Details of the Drug

General Information of Drug (ID: DMCBV5F)

Drug Name
ZK-814048
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]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 499.8
Topological Polar Surface Area (xlogp) 4.6
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C20H17Cl3N4O3S
IUPAC Name
3-chloro-N-[4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl]-4-(methylaminomethyl)thiophene-2-carboxamide
Canonical SMILES
CNCC1=CSC(=C1Cl)C(=O)NC2=C(C=C(C=C2OC)Cl)C(=O)NC3=NC=C(C=C3)Cl
InChI
InChI=1S/C20H17Cl3N4O3S/c1-24-7-10-9-31-18(16(10)23)20(29)27-17-13(5-12(22)6-14(17)30-2)19(28)26-15-4-3-11(21)8-25-15/h3-6,8-9,24H,7H2,1-2H3,(H,27,29)(H,25,26,28)
InChIKey
CYFNXPSIQONWKY-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
16731825
TTD ID
D02PAU

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]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Neutrophil elastase (NE) DTT ELANE 2.35E-01 -0.55 -0.82
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

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.