General Information of Drug Combination (ID: DCZJ3UE)

Drug Combination Name
Fomepizole Aciclovir
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Fomepizole   DM6VOWQ 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: 4.89
Bliss Independence Score: 4.89
Loewe Additivity Score: 8.74
LHighest Single Agent (HSA) Score: 8.81

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Fomepizole
Disease Entry ICD 11 Status REF
Athylene glycol or methanol poisoning NE61 Approved [2]
Fomepizole Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Alcohol dehydrogenase 1A (ADH1A) TT5AHZ0 ADH1A_HUMAN Modulator [10]
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Fomepizole Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [11]
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Fomepizole Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2E1 (CYP2E1) OTHQ17JG CP2E1_HUMAN Decreases Activity [12]
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Indication(s) of Aciclovir
Disease Entry ICD 11 Status REF
Genital herpes 1A94 Approved [3]
Herpes simplex encephalitis N.A. Approved [4]
Herpes simplex infection 1F00 Approved [5]
Herpes simplex labialis 1F00.01 Approved [6]
Varicella 1E90 Approved [7]
Virus infection 1A24-1D9Z Approved [8]
Herpes simplex virus infection 1F00 Phase 3 [9]
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 [10]
Varicella-zoster virus DNA polymerase (VZV ORF28) TTHPJTK DPOL_VZVD Modulator [13]
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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 [14]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [15]
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [16]
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [17]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [18]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [18]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [19]
Multidrug and toxin extrusion protein 2 (SLC47A2) DT3TX4H S47A2_HUMAN Substrate [17]
Alanine/serine/cysteine/threonine transporter 2 (SLC1A5) DTW7AE3 AAAT_HUMAN Substrate [20]
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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 [21]
Indoleamine 2,3-dioxygenase 1 (IDO1) OT91DBN7 I23O1_HUMAN Decreases Activity [22]
3-hydroxyanthranilate 3,4-dioxygenase (HAAO) OTK9Y6SG 3HAO_HUMAN Decreases Activity [22]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [23]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [23]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [23]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [23]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [23]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [23]
Major histocompatibility complex class I-related gene protein (MR1) OTZU3XX7 HMR1_HUMAN Affects Expression [24]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [23]
Myelin basic protein (MBP) OTFZCEDB MBP_HUMAN Increases ADR [25]
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⏷ Show the Full List of 12 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 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3 Genital herpes. BMJ Clin Evid. 2011 Apr 15;2011:1603.
4 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.
5 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.
6 Interventions for prevention of herpes simplex labialis (cold sores on the lips). Cochrane Database Syst Rev. 2015 Aug 7;2015(8):CD010095.
7 Neonatal varicella. Arch Dis Child. 2023 Oct 31:archdischild-2022-324820.
8 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).
9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
10 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
11 Treatment of patients with ethylene glycol or methanol poisoning: focus on fomepizole. Open Access Emerg Med. 2010 Aug 24;2:67-75.
12 Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity. Eur J Drug Metab Pharmacokinet. 2011 Mar;36(1):1-16.
13 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
14 Gene expression in the human intestine and correlation with oral valacyclovir pharmacokinetic parameters. J Pharmacol Exp Ther. 2003 Aug;306(2):778-86.
15 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.
16 Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP. Mol Pharmacol. 2008 Apr;73(4):1151-8.
17 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.
18 Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
19 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.
20 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.
21 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.
22 Mechanisms by which acyclovir reduces the oxidative neurotoxicity and biosynthesis of quinolinic acid. Life Sci. 2007 Feb 13;80(10):918-25.
23 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.
24 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.
25 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.