General Information of Drug Combination (ID: DC0GIZ0)

Drug Combination Name
Aciclovir Tetracycline
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Aciclovir   DMYLOVR Tetracycline   DMZA017
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: 31.17
Bliss Independence Score: 31.17
Loewe Additivity Score: 40.9
LHighest Single Agent (HSA) Score: 40.92

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]
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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 [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]
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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 [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]
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⏷ Show the Full List of 12 DOT(s)
Indication(s) of Tetracycline
Disease Entry ICD 11 Status REF
Acne vulgaris ED80 Approved [9]
Actinomycosis N.A. Approved [9]
Acute gonococcal cervicitis N.A. Approved [9]
Acute gonococcal epididymo-orchitis N.A. Approved [9]
Bacterial infection 1A00-1C4Z Approved [10]
Bronchitis CA20 Approved [9]
Brucellosis N.A. Approved [9]
Lymphogranuloma venereum N.A. Approved [9]
Ornithosis N.A. Approved [9]
Pneumonia CA40 Approved [9]
Q fever N.A. Approved [9]
Relapsing fever N.A. Approved [9]
Rickettsialpox N.A. Approved [9]
Rocky mountain spotted fever N.A. Approved [9]
Syphilis N.A. Approved [9]
Trachoma N.A. Approved [9]
Typhus N.A. Approved [9]
Urinary tract infection GC08 Approved [9]
Yaws N.A. Approved [9]
Pelvic inflammatory disease GA05 Investigative [9]
Sinusitis CA0A.Z Investigative [9]
Tetracycline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Staphylococcus 30S ribosomal subunit (Stap-coc pbp2) TTQ8KVI F4NA87_STAAU Binder [26]
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Tetracycline Interacts with 5 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [27]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [28]
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [29]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [29]
Organic anion transporter 4 (SLC22A11) DT06JWZ S22AB_HUMAN Substrate [29]
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Tetracycline Interacts with 44 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Solute carrier family 22 member 7 (SLC22A7) OTKTNH1W S22A7_HUMAN Increases Transport [30]
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Increases Uptake [29]
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Decreases Activity [31]
Glutathione S-transferase Mu 3 (GSTM3) OTLA2WJT GSTM3_HUMAN Decreases Activity [31]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [25]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Expression [25]
Asparagine synthetase (ASNS) OT8R922G ASNS_HUMAN Increases Expression [25]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [25]
AP-1 complex subunit sigma-1A (AP1S1) OTQ2H8DN AP1S1_HUMAN Decreases Expression [25]
Transgelin (TAGLN) OTAEZ0KP TAGL_HUMAN Decreases Expression [25]
Fibronectin type III domain-containing protein 4 (FNDC4) OTOQK0WK FNDC4_HUMAN Increases Expression [25]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [25]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [32]
Alternative prion protein (PRNP) OTE85L1Q APRIO_HUMAN Affects Binding [33]
Claudin-11 (CLDN11) OTNN6UTL CLD11_HUMAN Decreases Expression [34]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Activity [35]
Stromelysin-1 (MMP3) OTGBI74Z MMP3_HUMAN Decreases Activity [35]
Integrin alpha-5 (ITGA5) OT3RCI67 ITA5_HUMAN Increases Expression [34]
Insulin-like growth factor-binding protein 1 (IGFBP1) OT6UQV2K IBP1_HUMAN Increases Expression [36]
Integrin alpha-M (ITGAM) OTAG6HWU ITAM_HUMAN Decreases Expression [34]
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Decreases Expression [37]
Integrin alpha-L (ITGAL) OTCUQAIS ITAL_HUMAN Decreases Expression [34]
