Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTTO43N)

• DTT Name: Endothelial plasminogen activator inhibitor (SERPINE1)
• Synonyms: Serpin E1; Plasminogen activator inhibitor type 1; Plasminogen activator inhibitor 1; PLANH1; PAI1; PAI-1
• Gene Name: SERPINE1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Serpin protein
• UniProt ID: PAI1_HUMAN
• TTD ID: T15556
• Sequence:
  MQMSPALTCLVLGLALVFGEGSAVHHPPSYVAHLASDFGVRVFQQVAQASKDRNVVFSPY
  GVASVLAMLQLTTGGETQQQIQAAMGFKIDDKGMAPALRHLYKELMGPWNKDEISTTDAI
  FVQRDLKLVQGFMPHFFRLFRSTVKQVDFSEVERARFIINDWVKTHTKGMISNLLGKGAV
  DQLTRLVLVNALYFNGQWKTPFPDSSTHRRLFHKSDGSTVSVPMMAQTNKFNYTEFTTPD
  GHYYDILELPYHGDTLSMFIAAPYEKEVPLSALTNILSAQLISHWKGNMTRLPRLLVLPK
  FSLETEVDLRKPLENLGMTDMFRQFQADFTSLSDQEPLHVAQALQKVKIEVNESGTVASS
  STAVIVSARMAPEEIIMDRPFLFVVRHNPTGTVLFMGQVMEP
• Function: Inhibits TMPRSS7. Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots. As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading. Acts as a regulator of cell migration, independently of its role as protease inhibitor. It is required for stimulation of keratinocyte migration during cutaneous injury repair. It is involved in cellular and replicative senescence. Plays a role in alveolar type 2 cells senescence in the lung. Is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells, and regulates odontoblast differentiation and dentin formation during odontogenesis. Serine protease inhibitor.
• KEGG Pathway:
  HIF-1 signaling pathway (hsa04066)
  p53 signaling pathway (hsa04115)
  Hippo signaling pathway (hsa04390)
  Complement and coagulation cascades (hsa04610)
  Chagas disease (American trypanosomiasis) (hsa05142)
• Reactome Pathway:
  BMAL1 (R-HSA-1368108)
  SMAD2/SMAD3 (R-HSA-2173796)
  ECM proteoglycans (R-HSA-3000178)
  Dissolution of Fibrin Clot (R-HSA-75205)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
THR-18	DMBO021	Asthma	CA23	Phase 2	[1]
DIAPLASININ	DM6OJI1	Thrombosis	DB61-GB90	Phase 1	[2]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
XR-5118	DMIK72F	Solid tumour/cancer	2A00-2F9Z	Terminated	[3]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AR-HO29953XX	DM2PRHX	Discovery agent	N.A.	Investigative	[4]
SIDEROXYLONAL A	DMEIBTY	Discovery agent	N.A.	Investigative	[5]
SIDEROXYLONAL B	DMDP7Y5	Discovery agent	N.A.	Investigative	[5]
Sideroxylonal C	DMSGNM1	Discovery agent	N.A.	Investigative	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	1.56E-01	0.05	0.14

References

• [1] THR-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.
• [2] Effect 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.
• [3] Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: design, synthesis, and preclinical characterization. J Med Chem. 2004 Jul 1;47(14):3491-4.
• [4] Synthesis and SAR of 2-carboxylic acid indoles as inhibitors of plasminogen activator inhibitor-1. Bioorg Med Chem Lett. 2005 Aug 1;15(15):3514-8.
• [5] Sideroxylonal C, a new inhibitor of human plasminogen activator inhibitor type-1, from the flowers of Eucalyptus albens. J Nat Prod. 1999 Feb;62(2):324-6.