Target Information

Target General Infomation
Target ID
T15556
Former ID
TTDR00556
Target Name
Plasminogen activator inhibitor-1
Gene Name
SERPINE1
Synonyms
Endothelial plasminogen activator inhibitor; PAI; PAI-1; Plasminogen activator inhibitor type 1; SERPINE1
Target Type
Clinical Trial
Disease Asthma [ICD10: J45]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Thrombolysis [ICD9: 410, 415.1, 434.91, 459.9; ICD10: I21-I22, I26, I61-I63, I99.9]
Function
Serine protease inhibitor. This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, protein C and matriptase-3/TMPRSS7. Its rapid interaction with PLAT may function as a major control point in the regulation of fibrinolysis.
BioChemical Class
Serpin family
Target Validation
T15556
UniProt ID
P05121
Sequence
MQMSPALTCLVLGLALVFGEGSAVHHPPSYVAHLASDFGVRVFQQVAQASKDRNVVFSPY
GVASVLAMLQLTTGGETQQQIQAAMGFKIDDKGMAPALRHLYKELMGPWNKDEISTTDAI
FVQRDLKLVQGFMPHFFRLFRSTVKQVDFSEVERARFIINDWVKTHTKGMISNLLGKGAV
DQLTRLVLVNALYFNGQWKTPFPDSSTHRRLFHKSDGSTVSVPMMAQTNKFNYTEFTTPD
GHYYDILELPYHGDTLSMFIAAPYEKEVPLSALTNILSAQLISHWKGNMTRLPRLLVLPK
FSLETEVDLRKPLENLGMTDMFRQFQADFTSLSDQEPLHVAQALQKVKIEVNESGTVASS
STAVIVSARMAPEEIIMDRPFLFVVRHNPTGTVLFMGQVMEP
Drugs and Mode of Action
Drug(s) THR-18 Drug Info Phase 2 Asthma [525337]
DIAPLASININ Drug Info Phase 1 Thrombolysis [530810]
XR-5118 Drug Info Terminated Cancer [546207]
Inhibitor AR-HO29953XX Drug Info [527611]
DIAPLASININ Drug Info [530810], [531635]
SIDEROXYLONAL A Drug Info [525438]
SIDEROXYLONAL B Drug Info [525438]
Sideroxylonal C Drug Info [525438]
XR-5118 Drug Info [527117]
Activator THR-18 Drug Info [531696]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway HIF-1 signaling pathway
p53 signaling pathway
Hippo signaling pathway
Complement and coagulation cascades
Chagas disease (American trypanosomiasis)
NetPath Pathway TWEAK Signaling Pathway
IL2 Signaling Pathway
TGF_beta_Receptor Signaling Pathway
PANTHER Pathway Blood coagulation
Plasminogen activating cascade
p53 pathway
CCKR signaling map ST
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling
p73 transcription factor network
E2F transcription factor network
HIF-2-alpha transcription factor network
Direct p53 effectors
Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
HIF-1-alpha transcription factor network
Reactome Platelet degranulation
CLOCK,NPAS2 activates circadian gene expression
SMAD4 heterotrimer regulates transcription
ECM proteoglycans
Dissolution of Fibrin Clot
WikiPathways Senescence and Autophagy in Cancer
TGF Beta Signaling Pathway
Complement and Coagulation Cascades
SMAD4 heterotrimer
Blood Clotting Cascade
Extracellular matrix organization
Oncostatin M Signaling Pathway
Adipogenesis
Dissolution of Fibrin Clot
Circadian Clock
Folate Metabolism
Vitamin B12 Metabolism
Selenium Micronutrient Network
References
Ref 525337ClinicalTrials.gov (NCT02572336) A Study of the Safety, Imaging and Clinical Outcomes of THR-18 in Acute Stroke Subjects Treated With tPA.
Ref 530810Effect of the small molecule plasminogen activator inhibitor-1 (PAI-1) inhibitor, PAI-749, in clinical models of fibrinolysis. J Thromb Haemost. 2010 Jun;8(6):1333-9.
Ref 546207Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006898)
Ref 525438J Nat Prod. 1999 Feb;62(2):324-6.Sideroxylonal C, a new inhibitor of human plasminogen activator inhibitor type-1, from the flowers of Eucalyptus albens.
Ref 527117J Med Chem. 2004 Jul 1;47(14):3491-4.Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: design, synthesis, and preclinical characterization.
Ref 527611Bioorg Med Chem Lett. 2005 Aug 1;15(15):3514-8.Synthesis and SAR of 2-carboxylic acid indoles as inhibitors of plasminogen activator inhibitor-1.
Ref 530810Effect of the small molecule plasminogen activator inhibitor-1 (PAI-1) inhibitor, PAI-749, in clinical models of fibrinolysis. J Thromb Haemost. 2010 Jun;8(6):1333-9.
Ref 531635Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
Ref 531696THR-18, a 18-mer peptide derived from PAI-1, is neuroprotective and improves thrombolysis by tPA in rat stroke models. Neurol Res. 2011 Nov;33(9):983-90.

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