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

General Information of Drug (ID: DMFULZO)

• Drug Name: Macrocyclic tripeptide motif Drug Info
• Synonyms: macrocyclic tripeptide motif; CHEMBL317974

Indication

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

• Cross-matching ID:
  PubChem CID: 44331282
  TTD Drug ID: DMFULZO

Molecule-Related Drug Atlas

Drug(s) Targeting Cationic trypsinogen (PRSS1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bortezomib	DMNO38U	Leukemia		Approved	[2]
MELAGATRAN	DM4W8RE	N. A.	N. A.	Phase 3	[3]
Ulinastatin	DMIQCFG	Premature labour	JB00	Phase 3	[4]
Alpha-1 antitrypsin	DM5EFXZ	Coagulation defect	3B10.0	Phase 2	[5]
Dermolastin	DM6WSU2	Atopic dermatitis	EA80	Discontinued in Phase 2	[6]
RWJ-56423	DM6BIHE	Asthma	CA23	Discontinued in Phase 1	[7]
Patamostat	DM6HBQJ	Hypotension	BA20-BA21	Terminated	[5]
BMY-44621	DM8R3N0	N. A.	N. A.	Terminated	[8]
Grassystatin a	DM1PWX2	Discovery agent	N.A.	Investigative	[9]
2-(2-Hydroxy-phenyl)-1H-indole-5-carboxamidine	DM3UMYD	Discovery agent	N.A.	Investigative	[10]

Drug(s) Targeting Coagulation factor IIa (F2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Argatroban	DMFI46A	Thrombosis	DB61-GB90	Approved	[11]
Pyridoxal Phosphate	DMO2K0J	Malnutrition	5B50-5B71	Approved	[12]
Bivalirudin	DMECRX1	Thrombocytopenia	3B64	Approved	[13]
Ximelegatran	DMU8ANS	Myocardial infarction	BA41-BA43	Approved	[14]
Dabigatran	DMDI6R4	Stroke	8B20	Approved	[15]
Desirudin Recombinant	DM2BTFN	Coagulation defect	3B10.0	Approved	[16]
Human prothrombin complex concentrate	DMPHVQ1	Bleeding disorder	GA20-GA21	Approved	[17]
Lepirudin	DM1I3D5	Thrombocytopenia	3B64	Approved	[18]
Anisindione	DM2C48U	Coagulation defect	3B10.0	Approved	[19]
ATryn antithrombin	DM79Y2T	Multiple sclerosis	8A40	Approved	[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	Inhibitor	[1]
Coagulation factor IIa (F2)	TT6L509	THRB_HUMAN	Inhibitor	[1]

References

• [1] Novel thrombin inhibitors that are based on a macrocyclic tripeptide motif, Bioorg. Med. Chem. Lett. 6(24):2947-2952 (1996).
• [2] 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.
• [3] Orally active thrombin inhibitors. Part 1: optimization of the P1-moiety. Bioorg Med Chem Lett. 2006 May 15;16(10):2641-7.
• [4] 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.
• [5] 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.
• [6] Arriva-ProMetic recombinant alpha 1-antitrypsin (rAAT) moves into the clinic for dermatology applications. ProMetic Life Sciences. 2009.
• [7] 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.
• [8] Design and synthesis of conformationally constrained arginal thrombin inhibitors, Bioorg. Med. Chem. Lett. 7(17):2205-2210 (1997).
• [9] Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation. J Med Chem. 2009 Sep 24;52(18):5732-47.
• [10] 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.
• [11] Studies on the different modes of action of the anticoagulant protease inhibitors DX-9065a and Argatroban. I. Effects on thrombin generation. J Biol Chem. 2002 Dec 27;277(52):50439-44.
• [12] New antithrombotic drugs (excluding plasminogen activators. Arch Mal Coeur Vaiss. 2001 Nov;94(11 Suppl):1225-32.
• [13] New anticoagulants. Am Heart J. 2001 Aug;142(2 Suppl):S3-8.
• [14] Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
• [15] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [17] 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: 2362).
• [18] Recombinant hirudin (lepirudin) as anticoagulant in intensive care patients treated with continuous hemodialysis. Kidney Int Suppl. 1999 Nov;(72):S46-50.
• [19] Anticoagulation with anisindione in a patient with a warfarin-induced skin eruption. Pharmacotherapy. 2003 Apr;23(4):533-6.
• [20] Antithrombin III Utilization in a Large Teaching Hospital. P T. 2013 December; 38(12): 764-767, 779.