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

General Information of Drug (ID: DMBPL3J)

• Drug Name: (4-nitro-1H-pyrazol-1-yl)(o-tolyl)methanone Drug Info
• Synonyms: BAS 02052986; AC1LDSC0; N-Benzoylpyrazole deriv., 20; CHEMBL244072; ZINC37170; BDBM23712; MolPort-001-971-782; AKOS000577347; 2-methylphenyl 4-nitropyrazolyl ketone; MCULE-4726161589; ST033205; (4-Nitro-pyrazol-1-yl)-o-tolyl-methanone; (2-methylphenyl)-(4-nitropyrazol-1-yl)methanone

Indication

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

• Cross-matching ID:
  PubChem CID: 674641
  TTD Drug ID: DMBPL3J

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 Neutrophil elastase (NE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sivelestat sodium hydrate	DMOSJD0	Acute lung injury	NB32.3	Phase 4	[12]
Epigallocatechin gallate	DMCGWBJ	Hepatic fibrosis	DB93.0	Phase 3	[13]
Sivelestat	DM6BZCV	Crohn disease	DD70	Phase 3	[14]
Tiprelestat	DM1SB94	Myocardial infarction	BA41-BA43	Phase 2	[15]
AZD9668	DMB87M3	Bronchiectasis	CA24	Phase 2	[16]
L-694,458	DMA0DSJ	Cystic fibrosis	CA25	Phase 2	[17]
BAY 85-8501	DMCPUKG	Bronchiectasis	CA24	Phase 2	[18]
DX-890	DMBFZET	Acute lung injury	NB32.3	Phase 2	[12]
POL-6014	DM9B68S	Cystic fibrosis	CA25	Phase 1	[19]
AZD-9819	DMWYHXG	Chronic obstructive pulmonary disease	CA22	Phase 1	[20]

Drug(s) Targeting Coagulation factor IIa (F2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Argatroban	DMFI46A	Thrombosis	DB61-GB90	Approved	[21]
Pyridoxal Phosphate	DMO2K0J	Malnutrition	5B50-5B71	Approved	[22]
Bivalirudin	DMECRX1	Thrombocytopenia	3B64	Approved	[23]
Ximelegatran	DMU8ANS	Myocardial infarction	BA41-BA43	Approved	[5]
Dabigatran	DMDI6R4	Stroke	8B20	Approved	[24]
Desirudin Recombinant	DM2BTFN	Coagulation defect	3B10.0	Approved	[3]
Human prothrombin complex concentrate	DMPHVQ1	Bleeding disorder	GA20-GA21	Approved	[25]
Lepirudin	DM1I3D5	Thrombocytopenia	3B64	Approved	[26]
Anisindione	DM2C48U	Coagulation defect	3B10.0	Approved	[27]
ATryn antithrombin	DM79Y2T	Multiple sclerosis	8A40	Approved	[28]

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]
Neutrophil elastase (NE)	TTPLTSQ	ELNE_HUMAN	Inhibitor	[1]
Urokinase-type plasminogen activator (PLAU)	TTGY7WI	UROK_HUMAN	Inhibitor	[1]

References

• [1] N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase. J Med Chem. 2007 Oct 4;50(20):4928-38.
• [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] Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome. Expert Opin Emerg Drugs. 2007 Sep;12(3):461-77.
• [13] Evaluation of human neutrophil elastase inhibitory effect of iridoid glycosides from Hedyotis diffusa. Bioorg Med Chem Lett. 2010 Jan 15;20(2):513-5.
• [14] Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB. Inflamm Res. 2009 Apr;58(4):198-203.
• [15] Company report (Proteo Biotech AG)
• [16] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [17] Neutrophil elastase inhibitors as treatment for COPD. Expert Opin Investig Drugs. 2002 Jul;11(7):965-80.
• [18] Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 5-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases. ChemMedChem. 2015 Jul;10(7):1163-73.
• [19] 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: 2358).
• [20] Lipid Peroxide-Mediated Oxidative Rearrangement of the Pyrazinone Carboxamide Core of Neutrophil Elastase Inhibitor AZD9819 in Blood Plasma Samples. Drug Metab Dispos. 2015 Oct;43(10):1441-9.
• [21] 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.
• [22] New antithrombotic drugs (excluding plasminogen activators. Arch Mal Coeur Vaiss. 2001 Nov;94(11 Suppl):1225-32.
• [23] New anticoagulants. Am Heart J. 2001 Aug;142(2 Suppl):S3-8.
• [24] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [25] 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).
• [26] Recombinant hirudin (lepirudin) as anticoagulant in intensive care patients treated with continuous hemodialysis. Kidney Int Suppl. 1999 Nov;(72):S46-50.
• [27] Anticoagulation with anisindione in a patient with a warfarin-induced skin eruption. Pharmacotherapy. 2003 Apr;23(4):533-6.
• [28] Antithrombin III Utilization in a Large Teaching Hospital. P T. 2013 December; 38(12): 764-767, 779.