General Information of Drug Combination (ID: DCDG949)

Drug Combination Name
Bosentan Triapine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Bosentan   DMIOGBU Triapine   DM7XZY5
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: 3.58
Bliss Independence Score: 3.58
Loewe Additivity Score: 4.41
LHighest Single Agent (HSA) Score: 4.41

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Bosentan
Disease Entry ICD 11 Status REF
Pulmonary arterial hypertension BB01.0 Approved [2]
Pulmonary hypertension BB01 Approved [3]
Scleroderma 4A42 Investigative [3]
Bosentan Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Endothelin A receptor (EDNRA) TTKRD0G EDNRA_HUMAN Modulator [6]
Endothelin B receptor (EDNRB) TT3ZTGU EDNRB_HUMAN Modulator [6]
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Bosentan Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [7]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [7]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [7]
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Bosentan Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [9]
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Bosentan Interacts with 71 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [10]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Decreases Expression [5]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Expression [5]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Activity [11]
Nitric oxide synthase 3 (NOS3) OTLDT7NR NOS3_HUMAN Increases ADR [12]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Expression [10]
Serine/threonine-protein kinase DCLK1 (DCLK1) OTVSPS98 DCLK1_HUMAN Affects Expression [5]
Kynurenine 3-monooxygenase (KMO) OT3MRMM9 KMO_HUMAN Affects Expression [5]
Carbonic anhydrase 12 (CA12) OT6WNFU8 CAH12_HUMAN Affects Expression [5]
All-trans-retinol dehydrogenase ADH1B (ADH1B) OTV3TB81 ADH1B_HUMAN Decreases Expression [5]
Alcohol dehydrogenase 1C (ADH1C) OTO1DV7F ADH1G_HUMAN Decreases Expression [5]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Decreases Expression [5]
Complement component C9 (C9) OT7I5FDX CO9_HUMAN Affects Expression [5]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Expression [5]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [5]
Insulin-like growth factor I (IGF1) OTIIZR61 IGF1_HUMAN Affects Expression [5]
Fructose-bisphosphate aldolase B (ALDOB) OT7FR69A ALDOB_HUMAN Decreases Expression [5]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [5]
Fatty acid-binding protein, liver (FABP1) OTR34ETM FABPL_HUMAN Decreases Expression [5]
Glutathione peroxidase 1 (GPX1) OTE2O72Q GPX1_HUMAN Decreases Expression [5]
Alcohol dehydrogenase 1A (ADH1A) OTTS983E ADH1A_HUMAN Decreases Expression [5]
Amino acid transporter heavy chain SLC3A2 (SLC3A2) OTBR33M9 4F2_HUMAN Increases Expression [5]
All-trans-retinol dehydrogenase ADH4 (ADH4) OTKDKKNG ADH4_HUMAN Decreases Expression [5]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [5]
Glutathione S-transferase theta-2 (GSTT2) OTANW3TJ GST2_HUMAN Decreases Expression [5]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [5]
Microsomal glutathione S-transferase 1 (MGST1) OTGN1KVZ MGST1_HUMAN Decreases Expression [5]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1) OTNAZVKB 3BHS1_HUMAN Affects Expression [5]
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Increases Expression [5]
NADPH--cytochrome P450 reductase (POR) OTVIDOCH NCPR_HUMAN Affects Expression [5]
Tyrosine aminotransferase (TAT) OT2CJ91O ATTY_HUMAN Affects Expression [5]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Expression [5]
Cytochrome P450 7A1 (CYP7A1) OT8Z5KLD CP7A1_HUMAN Decreases Expression [5]
Macrophage mannose receptor 1 (MRC1) OTTVCOPT MRC1_HUMAN Affects Expression [5]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Affects Expression [5]
Serum paraoxonase/arylesterase 1 (PON1) OTD0Z2XO PON1_HUMAN Decreases Expression [5]
G0/G1 switch protein 2 (G0S2) OT8FL49L G0S2_HUMAN Affects Expression [5]
Sodium- and chloride-dependent GABA transporter 1 (SLC6A1) OTLCJJF3 SC6A1_HUMAN Affects Expression [5]
Pyruvate kinase PKLR (PKLR) OTTTM1QI KPYR_HUMAN Affects Expression [5]
Carbamoyl-phosphate synthase , mitochondrial (CPS1) OTXV8NSR CPSM_HUMAN Decreases Expression [5]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1) OTJ6FM9F G6PC1_HUMAN Affects Expression [5]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Expression [5]
Hepatocyte nuclear factor 4-alpha (HNF4A) OTY1TOAB HNF4A_HUMAN Decreases Expression [5]
Glutamate--cysteine ligase catalytic subunit (GCLC) OTESDI4D GSH1_HUMAN Increases Expression [5]
