General Information of Drug Combination (ID: DC0HA8Q)

Drug Combination Name
Epirubicin Isoniazid
Indication
Disease Entry Status REF
Adult T acute lymphoblastic leukemia Investigative [1]
Component Drugs Epirubicin   DMPDW6T Isoniazid   DM5JVS3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: MOLT-4
Zero Interaction Potency (ZIP) Score: 2.63
Bliss Independence Score: 7.58
Loewe Additivity Score: 5.1
LHighest Single Agent (HSA) Score: 5.76

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Epirubicin
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Approved [2]
Epirubicin 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 [5]
------------------------------------------------------------------------------------
Epirubicin Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [6]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [7]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [7]
------------------------------------------------------------------------------------
Epirubicin Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [8]
------------------------------------------------------------------------------------
Epirubicin Interacts with 19 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [9]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Response To Substance [10]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Increases Expression [11]
Interleukin-6 receptor subunit alpha (IL6R) OTCQL07Z IL6RA_HUMAN Increases Expression [12]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [13]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [13]
Protein PML (PML) OT6SM2GD PML_HUMAN Affects Mutagenesis [14]
FK506-binding protein-like (FKBPL) OTR9ND6K FKBPL_HUMAN Increases Expression [15]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Increases ADR [16]
MARVEL domain-containing protein 1 (MARVELD1) OT5CPOJE MALD1_HUMAN Increases Response To Substance [17]
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) OT9AGAIJ LHPP_HUMAN Increases ADR [16]
Alpha-protein kinase 1 (ALPK1) OTBW6SGD ALPK1_HUMAN Increases ADR [18]
Baculoviral IAP repeat-containing protein 6 (BIRC6) OTCQJAB0 BIRC6_HUMAN Decreases Response To Substance [19]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Response To Substance [20]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Affects Response To Substance [21]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Response To Substance [22]
Pleckstrin homology-like domain family A member 2 (PHLDA2) OTMV9DPP PHLA2_HUMAN Increases Response To Substance [23]
Little elongation complex subunit 1 (ICE1) OTOXTBUH ICE1_HUMAN Increases ADR [16]
Microcephalin (MCPH1) OTYT3TT5 MCPH1_HUMAN Increases ADR [18]
------------------------------------------------------------------------------------
⏷ Show the Full List of 19 DOT(s)
Indication(s) of Isoniazid
Disease Entry ICD 11 Status REF
Latent tuberculosis infection N.A. Approved [3]
Pulmonary tuberculosis 1B10.Z Approved [3]
Tuberculosis 1B10-1B1Z Approved [4]
Isoniazid Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial Fatty acid synthetase I (Bact inhA) TTVTX4N INHA_MYCTU Inhibitor [25]
------------------------------------------------------------------------------------
Isoniazid Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [26]
Catalase-peroxidase (katG) DEAGY5M KATG_SYNE7 Metabolism [27]
Arylamine N-acetyltransferase (NAT) DEXCQTM A0A3P8LE58_TSUPA Metabolism [28]
------------------------------------------------------------------------------------
Isoniazid Interacts with 28 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
N-alpha-acetyltransferase 20 (NAA20) OTJB0VA6 NAA20_HUMAN Increases ADR [29]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [30]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [30]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [30]
Aldo-keto reductase family 1 member B10 (AKR1B10) OTOA4HTH AK1BA_HUMAN Increases Expression [24]
Interleukin-12 subunit alpha (IL12A) OTDQT8GI IL12A_HUMAN Increases Secretion [24]
Interleukin-12 subunit beta (IL12B) OT0JF8A3 IL12B_HUMAN Increases Secretion [24]
Sulfiredoxin-1 (SRXN1) OTYDBO4L SRXN1_HUMAN Increases Expression [24]
Gamma-butyrobetaine dioxygenase (BBOX1) OTKEX4RK BODG_HUMAN Increases Expression [31]
Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1) OTTO6ZP4 AT1B1_HUMAN Increases Expression [31]
