General Information of Drug Combination (ID: DCO8HC7)

Drug Combination Name
Mechlorethamine Isoniazid
Indication
Disease Entry Status REF
Glioblastoma Investigative [1]
Component Drugs Mechlorethamine   DM0CVXA Isoniazid   DM5JVS3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SNB-75
Zero Interaction Potency (ZIP) Score: 1.27
Bliss Independence Score: 1.92
Loewe Additivity Score: 0.54
LHighest Single Agent (HSA) Score: 0.12

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Mechlorethamine
Disease Entry ICD 11 Status REF
Chronic myelogenous leukaemia 2A20.0 Approved [2]
Lung cancer 2C25.0 Approved [2]
Mycosis fungoides 2B01 Approved [2]
Primary cutaneous T-cell lymphoma N.A. Approved [2]
Small lymphocytic lymphoma 2A82.0 Approved [2]
T-cell lymphoma 2A90 Approved [3]
Hodgkin lymphoma 2B30 Phase 3 [4]
Classic Hodgkin lymphoma N.A. Investigative [2]
Mechlorethamine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Intercalator [9]
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Mechlorethamine Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Decreases Expression [10]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [11]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [11]
Transcription factor JunB (JUNB) OTG2JXV5 JUNB_HUMAN Increases Expression [11]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Increases Expression [11]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Expression [12]
Laminin subunit gamma-2 (LAMC2) OTJMTM72 LAMC2_HUMAN Decreases Expression [13]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Increases Expression [14]
Transient receptor potential cation channel subfamily A member 1 (TRPA1) OTRDIR5M TRPA1_HUMAN Increases Response To Substance [15]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of Isoniazid
Disease Entry ICD 11 Status REF
Latent tuberculosis infection N.A. Approved [5]
Pulmonary tuberculosis 1B10.Z Approved [5]
Tuberculosis 1B10-1B1Z Approved [6]
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 [17]
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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 [18]
Catalase-peroxidase (katG) DEAGY5M KATG_SYNE7 Metabolism [19]
Arylamine N-acetyltransferase (NAT) DEXCQTM A0A3P8LE58_TSUPA Metabolism [20]
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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 [21]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [22]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [22]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [22]
Aldo-keto reductase family 1 member B10 (AKR1B10) OTOA4HTH AK1BA_HUMAN Increases Expression [16]
Interleukin-12 subunit alpha (IL12A) OTDQT8GI IL12A_HUMAN Increases Secretion [16]
Interleukin-12 subunit beta (IL12B) OT0JF8A3 IL12B_HUMAN Increases Secretion [16]
Sulfiredoxin-1 (SRXN1) OTYDBO4L SRXN1_HUMAN Increases Expression [16]
Gamma-butyrobetaine dioxygenase (BBOX1) OTKEX4RK BODG_HUMAN Increases Expression [23]
Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1) OTTO6ZP4 AT1B1_HUMAN Increases Expression [23]
Amyloid-beta precursor protein (APP) OTKFD7R4 A4_HUMAN Increases Expression [23]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Decreases Expression [23]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Decreases Expression [23]
Claudin-2 (CLDN2) OTRF3D6Y CLD2_HUMAN Increases Expression [23]
Large neutral amino acids transporter small subunit 1 (SLC7A5) OT2WPVXD LAT1_HUMAN Decreases Expression [23]
Tribbles homolog 3 (TRIB3) OTG5OS7X TRIB3_HUMAN Increases Expression [23]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) OTKOZRZP PLOD2_HUMAN Increases Expression [24]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [25]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [26]
5-aminolevulinate synthase, non-specific, mitochondrial (ALAS1) OTQY6ZSF HEM1_HUMAN Increases Expression [27]
Ferrochelatase, mitochondrial (FECH) OTDWEI6C HEMH_HUMAN Decreases Expression [27]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [28]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [28]
Nuclear respiratory factor 1 (NRF1) OTOXWNV8 NRF1_HUMAN Decreases Expression [29]
Natural cytotoxicity triggering receptor 3 ligand 1 (NCR3LG1) OT15YWU7 NR3L1_HUMAN Increases Expression [30]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [26]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) OTHCDQ22 PRGC1_HUMAN Decreases Expression [29]
Arylamine N-acetyltransferase 2 (NAT2) OTBPDQOY ARY2_HUMAN Decreases Acetylation [31]
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⏷ 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
Adult acute myeloid leukemia DC8ZEPY HL-60(TB) Investigative [1]
Adult T acute lymphoblastic leukemia DCNL966 MOLT-4 Investigative [1]
Colon carcinoma DC11IQ8 KM12 Investigative [32]
Adenocarcinoma DCOD4LF HCC-2998 Investigative [33]
High grade ovarian serous adenocarcinoma DCXM42T NCI\\/ADR-RES Investigative [33]
Non-small cell lung carcinoma DC0QV5A HOP-92 Investigative [33]
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⏷ Show the Full List of 6 DrugCom(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Mechlorethamine FDA Label
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 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: 7218).
