatomaceous silica product (Celite 505). The
precipitate is washed with acetone until the filtrate is water clear. The
precipitate is then washed with ether and air dried. The yield of powder so
obtained is 2.3 grams.
Four batches of urokinase, obtained in this manner from 202 liters of urine, is
pooled, amounting to 23.5 grams. The combined urokinase is suspended in 750 ml of 0.1 M phosphate-saline buffer at pH 6.2, stirred to dissolve the
urokinase and centrifuged to remove the Celite. The residue is extracted two
more times with 500 ml portions of 0.1 M phosphate-saline buffer. The
combined extracts are filtered and labelled Extract 1.The residue is extracted
three more times with 600 ml portions of buffer, the combined extracts are
filtered and labelled Extract 2.
The clarified solution of the first phosphate-saline buffer extract, 1,320 ml, is
passed through 110 cm of Amberlite XE-64 ion exchange resin contained in a
column 10 cm in diameter. The resin exchange column has a hold-up volume
of about 2.8 liters. The second extract (Extract 2) of the Celite residue, 1,720
ml, is then passed through the same exchange column. The column is washed
with 11.4 liters of the phosphate-saline buffer. Then the adsorbate is eluted
with 9 liters of 0.5 M sodium chloride. The eluate is dialyzed through a viscose
regenerated cellulose membrane against distilled water. The active fractions
within the dialysis sacs, totaling 4,940 ml, are pooled and lyophilized. The
yield is 2.5 grams having an activity of 415,000 units or 166 units per milligram. | [Brand name]
Abbokinase (Imarx). | [Therapeutic Function]
Anticoagulant | [General Description]
Urokinase (Abbokinase) is a glycosylatedserine protease consisting of 411 amino acid residues,which exists as two polypeptide chains connected by a singledisulfide bond. It is isolated from human urine or tissueculture of human kidneys. The only known substrate ofurokinase is plasminogen, which is activated to plasmin, afibrinolytic enzyme. Unlike streptokinase, urokinase is adirect activator of plasminogen. Urokinase is nonantigenicbecause it is an endogenous enzyme and, therefore, may beused when streptokinase use is impossible because of antibodyformation. It is administered intravenously or by theintracoronary route. Its indications are similar to those ofstreptokinase. | [Biochem/physiol Actions]
Urokinase expression and invasiveness suppression by urinary trypsin inhibitor acts through MEK/ERK/c-Jun-dependent signaling pathways. | [Mechanism of action]
Urokinase is an enzyme with the ability to directly degrade fibrin and fibrinogen. It is now isolated
from cultures of human fetal kidney cells and is composed of two polypeptide chains with molecular
weights of 32 and 54 kDa. | [Pharmacokinetics]
This method of isolation is much more efficient than the original isolation
of urokinase from human urine. Because of its source, the human body does not see urokinase
as a foreign protein. Therefore, it lacks the antigenicity associated with streptokinase and
frequently is used for patients with a known hypersensitivity to streptokinase. Plasmin cannot
be used directly because of the presence of naturally occurring plasmin antagonists in plasma. No
such inhibitors of urokinase exist in the plasma, however, allowing this enzyme to have clinical
utility. Even so, urokinase is much more expensive (threefold the price of streptokinase) and has an
even shorter half-life (15 minutes). Urokinase also has other fibrin-nonspecific actions similar to
streptokinase. | [Clinical Use]
Fibrinolytic agent:
Thrombosed arteriovenous shunts and intravenous cannulas
Treatment of thromboembolic occlusive vascular disease, e.g. DVT, PE, peripheral vascular occlusion | [Drug interactions]
Potentially hazardous interactions with other drugs
None known | [Metabolism]
Urokinase is eliminated rapidly from the circulation by
the liver.
The inactive degradation products are excreted mainly via
the kidneys and also the bile. | [Purification Methods]
Crystallisation of this enzyme is induced at pH 5.0 to 5.3 (4o) by careful addition of NaCl with gentle stirring until the solution becomes turbid (silky sheen). The NaCl concentration is increased gradually (over several days) until 98% of saturation is achieved whereby urokinase crystallises out as colourless thin brittle plates. It can be similarly recrystallised to maximum specific activity [104K CTA units/mg of protein (Sherry et al. J Lab Clin Med 64 145 1964)]. [Lesuk et al. Science 147 880 1965, NMR: Bogusky et al. Biochemistry 28 6728 1989.] Itisa plasminogen activator [Gold et al. Biochem J 262 1989, de Bock & Wang Med Res Rev 24(1) 13 2004]. |
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