Neutrophil collagenase (MMP8) OTZXH19L MMP8_HUMAN Decreases Activity [35]
Integrin alpha-3 (ITGA3) OTBCH21D ITA3_HUMAN Decreases Expression [34]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [38]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [38]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Increases Expression [36]
Collagenase 3 (MMP13) OTY8BZIE MMP13_HUMAN Decreases Activity [35]
Gap junction alpha-8 protein (GJA8) OTZCPRKD CXA8_HUMAN Decreases Expression [34]
Microsomal triglyceride transfer protein large subunit (MTTP) OTNUVSDT MTP_HUMAN Decreases Expression [36]
Claudin-15 (CLDN15) OT9K0KI7 CLD15_HUMAN Decreases Expression [34]
Claudin-6 (CLDN6) OTEN8ID2 CLD6_HUMAN Decreases Expression [34]
Claudin-8 (CLDN8) OT7IIWXG CLD8_HUMAN Decreases Expression [34]
Claudin-2 (CLDN2) OTRF3D6Y CLD2_HUMAN Decreases Expression [34]
Claudin-10 (CLDN10) OT2CVAKY CLD10_HUMAN Decreases Expression [34]
Peroxisomal bifunctional enzyme (EHHADH) OTBAAHL5 ECHP_HUMAN Decreases Expression [36]
Diacylglycerol O-acyltransferase 2 (DGAT2) OTE5PDD0 DGAT2_HUMAN Increases Expression [38]
Neurogenic locus notch homolog protein 4 (NOTCH4) OTBCHB61 NOTC4_HUMAN Decreases Expression [34]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Increases Expression [39]
Gap junction delta-2 protein (GJD2) OTDR288R CXD2_HUMAN Decreases Expression [34]
Neurogenic locus notch homolog protein 3 (NOTCH3) OTMVVA7F NOTC3_HUMAN Decreases Expression [34]
Solute carrier family 22 member 6 (SLC22A6) OTKRCBVM S22A6_HUMAN Increases Export [29]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Increases Transport [40]
Organic anion transporter 7 (SLC22A9) OTO4BJCC S22A9_HUMAN Increases Export [29]
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⏷ Show the Full List of 44 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 Tetracycline FDA Label
10 How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
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 Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
26 The glycylcyclines: a comparative review with the tetracyclines. Drugs. 2004;64(1):63-88.
27 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
28 Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem J. 2005 Jan 15;385(Pt 2):419-26.
29 Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76.
30 Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). J Pharm Pharmacol. 2005 May;57(5):573-8.
31 Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002 Feb 10;97(5):700-5.
32 A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine. Drug Metab Dispos. 2008 Aug;36(8):1689-97.
33 Tetracycline affects abnormal properties of synthetic PrP peptides and PrP(Sc) in vitro. J Mol Biol. 2000 Jul 28;300(5):1309-22. doi: 10.1006/jmbi.2000.3840.
34 Effects of residual levels of tetracycline on the barrier functions of human intestinal epithelial cells. Food Chem Toxicol. 2017 Nov;109(Pt 1):253-263. doi: 10.1016/j.fct.2017.09.004. Epub 2017 Sep 4.
35 Synthesis and in vitro evaluation of targeted tetracycline derivatives: effects on inhibition of matrix metalloproteinases. Bioorg Med Chem. 2007 Mar 15;15(6):2368-74. doi: 10.1016/j.bmc.2007.01.026. Epub 2007 Jan 19.
36 Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis. Toxicol Appl Pharmacol. 2016 Jul 1;302:1-9. doi: 10.1016/j.taap.2016.04.007. Epub 2016 Apr 16.
37 Old drug, new target: ellipticines selectively inhibit RNA polymerase I transcription. J Biol Chem. 2013 Feb 15;288(7):4567-82. doi: 10.1074/jbc.M112.411611. Epub 2013 Jan 4.
38 Increased hepatic Fatty Acid uptake and esterification contribute to tetracycline-induced steatosis in mice. Toxicol Sci. 2015 Jun;145(2):273-82. doi: 10.1093/toxsci/kfv049. Epub 2015 Mar 4.
39 Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
40 Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res. 2007 Dec;24(12):2281-96.