Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMPJRHX)

• Drug Name: ATF-HI-8 Drug Info
• Synonyms: urokinase/urinary trypsin inhibitor chimera, Nissin/Hamamatsu University

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID: TTD Drug ID: DMPJRHX

Molecule-Related Drug Atlas

Drug(s) Targeting Urokinase-type plasminogen activator (PLAU)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pro-urokinase	DMGKT2L	Thrombin deficiency	3B14.Z	Approved	[2]
Urokinase	DM0GOUD	Myocardial infarction	BA41-BA43	Approved	[3]
PAI-1	DMY2AEF	N. A.	N. A.	Phase 4	[4]
Amediplase	DM4FPM3	Myocardial infarction	BA41-BA43	Phase 3	[5]
Upamostat	DMFZULI	Breast cancer	2C60-2C65	Phase 2	[6]
Saruplase	DM1M0PR	Thrombosis	DB61-GB90	Phase 2	[7]
HTU-PA	DMNHE43	Cerebrovascular ischaemia	8B1Z	Phase 1/2	[8]
PMID18163548C4	DMHPME3	Myocardial ischemia	BA6Z	Clinical trial	[9]
UK-356202	DMSRK2A	Myocardial hypertrophy	BC45	Clinical trial	[10]
PAI-2	DMRSMW8	N. A.	N. A.	Discontinued in Phase 2	[11]

Drug(s) Targeting Cationic trypsinogen (PRSS1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bortezomib	DMNO38U	Leukemia		Approved	[12]
MELAGATRAN	DM4W8RE	N. A.	N. A.	Phase 3	[13]
Ulinastatin	DMIQCFG	Premature labour	JB00	Phase 3	[14]
Alpha-1 antitrypsin	DM5EFXZ	Coagulation defect	3B10.0	Phase 2	[15]
Dermolastin	DM6WSU2	Atopic dermatitis	EA80	Discontinued in Phase 2	[16]
RWJ-56423	DM6BIHE	Asthma	CA23	Discontinued in Phase 1	[17]
Patamostat	DM6HBQJ	Hypotension	BA20-BA21	Terminated	[15]
BMY-44621	DM8R3N0	N. A.	N. A.	Terminated	[18]
Grassystatin a	DM1PWX2	Discovery agent	N.A.	Investigative	[19]
2-(2-Hydroxy-phenyl)-1H-indole-5-carboxamidine	DM3UMYD	Discovery agent	N.A.	Investigative	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cationic trypsinogen (PRSS1)	TT2WR1T	TRY1_HUMAN	Modulator	[1]
Urokinase-type plasminogen activator (PLAU)	TTGY7WI	UROK_HUMAN	Modulator	[1]

References

• [1] Inhibitory effect of a conjugate between human urokinase and urinary trypsin inhibitor on tumor cell invasion in vitro. J Biol Chem. 1995 Apr 7;270(14):8361-6.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2393).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Urokinase-type plasminogen activator and its inhibitor PAI-1: predictors of poor response to tamoxifen therapy in recurrent breast cancer. J Natl Cancer Inst. 1995 May 17;87(10):751-6.
• [5] Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
• [6] Phase II randomised proof-of-concept study of the urokinase inhibitor upamostat (WX-671) in combination with gemcitabine compared with gemcitabine alone in patients with non-resectable, locally advanced pancreatic cancer. Br J Cancer. 2013 Mar 5;108(4):766-70.
• [7] Pharmacokinetics and pharmacodynamics of saruplase, an unglycosylated single-chain urokinase-type plasminogen activator, in patients with acute myocardial infarction. Thromb Haemost. 1994 Nov;72(5):740-4.
• [8] Characterization of the dexamethasone-induced inhibitor of plasminogen activator in HTC hepatoma cells. J Biol Chem. 1986 Mar 25;261(9):4352-7.
• [9] Fragment-based discovery of mexiletine derivatives as orally bioavailable inhibitors of urokinase-type plasminogen activator. J Med Chem. 2008 Jan 24;51(2):183-6.
• [10] Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-isoquinolinylguanidines. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3227-30.
• [11] Topological localization of plasminogen activator inhibitor type 2. Cytometry. 2000 May 1;40(1):32-41.
• [12] Characterization of a class of peptide boronates with neutral P1 side chains as highly selective inhibitors of thrombin. J Med Chem. 1995 Apr 28;38(9):1511-22.
• [13] Orally active thrombin inhibitors. Part 1: optimization of the P1-moiety. Bioorg Med Chem Lett. 2006 May 15;16(10):2641-7.
• [14] Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in severe sepsis: a multicenter randomized controlled study. Intensive Care Med. 2014 Jun;40(6):830-8.
• [15] US patent application no. 2012,0251,516, PHARMACEUTICAL COMPOSITION FOR TREATING CANCER COMPRISING TRYPSINOGEN AND/OR CHYMOTRYPSINOGEN AND AN ACTIVE AGENT SELECTED FROM A SELENIUM COMPOUND, A VANILLOID COMPOUND AND A CYTOPLASMIC GLYCOLYSIS REDUCTION AGENT.
• [16] Arriva-ProMetic recombinant alpha 1-antitrypsin (rAAT) moves into the clinic for dermatology applications. ProMetic Life Sciences. 2009.
• [17] Inhibitors of serine proteases as potential therapeutic agents: the road from thrombin to tryptase to cathepsin G. J Med Chem. 2004 Feb 12;47(4):769-87.
• [18] Design and synthesis of conformationally constrained arginal thrombin inhibitors, Bioorg. Med. Chem. Lett. 7(17):2205-2210 (1997).
• [19] Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation. J Med Chem. 2009 Sep 24;52(18):5732-47.
• [20] 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.