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

General Information of Drug (ID: DMCBV5F)

• Drug Name: ZK-814048 Drug Info
• Synonyms: ZK-814048; Thiophene-Anthranilamide, 10b; SCHEMBL6589576; CHEMBL227222; BDBM17090; CYFNXPSIQONWKY-UHFFFAOYSA-N; ZK814048; ZK 814048; N-(5-chloropyridin-2-yl)-2-[((4-((methylamino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide

Indication

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

• Cross-matching ID:
  PubChem CID: 16731825
  TTD Drug ID: DMCBV5F

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	[17]
(3-nitro-1H-pyrazol-1-yl)(p-tolyl)methanone	DMT9FZD	Discovery agent	N.A.	Investigative	[17]
1-benzoyl-N-phenyl-1H-pyrazole-3-carboxamide	DMG5MNZ	Discovery agent	N.A.	Investigative	[17]
D-Pro-Phe-Arg chloromethyl ketone	DMRJQ8X	Discovery agent	N.A.	Investigative	[18]

Drug(s) Targeting Coagulation factor Xa (F10)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apixaban	DM89JLN	Thrombosis	DB61-GB90	Approved	[19]
Rivaroxaban	DMQMBZ1	Deep vein thrombosis	BD71	Approved	[20]
DU-176b	DMCIJBH	Atrial fibrillation	BC81.3	Approved	[21]
Emicizumab	DM0AQ83	Factor VIII deficiency	3B10	Approved	[22]
BETRIXABAN	DM2C4RF	Venous thromboembolism	BD72	Approved	[23]
Lmw heparin	DMJPD06	Coagulation defect	3B10.0	Approved	[24]
Nadroparin calcium	DMBNKST	Coagulation defect	3B10.0	Approved	[25]
Fondaparinux sodium	DMWS3FH	Deep vein thrombosis	BD71	Approved	[26]
Danaparoid	DM6CLBN	Deep venous clot	BD71	Approved	[27]
Coagulation Factor IX	DM8HBJI	Haemophilia B	3B11.0	Approved	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Coagulation factor Xa (F10)	TTCIHJA	FA10_HUMAN	Inhibitor	[1]
Neutrophil elastase (NE)	TTPLTSQ	ELNE_HUMAN	Inhibitor	[1]
Plasma kallikrein (KLKB1)	TTMF8H9	KLKB1_HUMAN	Inhibitor	[1]

References

• [1] Thiophene-anthranilamides as highly potent and orally available factor Xa inhibitors. J Med Chem. 2007 Jun 28;50(13):2967-80.
• [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] N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase. J Med Chem. 2007 Oct 4;50(20):4928-38.
• [18] Novel 3-carboxamide-coumarins as potent and selective FXIIa inhibitors. J Med Chem. 2008 Jun 12;51(11):3077-80.
• [19] Pfizer. Product Development Pipeline. March 31 2009.
• [20] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [21] 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: 2359).
• [22] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [23] Company report (Portola)
• [24] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [25] Serum zinc concentrations: contamination from laboratory equipment. JPEN J Parenter Enteral Nutr. 1979 May-Jun;3(3):179-81.
• [26] Biochemistry and clinical pharmacology of new anticoagulant agents. Pathophysiol Haemost Thromb. 2002 Sep-Dec;32(5-6):218-24.
• [27] Effect of factor X inhibition on coagulation activation and cytokine induction in human systemic inflammation. J Infect Dis. 2002 Nov 1;186(9):1270-6.
• [28] Haemophilia B: Christmas disease. Expert Opin Pharmacother. 2005 Aug;6(9):1517-24.