UPA

Synonyms

PLAU, uPA, Plasminogen Activator, Urokinase, Urokinase-Type Plasminogen Activator, Plasminogen Activator, Urinary, BDPLT5, U-PA, ATF, QPD, URK, EC:3.4.21.73, EC 3.4.21, U-Plasminogen Activator, EC 3.4.21.73

Description

Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. Urokinase was originally isolated from human urine, and it is also present in the blood and in the extracellular matrix of many tissues. The primary physiological substrate of this enzyme is plasminogen, which is an inactive form (zymogen) of the serine protease plasmin. Activation of plasmin triggers a proteolytic cascade that, depending on the physiological environment, participates in thrombolysis or extracellular matrix degradation. This cascade had been involved in vascular diseases and cancer progression.

KO Status

F1 (+/-)

Drug Information

Launched drugs: 2
Drugs in clinical trials: 5
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Nasaruplase

GE-0943

Approved

Mitsubishi Pharma Corp

Myocardial Infarction, Venous Thrombosis

Urokinase biosimilar (Bharat Serums & Vaccines)

U-FRAG

Approved

Bharat Serums And Vaccines

Pulmonary Embolism

Upamostat Hydrogen Sulphate

LH-011, WX-671

Phase 3 Clinical

Wilex

Pancreatic Neoplasms, Coronavirus Disease 2019 (COVID-19), Breast Neoplasms, Colorectal Neoplasms

Gallium-68 NOTA AE105 (Curasight)

CS-001, 68Ga-NOTA-AE105

Phase 2 Clinical

Curasight

Head and Neck Neoplasms, Glioblastoma, Neuroendocrine Tumors, Mesothelioma, Urinary Bladder Neoplasms, Breast Neoplasms, Prostatic Neoplasms, Oropharyngeal Neoplasms, Genital Neoplasms, Female, Carcinoma, Non-Small-Cell Lung

Angstrom6

A6

Phase 2 Clinical

Angstrom

Ovarian Neoplasms, Peritoneal Neoplasms, Leukemia, Lymphocytic, Chronic, B-Cell

tPA/HisproUK (Thrombolytic Science)

TS-01

Phase 2 Clinical

Thrombolytic Science

Stroke

Recombinant human annexin 5 protein (Yabao Pharmaceuticals)

SY-005

Phase 1 Clinical

Lawson Health Research Institute, Yabao Pharmaceutical Group Co Ltd

Sepsis

IPR-1110

IPR 1110

Preclinical

Neoplasms

Recombinant staphylokinase-hirudin fusion protein

Pending

Institute Of Radiological Medicine, Chinese Academy Of Military Medical Sciences, Humanwell Healthcare (Group) Co Ltd

Thromboembolism

UK-356202

UK-356202

Discontinued

Pfizer Inc

Vascular Diseases, Skin Ulcer, Neoplasm Metastasis

References


Title

Authors

Source

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)

The MGC Project Team,

Genome Res. 14:2121-2127(2004)

Characterization of single chain urokinase-type plasminogen activator with a novel amino-acid substitution in the kringle structure

Yoshimoto M., Ushiyama Y., Sakai M., Tamaki S., Hara H., Takahashi K., Sawasaki Y., Hanada K.,

Biochim. Biophys. Acta 1293:83-89(1996)

Characterization of a posttranslational fucosylation in the growth factor domain of urinary plasminogen activator

Buko A.M., Kentzer E.J., Petros A., Menon G., Zuiderweg E.R., Sarin V.K.,

Proc. Natl. Acad. Sci. U.S.A. 88:3992-3996(1991)

Identification and primary sequence of an unspliced human urokinase poly(A)+ RNA

Verde P., Stoppelli M.P., Galeffi P., di Nocera P., Blasi F.,

Proc. Natl. Acad. Sci. U.S.A. 81:4727-4731(1984)

The primary structure of high molecular mass urokinase from human urine. The complete amino acid sequence of the A chain

Gunzler W.A., Steffens G.J., Otting F., Kim S.-M.A., Frankus E., Flohe L.,

Hoppe-Seyler's Z. Physiol. Chem. 363:1155-1165(1982)

Human low-molecular-weight urinary urokinase. Partial characterization and preliminary sequence data of the two polypeptide chains

Schaller J., Nick H., Rickli E.E., Gillessen D., Lergier W., Studer R.O.,

Eur. J. Biochem. 125:251-257(1982)

The complete amino acid sequence of low molecular mass urokinase from human urine

Steffens G.J., Gunzler W.A., Otting F., Frankus E., Flohe L.,

Hoppe-Seyler's Z. Physiol. Chem. 363:1043-1058(1982)

Inhibition of urokinase by protein C-inhibitor (PCI). Evidence for identity of PCI and plasminogen activator inhibitor 3

Stief T.W., Radtke K.P., Heimburger N.,

Biol. Chem. Hoppe-Seyler 368:1427-1433(1987)

Phosphorylation of human pro-urokinase on Ser138/303 impairs its receptor-dependent ability to promote myelomonocytic adherence and motility

Franco P., Iaccarino C., Chiaradonna F., Brandazza A., Iavarone C., Mastronicola M.R., Nolli M.L., Stoppelli M.P.,

J. Cell Biol. 137:779-791(1997)

Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility

He S., Lin Y.L., Liu Y.X.,

Mol. Hum. Reprod. 5:513-519(1999)