General Information of Drug Combination (ID: DC6641V)

Drug Combination Name
Aciclovir Idarubicin
Indication
Disease Entry Status REF
Glioblastoma? Investigative [1]
Component Drugs Aciclovir   DMYLOVR Idarubicin   DMM0XGL
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: T98G
Zero Interaction Potency (ZIP) Score: 20.45
Bliss Independence Score: 20.45
Loewe Additivity Score: 8
LHighest Single Agent (HSA) Score: 8

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Aciclovir
Disease Entry ICD 11 Status REF
Genital herpes 1A94 Approved [2]
Herpes simplex encephalitis N.A. Approved [3]
Herpes simplex infection 1F00 Approved [4]
Herpes simplex labialis 1F00.01 Approved [5]
Varicella 1E90 Approved [6]
Virus infection 1A24-1D9Z Approved [7]
Herpes simplex virus infection 1F00 Phase 3 [8]
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 [11]
Varicella-zoster virus DNA polymerase (VZV ORF28) TTHPJTK DPOL_VZVD Modulator [12]
------------------------------------------------------------------------------------
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 [13]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [14]
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [15]
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [16]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [17]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [17]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [18]
Multidrug and toxin extrusion protein 2 (SLC47A2) DT3TX4H S47A2_HUMAN Substrate [16]
Alanine/serine/cysteine/threonine transporter 2 (SLC1A5) DTW7AE3 AAAT_HUMAN Substrate [19]
------------------------------------------------------------------------------------
⏷ 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 [20]
Indoleamine 2,3-dioxygenase 1 (IDO1) OT91DBN7 I23O1_HUMAN Decreases Activity [21]
3-hydroxyanthranilate 3,4-dioxygenase (HAAO) OTK9Y6SG 3HAO_HUMAN Decreases Activity [21]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [22]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [22]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [22]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [22]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [22]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [22]
Major histocompatibility complex class I-related gene protein (MR1) OTZU3XX7 HMR1_HUMAN Affects Expression [23]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [22]
Myelin basic protein (MBP) OTFZCEDB MBP_HUMAN Increases ADR [24]
------------------------------------------------------------------------------------
⏷ Show the Full List of 12 DOT(s)
Indication(s) of Idarubicin
Disease Entry ICD 11 Status REF
Acute myelogenous leukaemia 2A41 Approved [9]
Acute myeloid leukaemia 2A60 Approved [10]
Adult acute monocytic leukemia N.A. Approved [9]
Childhood acute megakaryoblastic leukemia N.A. Approved [9]
Leukemia N.A. Approved [9]
Idarubicin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Modulator [11]
------------------------------------------------------------------------------------
Idarubicin Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [26]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [27]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [27]
------------------------------------------------------------------------------------
Idarubicin Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [28]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [28]
------------------------------------------------------------------------------------
Idarubicin Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Activity [25]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [29]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Increases Activity [25]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [30]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Activity [25]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [31]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Decreases Activity [25]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [32]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Decreases Activity [25]
------------------------------------------------------------------------------------
⏷ Show the Full List of 9 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 Genital herpes. BMJ Clin Evid. 2011 Apr 15;2011:1603.
3 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.
4 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.
5 Interventions for prevention of herpes simplex labialis (cold sores on the lips). Cochrane Database Syst Rev. 2015 Aug 7;2015(8):CD010095.
6 Neonatal varicella. Arch Dis Child. 2023 Oct 31:archdischild-2022-324820.
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: 4829).
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
9 Idarubicin FDA Label
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: 7083).
11 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
12 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
13 Gene expression in the human intestine and correlation with oral valacyclovir pharmacokinetic parameters. J Pharmacol Exp Ther. 2003 Aug;306(2):778-86.
14 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.
15 Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP. Mol Pharmacol. 2008 Apr;73(4):1151-8.
16 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.
17 Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
18 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.
19 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.
20 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.
21 Mechanisms by which acyclovir reduces the oxidative neurotoxicity and biosynthesis of quinolinic acid. Life Sci. 2007 Feb 13;80(10):918-25.
22 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.
23 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.
24 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.
25 Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
26 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
27 Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
28 In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
29 A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. J Am Soc Nephrol. 2016 Apr;27(4):1015-28. doi: 10.1681/ASN.2015010060. Epub 2015 Aug 10.
30 The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.
31 The induction of apoptosis by daunorubicin and idarubicin in human trisomic and diabetic fibroblasts. Cell Mol Biol Lett. 2008;13(2):182-94. doi: 10.2478/s11658-007-0045-7. Epub 2008 Apr 10.
32 Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.