Details of the Drug Combination

General Information of Drug Combination (ID: DCU29G9)

Drug Combination Name
Amantadine Mefloquine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Amantadine   DMS3YE9 Mefloquine   DMWT905
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: 4.9
Bliss Independence Score: 4.9
Loewe Additivity Score: 5.95
LHighest Single Agent (HSA) Score: 5.97

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Amantadine
Disease Entry ICD 11 Status REF
Influenza A virus infection 1E30 Approved [2]
Parkinsonian disorder N.A. Approved [3]
Postencephalitic Parkinson disease N.A. Approved [3]
Amantadine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Influenza M2 protein (Influ M) TTXT3PU M2_I34A1 Inhibitor [8]
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Amantadine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [9]
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Amantadine Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Interferon alpha-inducible protein 6 (IFI6) OTWOOAM4 IFI6_HUMAN Increases Expression [10]
Microtubule-associated protein 2 (MAP2) OT6UYT3X MTAP2_HUMAN Decreases Expression [11]
Interferon alpha/beta receptor 1 (IFNAR1) OTD4OOFK INAR1_HUMAN Affects Expression [10]
Tyrosine-protein kinase JAK1 (JAK1) OT0X3D17 JAK1_HUMAN Increases Expression [10]
2'-5'-oligoadenylate synthase 2 (OAS2) OT64CCTM OAS2_HUMAN Increases Expression [10]
Interferon alpha-inducible protein 27, mitochondrial (IFI27) OTI2XGIT IFI27_HUMAN Increases Expression [10]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [12]
Tyrosyl-DNA phosphodiesterase 1 (TDP1) OTYINMBR TYDP1_HUMAN Decreases Activity [13]
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⏷ Show the Full List of 8 DOT(s)
Indication(s) of Mefloquine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [5]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [6]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [6]
Progressive multifocal leukoencephalopathy 8A45.02 Investigative [7]
Mefloquine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Plasmodium 80S ribosome (Malaria 80S) TTT28H3 NOUNIPROTAC Binder [14]
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Mefloquine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [15]
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Mefloquine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [16]
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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: 4128).
3 Amantadine FDA Label
4 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 019578
5 ClinicalTrials.gov (NCT04347031) An Open Randomized Study of the Effectiveness of Mefloquine for the Treatment of Patients With COVID19. U.S. National Institutes of Health.
6 Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
7 Mefloquine FDA Label
8 Discovery of spiro-piperidine inhibitors and their modulation of the dynamics of the M2 proton channel from influenza A virus. J Am Chem Soc. 2009 Jun 17;131(23):8066-76.
9 Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998 Aug;54(2):342-52.
10 Interferon signal transduction of biphenyl dimethyl dicarboxylate/amantadine and anti-HBV activity in HepG2 2.2.15. Arch Pharm Res. 2006 May;29(5):405-11. doi: 10.1007/BF02968591.
11 Establishment of a 13 genes-based molecular prediction score model to discriminate the neurotoxic potential of food relevant-chemicals. Toxicol Lett. 2022 Feb 1;355:1-18. doi: 10.1016/j.toxlet.2021.10.013. Epub 2021 Nov 5.
12 Identification of human Ether--go-go related gene modulators by three screening platforms in an academic drug-discovery setting. Assay Drug Dev Technol. 2010 Dec;8(6):727-42. doi: 10.1089/adt.2010.0331.
13 Aminoadamantanes containing monoterpene-derived fragments as potent tyrosyl-DNA phosphodiesterase 1 inhibitors. Bioorg Chem. 2018 Feb;76:392-399. doi: 10.1016/j.bioorg.2017.12.005. Epub 2017 Dec 9.
14 An ultrastructural study of the effects of mefloquine on malaria parasites. Am J Trop Med Hyg. 1987 Jan;36(1):9-14.
15 Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
16 Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers. J Pharm Pharmacol. 2000 Oct;52(10):1265-9.