Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT5QA2I)

• DTT Name: Plasminogen activator inhibitor (PAI)
• Synonyms: Serpin; PAI
• Gene Name: SERPINE1
• DTT Type: Clinical trial target; [1]
• UniProt ID: PAI1_HUMAN ; PAI2_HUMAN ; IPSP_HUMAN
• TTD ID: T45151
• Sequence:
  MQMSPALTCLVLGLALVFGEGSAVHHPPSYVAHLASDFGVRVFQQVAQASKDRNVVFSPY
  GVASVLAMLQLTTGGETQQQIQAAMGFKIDDKGMAPALRHLYKELMGPWNKDEISTTDAI
  FVQRDLKLVQGFMPHFFRLFRSTVKQVDFSEVERARFIINDWVKTHTKGMISNLLGKGAV
  DQLTRLVLVNALYFNGQWKTPFPDSSTHRRLFHKSDGSTVSVPMMAQTNKFNYTEFTTPD
  GHYYDILELPYHGDTLSMFIAAPYEKEVPLSALTNILSAQLISHWKGNMTRLPRLLVLPK
  FSLETEVDLRKPLENLGMTDMFRQFQADFTSLSDQEPLHVAQALQKVKIEVNESGTVASS
  STAVIVSARMAPEEIIMDRPFLFVVRHNPTGTVLFMGQVMEP
• 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 offibrinolysis.
• 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

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aleplasinin	DMYTIP4	Alzheimer disease	8A20	Phase 1	[1]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BX-044	DM0P8CE	Thrombosis	DB61-GB90	Terminated	[2]
T-686	DMOGQ2L	Arteriosclerosis	BD40	Terminated	[3]
XR-1853	DMFHR2O	Thrombosis	DB61-GB90	Terminated	[4]
XR-5082	DMEVSZO	Thrombosis	DB61-GB90	Terminated	[5]

References

• [1] CN patent application no. 102046168, Pai-1 expression and activity inhibitors for the treatment of ocular disorders.
• [2] Characterization of a small molecule PAI-1 inhibitor, ZK4044. Thromb Res. 2005;115(4):341-50.
• [3] T-686, a novel inhibitor of plasminogen activator inhibitor-1, inhibits thrombosis without impairment of hemostasis in rats. Eur J Pharmacol. 1997 Jul 9;330(2-3):151-6.
• [4] Characterization and comparative evaluation of a novel PAI-1 inhibitor. Thromb Haemost. 2002 Jul;88(1):137-43.
• [5] Evaluation of a low molecular weight modulator of human plasminogen activator inhibitor-1 activity. Thromb Haemost. 1996 May;75(5):808-15.