Sulfotransferase 1E1 (SULT1E1) OTGPJ517 ST1E1_HUMAN Affects Expression [5]
Achaete-scute homolog 1 (ASCL1) OTI4X44G ASCL1_HUMAN Affects Expression [5]
Oxysterols receptor LXR-beta (NR1H2) OT4APA60 NR1H2_HUMAN Decreases Expression [5]
Microsomal triglyceride transfer protein large subunit (MTTP) OTNUVSDT MTP_HUMAN Decreases Expression [5]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Affects Expression [5]
Metallothionein-1X (MT1X) OT9AKFVS MT1X_HUMAN Increases Expression [5]
Complement factor H-related protein 3 (CFHR3) OTYL8SDO FHR3_HUMAN Affects Expression [5]
Oxysterols receptor LXR-alpha (NR1H3) OT54YZ9I NR1H3_HUMAN Decreases Expression [5]
Nuclear factor 1 X-type (NFIX) OT1DPZAE NFIX_HUMAN Decreases Expression [5]
Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2) OTJ8LX4N PCKGM_HUMAN Decreases Expression [5]
Organic solute transporter subunit alpha (SLC51A) OTDJRZ0P OSTA_HUMAN Increases Expression [5]
Organic solute transporter subunit beta (SLC51B) OT4WYPSR OSTB_HUMAN Increases Expression [5]
Liver-expressed antimicrobial peptide 2 (LEAP2) OTUOPIS5 LEAP2_HUMAN Affects Expression [5]
N-acetylmuramoyl-L-alanine amidase (PGLYRP2) OTF8319A PGRP2_HUMAN Affects Expression [5]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Decreases Expression [5]
Normal mucosa of esophagus-specific gene 1 protein (C15ORF48) OT85J32K NMES1_HUMAN Affects Expression [5]
ATP-binding cassette sub-family G member 5 (ABCG5) OT1OMY93 ABCG5_HUMAN Affects Expression [5]
2-aminomuconic semialdehyde dehydrogenase (ALDH8A1) OTINY3MW AL8A1_HUMAN Affects Expression [5]
Cytochrome P450 3A43 (CYP3A43) OTMXADGA CP343_HUMAN Affects Expression [5]
NADPH oxidase 4 (NOX4) OTTYQ097 NOX4_HUMAN Decreases Expression [5]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) OTHCDQ22 PRGC1_HUMAN Decreases Expression [5]
Solute carrier family 22 member 7 (SLC22A7) OTKTNH1W S22A7_HUMAN Affects Expression [5]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Decreases Expression [13]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Expression [13]
Coxsackievirus and adenovirus receptor (CXADR) OT9ZP02A CXAR_HUMAN Decreases Expression [14]
Hepatic sodium/bile acid cotransporter (SLC10A1) OTUJVMCL NTCP_HUMAN Decreases Expression [13]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Decreases Expression [13]
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⏷ Show the Full List of 71 DOT(s)
Indication(s) of Triapine
Disease Entry ICD 11 Status REF
Nerve injury ND56.4 Phase 2 [4]
Triapine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Ribonucleoside-diphosphate reductase M2 (RRM2) TTBWDI0 RIR2_HUMAN Modulator [4]
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Triapine Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [16]
Thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) OTLB2WEU PRDX3_HUMAN Increases Oxidation [15]
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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 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: 3494).
3 Bosentan FDA Label
4 PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species. J Alzheimers Dis. 2009;17(3):611-9.
5 Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7 Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007 Aug;35(8):1400-7.
8 Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007 Aug;35(8):1400-7.
9 Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Clin Pharmacokinet. 2003;42(3):293-301.
10 Comparison of immortalized Fa2N-4 cells and human hepatocytes as in vitro models for cytochrome P450 induction. Drug Metab Dispos. 2008 Jun;36(6):1046-55.
11 ?-adrenoceptors and muscarinic receptors mediate opposing effects on endothelin-1 expression in human lung fibroblasts. Eur J Pharmacol. 2012 Sep 15;691(1-3):218-24. doi: 10.1016/j.ejphar.2012.07.002. Epub 2012 Jul 13.
12 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.
13 From the Cover: MechanisticInsights in Cytotoxic and Cholestatic Potential of the Endothelial Receptor Antagonists Using HepaRG Cells. Toxicol Sci. 2017 Jun 1;157(2):451-464. doi: 10.1093/toxsci/kfx062.
14 Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells. J Gen Virol. 2010 Aug;91(Pt 8):1959-1970. doi: 10.1099/vir.0.020065-0. Epub 2010 Apr 14.
15 The iron-chelating drug triapine causes pronounced mitochondrial thiol redox stress. Toxicol Lett. 2011 Mar 5;201(2):130-6. doi: 10.1016/j.toxlet.2010.12.017. Epub 2010 Dec 31.
16 Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes. Biochem Pharmacol. 2014 Oct 1;91(3):312-22. doi: 10.1016/j.bcp.2014.08.006. Epub 2014 Aug 15.