Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Tissue-type plasminogen activator (PLAT)
• Synonyms: TPA; T-plasminogen activator; T-PA; Reteplase; Alteplase
• Gene Name: PLAT
• DTT Type: Successful target; [1]
• BioChemical Class: Peptidase
• UniProt ID: TPA_HUMAN
• TTD ID: T45299
• EC Number: EC 3.4.21.68
• Sequence:
  MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVICRDEKTQMIYQQHQSWLRPV
  LRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGGTCQQALYFSDFVCQCPEGFAGKCCE
  IDTRATCYEDQGISYRGTWSTAESGAECTNWNSSALAQKPYSGRRPDAIRLGLGNHNYCR
  NPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGSAYRGTHSLTESGASCLPWN
  SMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCG
  LRQYSQPQFRIKGGLFADIASHPWQAAIFAKHRRSPGERFLCGGILISSCWILSAAHCFQ
  ERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCA
  QESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQH
  LLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQK
  DVPGVYTKVTNYLDWIRDNMRP
• Function: By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. Plays a direct role in facilitating neuronal migration. Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Transcriptional misregulation in cancer (hsa05202)
• Reactome Pathway: Dissolution of Fibrin Clot (R-HSA-75205)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminocaproic Acid	DMFGND4	Bleeding disorder	GA20-GA21	Approved	[1]

8 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-guanidino-N-phenyl-7-isoquinolinesulphonamide	DMTF1HL	Discovery agent	N.A.	Investigative	[2]
2-(2-Hydroxy-phenyl)-1H-indole-5-carboxamidine	DM3UMYD	Discovery agent	N.A.	Investigative	[3]
5-(DIMETHYLAMINO)-2-NAPHTHALENESULFONIC ACID	DMPFX0S	Discovery agent	N.A.	Investigative	[4]
BMS-344577	DM9WRUG	Discovery agent	N.A.	Investigative	[5]
N-(4-Chloro-7-p-tolyl-isoquinolin-1-yl)-guanidine	DMNO46U	Discovery agent	N.A.	Investigative	[6]
N-(4-Phenyl-pyridin-2-yl)-guanidine	DMYD4PC	Discovery agent	N.A.	Investigative	[7]
N-(5-Benzyloxy-isoquinolin-1-yl)-guanidine	DMGAITY	Discovery agent	N.A.	Investigative	[6]
N-(7-Benzyloxy-isoquinolin-1-yl)-guanidine	DMPMBC2	Discovery agent	N.A.	Investigative	[6]

References

• [1] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [2] Selective urokinase-type plasminogen activator inhibitors. 4. 1-(7-sulfonamidoisoquinolinyl)guanidines. J Med Chem. 2007 May 17;50(10):2341-51.
• [3] Development of serine protease inhibitors displaying a multicentered short (<2.3 A) hydrogen bond binding mode: inhibitors of urokinase-type plasmi... J Med Chem. 2001 Aug 16;44(17):2753-71.
• [4] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [5] Aroylguanidine-based factor Xa inhibitors: the discovery of BMS-344577. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6882-9.
• [6] Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-isoquinolinylguanidines. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3227-30.
• [7] Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 1: 2-Pyridinylguanidines. Bioorg Med Chem Lett. 2002 Jan 21;12(2):181-4.