Details of the Drug Combination

General Information of Drug Combination (ID: DCZEG0I)

Drug Combination Name
Ramelteon Triapine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Ramelteon   DM7IW9J 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: 3.57
Bliss Independence Score: 3.57
Loewe Additivity Score: 4.31
LHighest Single Agent (HSA) Score: 4.31

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Ramelteon
Disease Entry ICD 11 Status REF
Insomnia 7A00-7A0Z Approved [2]
Circadian rhythm sleep disorder 7A60-7A65 Terminated [2]
Ramelteon Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Melatonin receptor type 1B (MTNR1B) TT32JK8 MTR1B_HUMAN Modulator [5]
Melatonin receptor type 1A (MTNR1A) TT0WAIE MTR1A_HUMAN Modulator [5]
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Ramelteon Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [6]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [6]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [7]
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Ramelteon Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Retinal dehydrogenase 2 (ALDH1A2) OTJB560Z AL1A2_HUMAN Decreases Expression [4]
Homeobox protein Hox-B7 (HOXB7) OTC7WYU8 HXB7_HUMAN Increases Expression [4]
Paired box protein Pax-6 (PAX6) OTOC9876 PAX6_HUMAN Decreases Expression [4]
Homeobox protein MOX-1 (MEOX1) OTJEMT2D MEOX1_HUMAN Decreases Expression [4]
Fibroblast growth factor 8 (FGF8) OTFU0IUW FGF8_HUMAN Decreases Expression [4]
Mesoderm posterior protein 2 (MESP2) OT7H4LYA MESP2_HUMAN Increases Expression [4]
Oligodendrocyte transcription factor 3 (OLIG3) OTU8XLAF OLIG3_HUMAN Decreases Expression [4]
Eyes absent homolog 1 (EYA1) OTHU807A EYA1_HUMAN Decreases Expression [4]
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⏷ Show the Full List of 8 DOT(s)
Indication(s) of Triapine
Disease Entry ICD 11 Status REF
Nerve injury ND56.4 Phase 2 [3]
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 [3]
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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 [9]
Thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) OTLB2WEU PRDX3_HUMAN Increases Oxidation [8]
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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: 1356).
3 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.
4 Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
5 MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 2014 Apr 24;57(8):3161-85.
6 Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. Drug Metab Dispos. 2010 Aug;38(8):1381-91.
7 Pharmacotherapy of insomnia with ramelteon: safety, efficacy and clinical applications. J Cent Nerv Syst Dis. 2011 Apr 12;3:51-65.
8 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.
9 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.