Details of the Drug Combination

General Information of Drug Combination (ID: DCZRL8T)

Drug Combination Name
Mecamylamine Bepridil
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Mecamylamine   DMGQFYB Bepridil   DM0RKS4
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: 6.24
Bliss Independence Score: 6.24
Loewe Additivity Score: 20.64
LHighest Single Agent (HSA) Score: 20.64

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Mecamylamine
Disease Entry ICD 11 Status REF
Essential hypertension BA00 Approved [2]
Mecamylamine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Nicotinic acetylcholine receptor (nAChR) TTJSZTB NOUNIPROTAC Antagonist [5]
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Mecamylamine Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Dihydrofolate reductase (DHFR) OT3DVIGM DYR_HUMAN Decreases Expression [4]
Receptor-type tyrosine-protein phosphatase alpha (PTPRA) OTZA82J1 PTPRA_HUMAN Decreases Expression [4]
Contactin-1 (CNTN1) OT7RNPEY CNTN1_HUMAN Increases Expression [4]
Fasciculation and elongation protein zeta-1 (FEZ1) OTWCXPRE FEZ1_HUMAN Decreases Expression [4]
Lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF) OTT5JX1F LITAF_HUMAN Decreases Expression [4]
Echinoderm microtubule-associated protein-like 4 (EML4) OTJC45TA EMAL4_HUMAN Decreases Expression [4]
Stress-induced-phosphoprotein 1 (STIP1) OT7TXLOX STIP1_HUMAN Decreases Expression [6]
Golgin subfamily A member 4 (GOLGA4) OTCMEHNJ GOGA4_HUMAN Increases Expression [6]
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⏷ Show the Full List of 8 DOT(s)
Indication(s) of Bepridil
Disease Entry ICD 11 Status REF
Chronic/stable angina BA40.1 Approved [3]
Bepridil Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Calcium channel unspecific (CaC) TT5HONZ NOUNIPROTAC Modulator [7]
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Bepridil Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
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Bepridil Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [10]
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Bepridil Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [11]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [11]
Potassium voltage-gated channel subfamily A member 5 (KCNA5) OTHI2N71 KCNA5_HUMAN Decreases Activity [12]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [11]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10) OT4PXBTA TNF10_HUMAN Increases Response To Substance [11]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [13]
Eukaryotic translation initiation factor 2A (EIF2A) OTWXELQP EIF2A_HUMAN Increases Phosphorylation [11]
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⏷ Show the Full List of 7 DOT(s)

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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 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: 2337).
4 Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line. J Biol Chem. 2003 May 2;278(18):15633-40.
5 Mecamylamine (Inversine): an old antihypertensive with new research directions. J Hum Hypertens. 2002 Jul;16(7):453-7.
6 Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
8 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
9 Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17.
10 Serum flecainide S/R ratio reflects the CYP2D6 genotype and changes in CYP2D6 activity. Drug Metab Pharmacokinet. 2015 Aug;30(4):257-62.
11 Amiodarone sensitizes human glioma cells but not astrocytes to TRAIL-induced apoptosis via CHOP-mediated DR5 upregulation. Neuro Oncol. 2011 Mar;13(3):267-79. doi: 10.1093/neuonc/noq195. Epub 2011 Feb 3.
12 Inhibitory effect of bepridil on hKv1.5 channel current: comparison with amiodarone and E-4031. Eur J Pharmacol. 2001 Nov 2;430(2-3):149-57. doi: 10.1016/s0014-2999(01)01381-4.
13 Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds. Assay Drug Dev Technol. 2004 Oct;2(5):497-506. doi: 10.1089/adt.2004.2.497.