General Information of Drug Combination (ID: DC5X0MU)

Drug Combination Name
Picoplatin Isoniazid
Indication
Disease Entry Status REF
Childhood T acute lymphoblastic leukemia Investigative [1]
Component Drugs Picoplatin   DM0PIY6 Isoniazid   DM5JVS3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: CCRF-CEM
Zero Interaction Potency (ZIP) Score: 5.79
Bliss Independence Score: 5.6
Loewe Additivity Score: 3.15
LHighest Single Agent (HSA) Score: 1.82

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Picoplatin
Disease Entry ICD 11 Status REF
Colorectal cancer 2B91.Z Phase 3 [2]
Ovarian cancer 2C73 Phase 3 [2]
Prostate cancer 2C82.0 Phase 3 [2]
Small-cell lung cancer 2C25.Y Phase 3 [2]
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 [6]
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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 [7]
Catalase-peroxidase (katG) DEAGY5M KATG_SYNE7 Metabolism [8]
Arylamine N-acetyltransferase (NAT) DEXCQTM A0A3P8LE58_TSUPA Metabolism [9]
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Isoniazid Interacts with 59 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Expression [10]
N-alpha-acetyltransferase 20 (NAA20) OTJB0VA6 NAA20_HUMAN Increases ADR [11]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Decreases Activity [12]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [13]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [13]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [13]
Aldo-keto reductase family 1 member B10 (AKR1B10) OTOA4HTH AK1BA_HUMAN Increases Expression [5]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Secretion [5]
Interferon gamma (IFNG) OTXG9JM7 IFNG_HUMAN Increases Secretion [5]
C-X-C motif chemokine 10 (CXCL10) OTTLQ6S0 CXL10_HUMAN Increases Secretion [5]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Secretion [5]
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Increases Expression [5]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [5]
Interleukin-12 subunit alpha (IL12A) OTDQT8GI IL12A_HUMAN Increases Secretion [5]
Interleukin-12 subunit beta (IL12B) OT0JF8A3 IL12B_HUMAN Increases Secretion [5]
Interleukin-17A (IL17A) OTY72FT2 IL17_HUMAN Increases Secretion [5]
Sulfiredoxin-1 (SRXN1) OTYDBO4L SRXN1_HUMAN Increases Expression [5]
Gamma-butyrobetaine dioxygenase (BBOX1) OTKEX4RK BODG_HUMAN Increases Expression [14]
Alpha-fetoprotein (AFP) OT9GG3ZI FETA_HUMAN Decreases Expression [14]
Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1) OTTO6ZP4 AT1B1_HUMAN Increases Expression [14]
Amyloid-beta precursor protein (APP) OTKFD7R4 A4_HUMAN Increases Expression [14]
Osteopontin (SPP1) OTJGC23Y OSTP_HUMAN Decreases Expression [14]
Mucin-1 (MUC1) OTHQI7IY MUC1_HUMAN Increases Expression [14]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Decreases Expression [14]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Decreases Expression [14]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Decreases Expression [14]
Claudin-2 (CLDN2) OTRF3D6Y CLD2_HUMAN Increases Expression [14]
Large neutral amino acids transporter small subunit 1 (SLC7A5) OT2WPVXD LAT1_HUMAN Decreases Expression [14]
Tribbles homolog 3 (TRIB3) OTG5OS7X TRIB3_HUMAN Increases Expression [14]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) OTKOZRZP PLOD2_HUMAN Increases Expression [15]
Transmembrane protease serine 2 (TMPRSS2) OTN44YQ5 TMPS2_HUMAN Affects Expression [16]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [17]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [17]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [18]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [17]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Activity [19]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [19]
Glucose-6-phosphate 1-dehydrogenase (G6PD) OT300SMK G6PD_HUMAN Decreases Activity [19]
5-aminolevulinate synthase, non-specific, mitochondrial (ALAS1) OTQY6ZSF HEM1_HUMAN Increases Expression [20]
Ferrochelatase, mitochondrial (FECH) OTDWEI6C HEMH_HUMAN Decreases Expression [20]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [10]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [17]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Expression [21]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [19]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [19]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [10]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [17]
Nuclear respiratory factor 1 (NRF1) OTOXWNV8 NRF1_HUMAN Decreases Expression [22]
