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

General Information of Drug (ID: DMTF1HL)

• Drug Name: 1-guanidino-N-phenyl-7-isoquinolinesulphonamide Drug Info
• Synonyms: SCHEMBL6435184; CHEMBL227781; BDBM16131; NNEJXIJKGKRBBF-UHFFFAOYSA-N; 1-guanidino-7-sulfonamidoisoquinoline 5; 1-guanidino-7-phenylsulphamoylisoquinoline

Indication

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

• Cross-matching ID:
  PubChem CID: 16658631
  TTD Drug ID: DMTF1HL

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 Tissue-type plasminogen activator (PLAT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminocaproic Acid	DMFGND4	Bleeding disorder	GA20-GA21	Approved	[12]
2-(2-Hydroxy-phenyl)-1H-indole-5-carboxamidine	DM3UMYD	Discovery agent	N.A.	Investigative	[13]
BMS-344577	DM9WRUG	Discovery agent	N.A.	Investigative	[14]
N-(4-Chloro-7-p-tolyl-isoquinolin-1-yl)-guanidine	DMNO46U	Discovery agent	N.A.	Investigative	[10]
5-(DIMETHYLAMINO)-2-NAPHTHALENESULFONIC ACID	DMPFX0S	Discovery agent	N.A.	Investigative	[15]
N-(4-Phenyl-pyridin-2-yl)-guanidine	DMYD4PC	Discovery agent	N.A.	Investigative	[16]
N-(7-Benzyloxy-isoquinolin-1-yl)-guanidine	DMPMBC2	Discovery agent	N.A.	Investigative	[10]
N-(5-Benzyloxy-isoquinolin-1-yl)-guanidine	DMGAITY	Discovery agent	N.A.	Investigative	[10]

Drug(s) Targeting Plasminogen (PLG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ranolazine	DM0C9IL	Acute coronary syndrome	BA41	Approved	[17]
Aminocaproic Acid	DMFGND4	Bleeding disorder	GA20-GA21	Approved	[18]
Streptokinase	DM5JQ0D	Pulmonary embolism	BB00	Approved	[19]
Tranexamic Acid	DMFI8A7	Excessive bleeding	GA30.02	Approved	[20]
Alteplase	DMRJ3YX	Acute myocardial infarction	BA41	Approved	[21]
Tenecteplase	DMJYN25	Acute myocardial infarction	BA41	Approved	[21]
Anistreplase	DM6Q4B0	Acute coronary syndrome	BA41	Approved	[22]
Reteplase	DML0D1P	Heart attack	BA41	Approved	[23]
MELAGATRAN	DM4W8RE	N. A.	N. A.	Phase 3	[24]
Desmoteplase	DMDLU4Z	Ischemic stroke	8B11.5Z	Phase 3	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Plasminogen (PLG)	TTP86E2	PLMN_HUMAN	Inhibitor	[1]
Tissue-type plasminogen activator (PLAT)	TTXAGYU	TPA_HUMAN	Inhibitor	[1]
Urokinase-type plasminogen activator (PLAU)	TTGY7WI	UROK_HUMAN	Inhibitor	[1]

References

• [1] Selective urokinase-type plasminogen activator inhibitors. 4. 1-(7-sulfonamidoisoquinolinyl)guanidines. J Med Chem. 2007 May 17;50(10):2341-51.
• [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] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [13] 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.
• [14] Aroylguanidine-based factor Xa inhibitors: the discovery of BMS-344577. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6882-9.
• [15] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [16] Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 1: 2-Pyridinylguanidines. Bioorg Med Chem Lett. 2002 Jan 21;12(2):181-4.
• [17] Tranexamic acid in trauma: how should we use it. J Trauma Acute Care Surg. 2013 Jun;74(6):1575-86.
• [18] The blockage of the high-affinity lysine binding sites of plasminogen by EACA significantly inhibits prourokinase-induced plasminogen activation. Biochim Biophys Acta. 2002 Apr 29;1596(2):182-92.
• [19] Acute anuric renal failure with streptokinase therapy in a patient with acute venous thromboembolic disease and the review of renal side effects of streptokinase. Tuberk Toraks. 2008;56(4):456-61.
• [20] Evaluation of aprotinin and tranexamic acid in different in vitro and in vivo models of fibrinolysis, coagulation and thrombus formation. J Thromb Haemost. 2007 Oct;5(10):2113-8.
• [21] Thrombolytic therapies: the current state of affairs. J Endovasc Ther. 2005 Apr;12(2):224-32.
• [22] Evaluation of thrombolytic agents. Drugs. 1997;54 Suppl 3:11-6; discussion 16-7.
• [23] Fibrin binding and the regulation of plasminogen activators during thrombolytic therapy. Cardiovasc Hematol Agents Med Chem. 2008 Jul;6(3):212-23.
• [24] Orally active thrombin inhibitors. Part 1: optimization of the P1-moiety. Bioorg Med Chem Lett. 2006 May 15;16(10):2641-7.
• [25] Vampire bat salivary plasminogen activator (desmoteplase): a unique fibrinolytic enzyme that does not promote neurodegeneration. Stroke. 2003 Feb;34(2):537-43.