Amyloid-beta precursor protein (APP) OTKFD7R4 A4_HUMAN Increases Expression [31]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Decreases Expression [31]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Decreases Expression [31]
Claudin-2 (CLDN2) OTRF3D6Y CLD2_HUMAN Increases Expression [31]
Large neutral amino acids transporter small subunit 1 (SLC7A5) OT2WPVXD LAT1_HUMAN Decreases Expression [31]
Tribbles homolog 3 (TRIB3) OTG5OS7X TRIB3_HUMAN Increases Expression [31]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) OTKOZRZP PLOD2_HUMAN Increases Expression [32]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [33]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [34]
5-aminolevulinate synthase, non-specific, mitochondrial (ALAS1) OTQY6ZSF HEM1_HUMAN Increases Expression [35]
Ferrochelatase, mitochondrial (FECH) OTDWEI6C HEMH_HUMAN Decreases Expression [35]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [36]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [36]
Nuclear respiratory factor 1 (NRF1) OTOXWNV8 NRF1_HUMAN Decreases Expression [37]
Natural cytotoxicity triggering receptor 3 ligand 1 (NCR3LG1) OT15YWU7 NR3L1_HUMAN Increases Expression [38]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [34]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) OTHCDQ22 PRGC1_HUMAN Decreases Expression [37]
Arylamine N-acetyltransferase 2 (NAT2) OTBPDQOY ARY2_HUMAN Decreases Acetylation [39]
------------------------------------------------------------------------------------
⏷ Show the Full List of 28 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Clear cell renal cell carcinoma DCR3RWS 786-0 Investigative [1]
Clear cell renal cell carcinoma DCJVUR0 A498 Investigative [1]
Glioma DCMHZKG SF-268 Investigative [1]
Carcinoma DC1R0YC RXF 393 Investigative [40]
Carcinoma DCBPK86 MCF7 Investigative [40]
Adenocarcinoma DCOV6KY DU-145 Investigative [41]
Adenocarcinoma DC90KMW NCIH23 Investigative [41]
Adenocarcinoma DC6QYWN HCT116 Investigative [41]
High grade ovarian serous adenocarcinoma DCLLB4H NCI\\/ADR-RES Investigative [41]
Lung adenocarcinoma DCY519Z EKVX Investigative [41]
Malignant melanoma DCO0N59 UACC62 Investigative [41]
Melanoma DC39CLU UACC-257 Investigative [41]
Ovarian serous cystadenocarcinoma DCT6ZO4 SK-OV-3 Investigative [41]
------------------------------------------------------------------------------------
⏷ Show the Full List of 13 DrugCom(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 New drugs for the treatment of cancer, 1990-2001. Isr Med Assoc J. 2002 Dec;4(12):1124-31.
3 Isoniazid FDA Label
4 Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
6 Sulindac sulfide selectively increases sensitivity of ABCC1 expressing tumor cells to doxorubicin and glutathione depletion. J Biomed Res. 2016 Mar;30(2):120-133.
7 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.
8 Epirubicin glucuronidation and UGT2B7 developmental expression. Drug Metab Dispos. 2006 Dec;34(12):2097-101.
9 Co-encapsulation of chrysophsin-1 and epirubicin in PEGylated liposomes circumvents multidrug resistance in HeLa cells. Chem Biol Interact. 2015 Dec 5;242:13-23. doi: 10.1016/j.cbi.2015.08.023. Epub 2015 Sep 1.
10 Camptothecin resistance: role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells. Cancer Res. 1999 Dec 1;59(23):5938-46.
11 Preliminary study on behaviour of atrial natriuretic factor in anthracycline-related cardiac toxicity. Int J Clin Pharmacol Res. 1991;11(2):75-81.
12 Persistence, up to 18 months of follow-up, of epirubicin-induced myocardial dysfunction detected early by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers. Oncologist. 2008 Dec;13(12):1296-305. doi: 10.1634/theoncologist.2008-0151. Epub 2008 Dec 5.
13 (-)-Gossypol enhances the anticancer activity of epirubicin via downregulating survivin in hepatocellular carcinoma. Chem Biol Interact. 2022 Sep 1;364:110060. doi: 10.1016/j.cbi.2022.110060. Epub 2022 Jul 22.
14 Evidence for direct involvement of epirubicin in the formation of chromosomal translocations in t(15;17) therapy-related acute promyelocytic leukemia. Blood. 2010 Jan 14;115(2):326-30. doi: 10.1182/blood-2009-07-235051. Epub 2009 Nov 2.
15 The differential effects of cyclophosphamide, epirubicin and 5-fluorouracil on apoptotic marker (CPP-32), pro-apoptotic protein (p21(WAF-1)) and anti-apoptotic protein (bcl-2) in breast cancer cells. Breast Cancer Res Treat. 2003 Aug;80(3):239-44. doi: 10.1023/A:1024995202135.