5 Isoniazid FDA Label
6 Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.
7 Thioredoxin Cross-Linking by Nitrogen Mustard in Lung Epithelial Cells: Formation of Multimeric Thioredoxin/Thioredoxin Reductase Complexes and Inhibition of Disulfide Reduction. Chem Res Toxicol. 2015 Nov 16;28(11):2091-103. doi: 10.1021/acs.chemrestox.5b00194. Epub 2015 Oct 19.
8 Cross-linking of thioredoxin reductase by the sulfur mustard analogue mechlorethamine (methylbis(2-chloroethyl)amine) in human lung epithelial cells and rat lung: selective inhibition of disulfide reduction but not redox cycling. Chem Res Toxicol. 2014 Jan 21;27(1):61-75. doi: 10.1021/tx400329a. Epub 2013 Dec 9.
9 Proteomic analysis of DNA-protein cross-linking by antitumor nitrogen mustards. Chem Res Toxicol. 2009 Jun;22(6):1151-62.
10 Down-regulation of HER-2 expression in human breast cancer cell HBC-4 and ZR75-1 by nitrogen-mustard-N-oxide. Kobe J Med Sci. 2007;53(4):135-42.
11 Nitrogen mustard prevents transport of Fra-1 into the nucleus to promote c-Fos- and FosB-dependent IL-8 induction in injured mouse epidermis. Toxicol Lett. 2020 Feb 1;319:256-263. doi: 10.1016/j.toxlet.2019.10.006. Epub 2019 Oct 19.
12 S100P is selectively upregulated in tumor cell lines challenged with DNA cross-linking agents. Leuk Res. 2005 Oct;29(10):1181-90. doi: 10.1016/j.leukres.2005.03.012.
13 Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard. Am J Dermatopathol. 1998 Feb;20(1):22-8. doi: 10.1097/00000372-199802000-00005.
14 Increased expression of VDAC1 sensitizes carcinoma cells to apoptosis induced by DNA cross-linking agents. Biochem Pharmacol. 2012 May 1;83(9):1172-82. doi: 10.1016/j.bcp.2012.01.017. Epub 2012 Jan 21.
15 Activation of the human TRPA1 channel by different alkylating sulfur and nitrogen mustards and structurally related chemotherapeutic drugs. Toxicol Lett. 2023 Mar 1;376:51-59. doi: 10.1016/j.toxlet.2023.01.007. Epub 2023 Jan 21.
16 Characterization of drug-specific signaling between primary human hepatocytes and immune cells. Toxicol Sci. 2017 Jul 1;158(1):76-89.
17 Diversity in enoyl-acyl carrier protein reductases. Cell Mol Life Sci. 2009 May;66(9):1507-17.
18 Inhibition of CYP2E1 catalytic activity in vitro by S-adenosyl-L-methionine. Biochem Pharmacol. 2005 Apr 1;69(7):1081-93.
19 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.
20 The actinobacterium Tsukamurella paurometabola has a functionally divergent arylamine N-acetyltransferase (NAT) homolog. World J Microbiol Biotechnol. 2019 Oct 31;35(11):174.
21 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.
22 Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
23 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.
24 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.
25 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.
26 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.
27 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.
28 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.
29 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.
30 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.
31 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.
32 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
33 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976