General Information of Drug Combination (ID: DCVO7UU)

Drug Combination Name
Oseltamivir Moricizine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Oseltamivir   DMGO72P Moricizine   DMOMBJW
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: 0.41
Bliss Independence Score: 0.41
Loewe Additivity Score: 14
LHighest Single Agent (HSA) Score: 14

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Oseltamivir
Disease Entry ICD 11 Status REF
Influenza 1E30-1E32 Approved [2]
Influenza virus infection 1E30-1E32 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [4]
Oseltamivir Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Influenza Neuraminidase (Influ NA) TT50QJ3 NRAM_I33A0 Inhibitor [8]
------------------------------------------------------------------------------------
Oseltamivir Interacts with 5 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [10]
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [11]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [12]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [12]
------------------------------------------------------------------------------------
Oseltamivir Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Decreases Expression [13]
Liver carboxylesterase 1 (CES1) OT9L0LR8 EST1_HUMAN Increases Metabolism [14]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Response To Substance [15]
------------------------------------------------------------------------------------
Indication(s) of Moricizine
Disease Entry ICD 11 Status REF
Arrhythmia BC9Z Approved [5]
Long QT syndrome BC65.0 Approved [6]
Heart arrhythmia BC65 Withdrawn from market [7]
Moricizine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Voltage-gated sodium channel alpha Nav1.5 (SCN5A) TTZOVE0 SCN5A_HUMAN Blocker [16]
------------------------------------------------------------------------------------
Moricizine Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [17]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Expression [17]
------------------------------------------------------------------------------------

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 Oseltamivir FDA Label
3 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
4 ClinicalTrials.gov (NCT04261270) A Randomized,Open,Controlled Clinical Study to Evaluate the Efficacy of ASC09F and Ritonavir for 2019-nCoV Pneumonia
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6 Moricizine FDA Label
7 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: 7244).
8 Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102.
9 Nonclinical pharmacokinetics of oseltamivir and oseltamivir carboxylate in the central nervous system. Antimicrob Agents Chemother. 2009 Nov;53(11):4753-61.
10 Limited brain distribution of [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), a pharmacologically active form of oseltamivir, by active efflux across the blood-brain barrier mediated by organic anion transporter 3 (Oat3/Slc22a8) and multidrug resistance-associated protein 4 (Mrp4/Abcc4). Drug Metab Dispos. 2009 Feb;37(2):315-21.
11 Oseltamivir (tamiflu) is a substrate of peptide transporter 1. Drug Metab Dispos. 2009 Aug;37(8):1676-81.
12 FDA Drug Development and Drug Interactions
13 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
14 In vitro inhibition of carboxylesterase 1 by Kava (Piper methysticum) Kavalactones. Chem Biol Interact. 2022 Apr 25;357:109883. doi: 10.1016/j.cbi.2022.109883. Epub 2022 Mar 9.
15 Interleukin-6 alters the cellular responsiveness to clopidogrel, irinotecan, and oseltamivir by suppressing the expression of carboxylesterases HCE1 and HCE2. Mol Pharmacol. 2007 Sep;72(3):686-94. doi: 10.1124/mol.107.036889. Epub 2007 May 30.
16 From first class to third class: recent upheaval in antiarrhythmic therapy--lessons from clinical trials. Am J Cardiol. 1996 Aug 29;78(4A):28-33.
17 Comparison of immortalized Fa2N-4 cells and human hepatocytes as in vitro models for cytochrome P450 induction. Drug Metab Dispos. 2008 Jun;36(6):1046-55.