PAI-1

Synonyms

SERPINE1, PAI-1, PAI1, Serpin Family E Member 1, Serpin E1, PLANH1, PAI, Serpin Peptidase Inhibitor, Clade E (Nexin, Plasminogen Activator Inhibitor Type 1), Member 1, Plasminogen Activator Inhibitor, Type I, Plasminogen Activator Inhibitor 1, Endothelial plasminogen activator inhibitor, Serine (Or Cysteine) Proteinase Inhibitor, Clade E (Nexin, Plasminogen Activator Inhibitor Type 1), Member 1

Description

PAI-1 (plasminogen activator inhibitor-1) is a member of the evolutionarily conserved serine protease inhibitor family and a potent and rapid-acting inhibitor of both of the mammalian plasminogen activators. It is the main regulator of endogenous fibrinolysis, overriding the impact of other constituents of fibrinolysis. In plasma, it can be found in three forms: active, latent and inactive.

KO Status

RenMab: F0

Drug Information

Launched drug: 1
Drug in clinical trials: 1
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Defibrotide sodium

JZP-381

Approved

Jazz Pharmaceuticals, Gentium Srl

Lymphoma, Large B-Cell, Diffuse, Neurotoxicity Syndromes, Hepatic Veno-Occlusive Disease

THR-18

THR-18

Phase 2 Clinical

D-Pharm, Hadassah Medical Organization

Stroke

U-84793

FK-2P, U-84793

Pending

Pfizer Inc

Thrombosis

Aleplasinin

PAZ-417

Discontinued

Pfizer Pharmaceuticals Ltd (China), Wyeth

Alzheimer Disease

Ancrod

Discontinued

Abbvie Inc

Brain Ischemia, Brain Infarction, Deafness, Hearing Loss, Sensorineural, Stroke, Hearing Disorders, Ear Diseases, Hearing Loss

Tiplasinin

PAI-039

Discontinued

Pfizer Pharmaceuticals Ltd (China), Wyeth

Thrombosis

Diaplasinin

PAI-749

Discontinued

Wyeth, Pfizer Inc

Thrombosis

References


Title

Authors

Source

Cloning and sequence of a cDNA coding for the human beta-migrating endothelial-cell-type plasminogen activator inhibitor

Ny T., Sawdey M., Lawrence D., Millan J.L., Loskutoff D.J.,

Proc. Natl. Acad. Sci. U.S.A. 83:6776-6780(1986)

Plasminogen activator inhibitor type-1: reactive center and amino-terminal heterogeneity determined by protein and cDNA sequencing

Andreasen P.A., Riccio A., Welinder K.G., Douglas R., Sartorio R., Nielsen L.S., Oppenheimer C., Blasi F., Danoe K.,

FEBS Lett. 209:213-218(1986)

cDNA cloning and expression in E. coli of a plasminogen activator inhibitor (PAI) related to a PAI produced by Hep G2 hepatoma cell

Wun T.C., Kretzmer K.K.,

FEBS Lett. 210:11-16(1987)

Deficiency of plasma plasminogen activator inhibitor 1 results in hyperfibrinolytic bleeding

Lee M.H., Vosburgh E., Anderson K., McDonagh J.,

Blood 81:2357-2362(1993)

Identification of a PAI-1 binding site in vitronectin

Sigurdardottir O., Wiman B.,

Biochim. Biophys. Acta 1208:104-110(1994)

Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene

Fay W.P., Parker A.C., Condrey L.R., Shapiro A.D.,

Blood 90:204-208(1997)

Structural basis of latency in plasminogen activator inhibitor-1

Mottonen J., Strand A., Symersky J., Sweet R.M., Danley D.E., Geoghegan K.F., Gerard R.D., Goldsmith E.J.,

Nature 355:270-273(1992)

Mechanisms contributing to the conformational and functional flexibility of plasminogen activator inhibitor-1

Aertgeerts K., de Bondt H.L., de Ranter C.J., Declerck P.J.,

Nat. Struct. Biol. 2:891-897(1995)

Interfering with the inhibitory mechanism of serpins: crystal structure of a complex formed between cleaved plasminogen activator inhibitor type 1 and a reactive-centre loop peptide

Xue Y., Bjoerquist P., Inghardt T., Linschoten M., Musil D., Sjoelin L., Deinum J.,

Structure 6:627-636(1998)

The active conformation of plasminogen activator inhibitor 1, a target for drugs to control fibrinolysis and cell adhesion

Sharp A.M., Stein P.E., Pannu N.S., Carrell R.W., Berkenpas M.B., Ginsburg D., Lawrence D.A., Read R.J.,

Structure 7:111-118(1999)