16 Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. Cancer Sci. 2013 Aug;104(8):1074-82. doi: 10.1111/cas.12186. Epub 2013 Jun 10.
17 MARVELD1 attenuates arsenic trioxide-induced apoptosis in liver cancer cells by inhibiting reactive oxygen species production. Ann Transl Med. 2019 May;7(9):200. doi: 10.21037/atm.2019.04.38.
18 Genome-wide association study of epirubicin-induced leukopenia in Japanese patients. Pharmacogenet Genomics. 2011 Sep;21(9):552-8. doi: 10.1097/FPC.0b013e328348e48f.
19 [Knock-down of apollon gene by antisense oligodeoxynucleotide inhibits the proliferation of Lovo cells and enhances chemo-sensitivity]. Yao Xue Xue Bao. 2011 Feb;46(2):138-45.
20 [Antisense oligonucleotide targeting survivin induces apoptosis of renal clear-cell carcinoma cells and enhances their sensitivity to epirubicin in vitro]. Zhonghua Zhong Liu Za Zhi. 2005 Aug;27(8):468-70.
21 Endogenous antioxidant enzymes and glutathione S-transferase in protection of mesothelioma cells against hydrogen peroxide and epirubicin toxicity. Br J Cancer. 1998 Apr;77(7):1097-102. doi: 10.1038/bjc.1998.182.
22 S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3. Oncol Rep. 2008 Aug;20(2):325-32.
23 TSSC3 overexpression associates with growth inhibition, apoptosis induction and enhances chemotherapeutic effects in human osteosarcoma. Carcinogenesis. 2012 Jan;33(1):30-40. doi: 10.1093/carcin/bgr232. Epub 2011 Oct 21.
24 Characterization of drug-specific signaling between primary human hepatocytes and immune cells. Toxicol Sci. 2017 Jul 1;158(1):76-89.
25 Diversity in enoyl-acyl carrier protein reductases. Cell Mol Life Sci. 2009 May;66(9):1507-17.
26 Inhibition of CYP2E1 catalytic activity in vitro by S-adenosyl-L-methionine. Biochem Pharmacol. 2005 Apr 1;69(7):1081-93.
27 Crystal structure of the catalase-peroxidase KatG W78F mutant from Synechococcus elongatus PCC7942 in complex with the antitubercular pro-drug isoniazid. FEBS Lett. 2015 Jan 2;589(1):131-7.
28 The actinobacterium Tsukamurella paurometabola has a functionally divergent arylamine N-acetyltransferase (NAT) homolog. World J Microbiol Biotechnol. 2019 Oct 31;35(11):174.
29 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.
30 Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
31 Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq. Arch Toxicol. 2018 Aug;92(8):2517-2531.
32 Identification of differentially expressed genes in hepatic HepG2 cells treated with acetaminophen using suppression subtractive hybridization. Biol Pharm Bull. 2005 Jul;28(7):1148-53. doi: 10.1248/bpb.28.1148.
33 Auto-oxidation of Isoniazid Leads to Isonicotinic-Lysine Adducts on Human Serum Albumin. Chem Res Toxicol. 2015 Jan 20;28(1):51-8. doi: 10.1021/tx500285k. Epub 2014 Dec 9.
34 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.
35 The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis. Toxicol Sci. 2019 Mar 1;168(1):209-224. doi: 10.1093/toxsci/kfy294.
36 Quercetin protected against isoniazide-induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway. J Biochem Mol Toxicol. 2019 Sep;33(9):e22369. doi: 10.1002/jbt.22369. Epub 2019 Jul 23.
37 AMPK activator acadesine fails to alleviate isoniazid-caused mitochondrial instability in HepG2 cells. J Appl Toxicol. 2017 Oct;37(10):1219-1224. doi: 10.1002/jat.3483. Epub 2017 May 29.
38 Enhanced activation of human NK cells by drug-exposed hepatocytes. Arch Toxicol. 2020 Feb;94(2):439-448. doi: 10.1007/s00204-020-02668-8. Epub 2020 Feb 14.
39 Effects of N-acetyltransferase 2 (NAT2), CYP2E1 and Glutathione-S-transferase (GST) genotypes on the serum concentrations of isoniazid and metabolites in tuberculosis patients. J Toxicol Sci. 2008 May;33(2):187-95. doi: 10.2131/jts.33.187.
40 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
41 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976