Details of the Drug Combination

General Information of Drug Combination (ID: DCT5QUE)

Drug Combination Name
WAY-100635 Maprotiline
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs WAY-100635   DMG58FX 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: 6.15
Bliss Independence Score: 6.15
Loewe Additivity Score: 7.7
LHighest Single Agent (HSA) Score: 7.7

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of WAY-100635
Disease Entry ICD 11 Status REF
Eating disorder 6B82 Terminated [2]
WAY-100635 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
5-HT 1A receptor (HTR1A) TTSQIFT 5HT1A_HUMAN Antagonist [5]
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WAY-100635 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
5-hydroxytryptamine receptor 1A (HTR1A) OT38K9MK 5HT1A_HUMAN Affects Binding [6]
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Indication(s) of Maprotiline
Disease Entry ICD 11 Status REF
Depression 6A70-6A7Z Approved [3]
Major depressive disorder 6A70.3 Approved [4]
Mixed anxiety and depressive disorder N.A. Investigative [3]
Maprotiline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Norepinephrine transporter (NET) TTAWNKZ SC6A2_HUMAN Inhibitor [7]
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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 [8]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [8]
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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 [9]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Increases Expression [10]
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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 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. (Ligand id: 80).
3 Maprotiline FDA Label
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5 Pharmacological characterization of recombinant human 5-hydroxytryptamine1A receptors using a novel antagonist radioligand, [3H]WAY-100635. Life Sci. 1997;60(9):653-65.
6 Design, synthesis, radiolabeling, and in vitro and in vivo evaluation of bridgehead iodinated analogues of N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexanecarboxamide (WAY-100635) as potential SPECT ligands for the 5-HT1A receptor. J Med Chem. 2011 May 26;54(10):3480-91. doi: 10.1021/jm1009956. Epub 2011 Apr 26.
7 Effect of pharmacologically selective antidepressants on serotonin uptake in rat platelets. Gen Physiol Biophys. 2005 Mar;24(1):113-28.
8 Cytochrome P450 enzymes contributing to demethylation of maprotiline in man. Pharmacol Toxicol. 2002 Mar;90(3):144-9.
9 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.
10 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.