Details of the Drug Combination

General Information of Drug Combination (ID: DCSWTV2)

Drug Combination Name
Sivelestat Maprotiline
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Sivelestat   DM6BZCV Maprotiline   DMPWB7T
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 6.75
Bliss Independence Score: 6.75
Loewe Additivity Score: 7.78
LHighest Single Agent (HSA) Score: 7.78

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Sivelestat
Disease Entry ICD 11 Status REF
Crohn disease DD70 Phase 3 [2]
Multiple sclerosis 8A40 Phase 3 [2]
Psoriatic arthritis FA21 Phase 3 [2]
Pyoderma gangrenosum EB21 Phase 3 [3]
Rheumatoid arthritis FA20 Phase 3 [2]
Ulcerative colitis DD71 Phase 3 [2]
Anterior uveitis 9A96 Application submitted [4]
Axial spondyloarthritis FA92.0 Application submitted [2]
Sivelestat Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Pancreatic elastase 1 (CELA1) TT3NKIB CELA1_HUMAN Inhibitor [7]
Neutrophil elastase (NE) TTPLTSQ ELNE_HUMAN Inhibitor [8]
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Indication(s) of Maprotiline
Disease Entry ICD 11 Status REF
Depression 6A70-6A7Z Approved [5]
Major depressive disorder 6A70.3 Approved [6]
Mixed anxiety and depressive disorder N.A. Investigative [5]
Maprotiline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Norepinephrine transporter (NET) TTAWNKZ SC6A2_HUMAN Inhibitor [9]
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Maprotiline Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [10]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [10]
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Maprotiline Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases ADR [11]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Increases Expression [12]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Maprotiline FDA Label
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
7 Sivelestat (selective neutrophil elastase inhibitor) improves the mortality rate of sepsis associated with both acute respiratory distress syndrome... Shock. 2010 Jan;33(1):14-8.
8 Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB. Inflamm Res. 2009 Apr;58(4):198-203.
9 Effect of pharmacologically selective antidepressants on serotonin uptake in rat platelets. Gen Physiol Biophys. 2005 Mar;24(1):113-28.
10 Cytochrome P450 enzymes contributing to demethylation of maprotiline in man. Pharmacol Toxicol. 2002 Mar;90(3):144-9.
11 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
12 The antidepressants maprotiline and fluoxetine induce Type II autophagic cell death in drug-resistant Burkitt's lymphoma. Int J Cancer. 2011 Apr 1;128(7):1712-23. doi: 10.1002/ijc.25477. Epub 2010 May 25.