General Information of Drug Combination (ID: DC8I14E)

Drug Combination Name
Oseltamivir Aciclovir
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Oseltamivir   DMGO72P Aciclovir   DMYLOVR
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: 9.65
Bliss Independence Score: 9.65
Loewe Additivity Score: 26.79
LHighest Single Agent (HSA) Score: 26.8

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 [12]
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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 [13]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [14]
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [15]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [16]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [16]
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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 [17]
Liver carboxylesterase 1 (CES1) OT9L0LR8 EST1_HUMAN Increases Metabolism [18]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Response To Substance [19]
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Indication(s) of Aciclovir
Disease Entry ICD 11 Status REF
Genital herpes 1A94 Approved [5]
Herpes simplex encephalitis N.A. Approved [6]
Herpes simplex infection 1F00 Approved [7]
Herpes simplex labialis 1F00.01 Approved [8]
Varicella 1E90 Approved [9]
Virus infection 1A24-1D9Z Approved [10]
Herpes simplex virus infection 1F00 Phase 3 [11]
Aciclovir Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Herpes simplex virus DNA polymerase UL30 (HSV UL30) TTIU7X1 DPOL_HHV11 Modulator [20]
Varicella-zoster virus DNA polymerase (VZV ORF28) TTHPJTK DPOL_VZVD Modulator [21]
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Aciclovir Interacts with 9 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [22]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [23]
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [24]
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [25]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [26]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [26]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [27]
Multidrug and toxin extrusion protein 2 (SLC47A2) DT3TX4H S47A2_HUMAN Substrate [25]
Alanine/serine/cysteine/threonine transporter 2 (SLC1A5) DTW7AE3 AAAT_HUMAN Substrate [28]
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⏷ Show the Full List of 9 DTP(s)
Aciclovir Interacts with 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Transport [29]
Indoleamine 2,3-dioxygenase 1 (IDO1) OT91DBN7 I23O1_HUMAN Decreases Activity [30]
3-hydroxyanthranilate 3,4-dioxygenase (HAAO) OTK9Y6SG 3HAO_HUMAN Decreases Activity [30]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [17]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [17]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [17]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [17]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [17]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [17]
Major histocompatibility complex class I-related gene protein (MR1) OTZU3XX7 HMR1_HUMAN Affects Expression [31]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [17]
Myelin basic protein (MBP) OTFZCEDB MBP_HUMAN Increases ADR [32]
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⏷ Show the Full List of 12 DOT(s)

References

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2 Oseltamivir FDA Label
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4 ClinicalTrials.gov (NCT04261270) A Randomized,Open,Controlled Clinical Study to Evaluate the Efficacy of ASC09F and Ritonavir for 2019-nCoV Pneumonia
5 Genital herpes. BMJ Clin Evid. 2011 Apr 15;2011:1603.
6 Management of suspected viral encephalitis in adults--Association of British Neurologists and British Infection Association National Guidelines. J Infect. 2012 Apr;64(4):347-73.
7 Prevention and management of genital herpes simplex infection during pregnancy and delivery: Guidelines from the French College of Gynaecologists and Obstetricians (CNGOF). Eur J Obstet Gynecol Reprod Biol. 2018 May;224:93-101.
8 Interventions for prevention of herpes simplex labialis (cold sores on the lips). Cochrane Database Syst Rev. 2015 Aug 7;2015(8):CD010095.
9 Neonatal varicella. Arch Dis Child. 2023 Oct 31:archdischild-2022-324820.
10 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: 4829).
11 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
12 Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102.
13 Nonclinical pharmacokinetics of oseltamivir and oseltamivir carboxylate in the central nervous system. Antimicrob Agents Chemother. 2009 Nov;53(11):4753-61.
14 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.
15 Oseltamivir (tamiflu) is a substrate of peptide transporter 1. Drug Metab Dispos. 2009 Aug;37(8):1676-81.
16 FDA Drug Development and Drug Interactions
17 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.
18 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.
19 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.
20 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
21 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
22 Gene expression in the human intestine and correlation with oral valacyclovir pharmacokinetic parameters. J Pharmacol Exp Ther. 2003 Aug;306(2):778-86.
23 Acyclovir is a substrate for the human breast cancer resistance protein (BCRP/ABCG2): implications for renal tubular transport and acyclovir-induced nephrotoxicity. Can J Physiol Pharmacol. 2011 Sep;89(9):675-80.
24 Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP. Mol Pharmacol. 2008 Apr;73(4):1151-8.
25 Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71.
26 Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
27 Expression of organic anion transporter 2 in the human kidney and its potential role in the tubular secretion of guanine-containing antiviral drugs. Drug Metab Dispos. 2012 Mar;40(3):617-24.
28 Amino Acid Transporter ATB0,+ as a delivery system for drugs and prodrugs. Curr Drug Targets Immune Endocr Metabol Disord. 2005 Dec;5(4):357-64.
29 Acyclovir is a substrate for the human breast cancer resistance protein (BCRP/ABCG2): implications for renal tubular transport and acyclovir-induced nephrotoxicity. Can J Physiol Pharmacol. 2011 Sep;89(9):675-80. doi: 10.1139/y11-045. Epub 2011 Aug 22.
30 Mechanisms by which acyclovir reduces the oxidative neurotoxicity and biosynthesis of quinolinic acid. Life Sci. 2007 Feb 13;80(10):918-25.
31 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
32 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.