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

General Information of Drug (ID: DMXAEGF)

• Drug Name: 4-iodobenzo[b]thiophene 2-carboxamidine Drug Info
• Synonyms: amino(4-iodo-1-benzothiophen-2-yl)methaniminium; ESI; AC1L1C5C; CTK7C3490; BDBM14169; APC-6860; CRA-6860; DB03136; [amino-(4-iodo-1-benzothiophen-2-yl)methylidene]azanium
• Cross-matching ID:
  PubChem CID: 1746
  TTD Drug ID: DMXAEGF

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	[4]
Urokinase	DM0GOUD	Myocardial infarction	BA41-BA43	Approved	[5]
PAI-1	DMY2AEF	N. A.	N. A.	Phase 4	[6]
Amediplase	DM4FPM3	Myocardial infarction	BA41-BA43	Phase 3	[7]
Upamostat	DMFZULI	Breast cancer	2C60-2C65	Phase 2	[8]
Saruplase	DM1M0PR	Thrombosis	DB61-GB90	Phase 2	[9]
HTU-PA	DMNHE43	Cerebrovascular ischaemia	8B1Z	Phase 1/2	[10]
PMID18163548C4	DMHPME3	Myocardial ischemia	BA6Z	Clinical trial	[11]
UK-356202	DMSRK2A	Myocardial hypertrophy	BC45	Clinical trial	[12]
PAI-2	DMRSMW8	N. A.	N. A.	Discontinued in Phase 2	[13]

Drug(s) Targeting Coagulation factor IX (F9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Emicizumab	DM0AQ83	Factor VIII deficiency	3B10	Approved	[14]
Recombinant Factor IX	DMY7ESM	Bleeding disorder	GA20-GA21	Approved	[15]
CSL-654	DMZJGVL	Factor IX deficiency	3B11	Phase 3	[16]
RG6013	DMER75Y	Haemophilia A	3B10.0	Phase 3	[17]
AMT-061	DMSO02K	Haemophilia B	3B11.0	Phase 3	[18]
Fidanacogene elaparvovec	DMFZ81T	Haemophilia B	3B11.0	Phase 3	[19]
Mim8	DMX33ZR	Haemophilia A	3B10.0	Phase 3	[20]
TTP889	DMCQARM	Blood forming organ disorder	JB64.1	Phase 2	[21]
AMT-060	DM7RNKM	Factor IX deficiency	3B11	Phase 1/2	[22]
SB-FIX	DMUP52Y	Haemophilia B	3B11.0	Phase 1/2	[23]

Drug(s) Targeting Coagulation factor IIa (F2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Argatroban	DMFI46A	Thrombosis	DB61-GB90	Approved	[24]
Pyridoxal Phosphate	DMO2K0J	Malnutrition	5B50-5B71	Approved	[25]
Bivalirudin	DMECRX1	Thrombocytopenia	3B64	Approved	[26]
Ximelegatran	DMU8ANS	Myocardial infarction	BA41-BA43	Approved	[7]
Dabigatran	DMDI6R4	Stroke	8B20	Approved	[27]
Desirudin Recombinant	DM2BTFN	Coagulation defect	3B10.0	Approved	[5]
Human prothrombin complex concentrate	DMPHVQ1	Bleeding disorder	GA20-GA21	Approved	[28]
Lepirudin	DM1I3D5	Thrombocytopenia	3B64	Approved	[29]
Anisindione	DM2C48U	Coagulation defect	3B10.0	Approved	[30]
ATryn antithrombin	DM79Y2T	Multiple sclerosis	8A40	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Coagulation factor IIa (F2)	TT6L509	THRB_HUMAN	Inhibitor	[1]
Coagulation factor IX (F9)	TTFEZ5Q	FA9_HUMAN	Inhibitor	[2]
Urokinase-type plasminogen activator (PLAU)	TTGY7WI	UROK_HUMAN	Inhibitor	[3]

References

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• [2] Studies of benzothiophene template as potent factor IXa (FIXa) inhibitors in thrombosis. J Med Chem. 2010 Feb 25;53(4):1465-72.
• [3] Structural basis for selectivity of a small molecule, S1-binding, submicromolar inhibitor of urokinase-type plasminogen activator. Chem Biol. 2000 Apr;7(4):299-312.
• [4] 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).
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] 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.
• [7] Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
• [8] 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.
• [9] 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.
• [10] Characterization of the dexamethasone-induced inhibitor of plasminogen activator in HTC hepatoma cells. J Biol Chem. 1986 Mar 25;261(9):4352-7.
• [11] 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.
• [12] Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-isoquinolinylguanidines. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3227-30.
• [13] Topological localization of plasminogen activator inhibitor type 2. Cytometry. 2000 May 1;40(1):32-41.
• [14] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [15] BAX326 (RIXUBIS): a novel recombinant factor IX for the control and prevention of bleeding episodes in adults and children with hemophilia B. Ther Adv Hematol. 2014 Oct;5(5):168-80.
• [16] Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients. Blood. 2012 September 20; 120(12): 2405-2411.
• [17] Anti-factor IXa/X bispecific antibody (ACE910): hemostatic potency against ongoing bleeds in a hemophilia A model and the possibility of routine supplementation. J Thromb Haemost. 2014 Feb;12(2):206-13.
• [18] Clinical pipeline report, company report or official report of uniQure.
• [19] Factor IX assay discrepancies in the setting of liver gene therapy using a hyperfunctional variant factor IX-Padua. J Thromb Haemost. 2021 May;19(5):1212-1218.
• [20] ClinicalTrials.gov (NCT05878938) Open-label Safety Study in Adults and Adolescents With Haemophilia A With and Without FVIII Inhibitors Switching Directly From Emicizumab Prophylaxis to NNC0365-3769 (Mim8) Prophylaxis. U.S.National Institutes of Health.
• [21] Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: an exploratory study. J Thromb Haemost. 2008 Mar;6(3):457-63.
• [22] Phase I/II clinical trial of AMT-060 for treating hemophilia B. uniQure N.V.
• [23] ClinicalTrials.gov (NCT02695160) Ascending Dose Study of Genome Editing by Zinc Finger Nuclease Therapeutic SB-FIX in Subjects With Severe Hemophilia B. U.S. National Institutes of Health.
• [24] 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.
• [25] New antithrombotic drugs (excluding plasminogen activators. Arch Mal Coeur Vaiss. 2001 Nov;94(11 Suppl):1225-32.
• [26] New anticoagulants. Am Heart J. 2001 Aug;142(2 Suppl):S3-8.
• [27] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [28] 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).
• [29] Recombinant hirudin (lepirudin) as anticoagulant in intensive care patients treated with continuous hemodialysis. Kidney Int Suppl. 1999 Nov;(72):S46-50.
• [30] Anticoagulation with anisindione in a patient with a warfarin-induced skin eruption. Pharmacotherapy. 2003 Apr;23(4):533-6.
• [31] Antithrombin III Utilization in a Large Teaching Hospital. P T. 2013 December; 38(12): 764-767, 779.