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

General Information of Drug (ID: DMD4Z6H)

• Drug Name: (3-nitro-1H-pyrazol-1-yl)(phenyl)methanone Drug Info
• Synonyms: (3-nitro-1H-pyrazol-1-yl)(phenyl)methanone; AC1LDSPA; 3-nitropyrazolyl phenyl ketone; N-Benzoylpyrazole deriv., 19; CHEMBL244940; 1-benzoyl-3-nitro-1H-pyrazole; BDBM23711; ZINC79624; MolPort-002-705-611; STK760577; AKOS001756309; (3-nitropyrazol-1-yl)-phenylmethanone; MCULE-2233615430; ST073764; SR-01000524822; SR-01000524822-1

Indication

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

• Cross-matching ID:
  PubChem CID: 700133
  TTD Drug ID: DMD4Z6H

Molecule-Related Drug Atlas

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	[2]
Epigallocatechin gallate	DMCGWBJ	Hepatic fibrosis	DB93.0	Phase 3	[3]
Sivelestat	DM6BZCV	Crohn disease	DD70	Phase 3	[4]
Tiprelestat	DM1SB94	Myocardial infarction	BA41-BA43	Phase 2	[5]
AZD9668	DMB87M3	Bronchiectasis	CA24	Phase 2	[6]
L-694,458	DMA0DSJ	Cystic fibrosis	CA25	Phase 2	[7]
BAY 85-8501	DMCPUKG	Bronchiectasis	CA24	Phase 2	[8]
DX-890	DMBFZET	Acute lung injury	NB32.3	Phase 2	[2]
POL-6014	DM9B68S	Cystic fibrosis	CA25	Phase 1	[9]
AZD-9819	DMWYHXG	Chronic obstructive pulmonary disease	CA22	Phase 1	[10]

Drug(s) Targeting Plasma kallikrein (KLKB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ecallantide	DMOF2C6	Retina venous occlusion	9B74.1	Approved	[11]
Lanadelumab	DMEH7YU	Hereditary angioedema	4A00.14	Approved	[12]
Berotralstat	DMWA2DZ	Hereditary angioedema	4A00.14	Approved	[13]
KVD001	DMK4VOU	Diabetic macular edema	9B71.02	Phase 2	[14]
KVD824	DM5N4OA	Diabetic macular edema	9B71.02	Phase 2	[15]
THR-149	DMW8X05	Diabetic macular edema	9B71.02	Phase 2	[16]
(4-bromo-1H-pyrazol-1-yl)(p-tolyl)methanone	DM31OSD	Discovery agent	N.A.	Investigative	[1]
(3-nitro-1H-pyrazol-1-yl)(p-tolyl)methanone	DMT9FZD	Discovery agent	N.A.	Investigative	[1]
1-benzoyl-N-phenyl-1H-pyrazole-3-carboxamide	DMG5MNZ	Discovery agent	N.A.	Investigative	[1]
D-Pro-Phe-Arg chloromethyl ketone	DMRJQ8X	Discovery agent	N.A.	Investigative	[17]

Drug(s) Targeting Coagulation factor IIa (F2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Argatroban	DMFI46A	Thrombosis	DB61-GB90	Approved	[18]
Pyridoxal Phosphate	DMO2K0J	Malnutrition	5B50-5B71	Approved	[19]
Bivalirudin	DMECRX1	Thrombocytopenia	3B64	Approved	[20]
Ximelegatran	DMU8ANS	Myocardial infarction	BA41-BA43	Approved	[21]
Dabigatran	DMDI6R4	Stroke	8B20	Approved	[22]
Desirudin Recombinant	DM2BTFN	Coagulation defect	3B10.0	Approved	[23]
Human prothrombin complex concentrate	DMPHVQ1	Bleeding disorder	GA20-GA21	Approved	[24]
Lepirudin	DM1I3D5	Thrombocytopenia	3B64	Approved	[25]
Anisindione	DM2C48U	Coagulation defect	3B10.0	Approved	[26]
ATryn antithrombin	DM79Y2T	Multiple sclerosis	8A40	Approved	[27]

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]
Plasma kallikrein (KLKB1)	TTMF8H9	KLKB1_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] Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome. Expert Opin Emerg Drugs. 2007 Sep;12(3):461-77.
• [3] Evaluation of human neutrophil elastase inhibitory effect of iridoid glycosides from Hedyotis diffusa. Bioorg Med Chem Lett. 2010 Jan 15;20(2):513-5.
• [4] Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB. Inflamm Res. 2009 Apr;58(4):198-203.
• [5] Company report (Proteo Biotech AG)
• [6] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [7] Neutrophil elastase inhibitors as treatment for COPD. Expert Opin Investig Drugs. 2002 Jul;11(7):965-80.
• [8] 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.
• [9] 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).
• [10] 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.
• [11] Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery. Expert Opin Biol Ther. 2008 Aug;8(8):1187-99.
• [12] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [14] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [15] Clinical pipeline report, company report or official report of KalVista Pharmaceuticals.
• [16] Clinical pipeline report, company report or official report of Oxurion.
• [17] Novel 3-carboxamide-coumarins as potent and selective FXIIa inhibitors. J Med Chem. 2008 Jun 12;51(11):3077-80.
• [18] 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.
• [19] New antithrombotic drugs (excluding plasminogen activators. Arch Mal Coeur Vaiss. 2001 Nov;94(11 Suppl):1225-32.
• [20] New anticoagulants. Am Heart J. 2001 Aug;142(2 Suppl):S3-8.
• [21] Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
• [22] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [23] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [24] 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).
• [25] Recombinant hirudin (lepirudin) as anticoagulant in intensive care patients treated with continuous hemodialysis. Kidney Int Suppl. 1999 Nov;(72):S46-50.
• [26] Anticoagulation with anisindione in a patient with a warfarin-induced skin eruption. Pharmacotherapy. 2003 Apr;23(4):533-6.
• [27] Antithrombin III Utilization in a Large Teaching Hospital. P T. 2013 December; 38(12): 764-767, 779.