Natural cytotoxicity triggering receptor 3 ligand 1 (NCR3LG1) OT15YWU7 NR3L1_HUMAN Increases Expression [23]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [17]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1) OTAYZMOY SIR1_HUMAN Decreases Expression [22]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Decreases Expression [16]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) OTHCDQ22 PRGC1_HUMAN Decreases Expression [22]
Arylamine N-acetyltransferase 2 (NAT2) OTBPDQOY ARY2_HUMAN Decreases Acetylation [24]
Eosinophil peroxidase (EPX) OTFNDFOK PERE_HUMAN Increases Oxidation [25]
Myeloperoxidase (MPO) OTOOXLIN PERM_HUMAN Increases Oxidation [26]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Response To Substance [27]
Glutathione S-transferase Mu 1 (GSTM1) OTSBF2MO GSTM1_HUMAN Decreases Response To Substance [28]
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⏷ Show the Full List of 59 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Astrocytoma DC7ESHP U251 Investigative [1]
Clear cell renal cell carcinoma DCC74TI CAKI-1 Investigative [1]
Glioblastoma DCVXE2B SNB-75 Investigative [1]
Colon carcinoma DCC3OKL KM12 Investigative [29]
High grade ovarian serous adenocarcinoma DCNXCJL NCI\\/ADR-RES Investigative [30]
Minimally invasive lung adenocarcinoma DC9P4L2 NCI-H322M Investigative [30]
Mixed endometrioid and clear cell carcinoma DC8HXMK IGROV1 Investigative [30]
Non-small cell lung carcinoma DC4GUNG HOP-92 Investigative [30]
Pleural epithelioid mesothelioma DCEMKB3 NCI-H226 Investigative [30]
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⏷ Show the Full List of 9 DrugCom(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 ClinicalTrials.gov (NCT00465491) Study of Picoplatin Efficacy After Relapse. U.S. National Institutes of Health.
3 Isoniazid FDA Label
4 Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.
5 Characterization of drug-specific signaling between primary human hepatocytes and immune cells. Toxicol Sci. 2017 Jul 1;158(1):76-89.
6 Diversity in enoyl-acyl carrier protein reductases. Cell Mol Life Sci. 2009 May;66(9):1507-17.
7 Inhibition of CYP2E1 catalytic activity in vitro by S-adenosyl-L-methionine. Biochem Pharmacol. 2005 Apr 1;69(7):1081-93.
8 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.
9 The actinobacterium Tsukamurella paurometabola has a functionally divergent arylamine N-acetyltransferase (NAT) homolog. World J Microbiol Biotechnol. 2019 Oct 31;35(11):174.
10 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.
11 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.
12 Mechanism-based inactivation of human cytochrome P4502C8 by drugs in vitro. J Pharmacol Exp Ther. 2004 Dec;311(3):996-1007.
13 Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
14 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.
15 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.
16 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.
17 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.
18 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.
19 Isoniazid-induced apoptosis in HepG2 cells: generation of oxidative stress and Bcl-2 down-regulation. Toxicol Mech Methods. 2010 Jun;20(5):242-51. doi: 10.3109/15376511003793325.
20 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.
21 Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes. Toxicol Appl Pharmacol. 2013 Dec 15;273(3):435-41. doi: 10.1016/j.taap.2013.10.005. Epub 2013 Oct 12.
22 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.
23 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.
24 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.
25 Eosinophil peroxidase oxidizes isoniazid to form the active metabolite against M. tuberculosis, isoniazid-NAD(). Chem Biol Interact. 2019 May 25;305:48-53. doi: 10.1016/j.cbi.2019.03.019. Epub 2019 Mar 25.
26 Metabolism of isoniazid by neutrophil myeloperoxidase leads to isoniazid-NAD(+) adduct formation: A comparison of the reactivity of isoniazid with its known human metabolites. Biochem Pharmacol. 2016 Apr 15;106:46-55. doi: 10.1016/j.bcp.2016.02.003. Epub 2016 Feb 9.
27 Development of a highly sensitive cytotoxicity assay system for CYP3A4-mediated metabolic activation. Drug Metab Dispos. 2011 Aug;39(8):1388-95. doi: 10.1124/dmd.110.037077. Epub 2011 May 3.
28 Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury. Arch Toxicol. 2018 Jan;92(1):383-399. doi: 10.1007/s00204-017-2036-4. Epub 2017 Jul 31.
29 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
30 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.