Details of the Drug Combination

General Information of Drug Combination (ID: DCTTEZ2)

Drug Combination Name
Triapine Zaleplon
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Triapine   DM7XZY5 Zaleplon   DMGFWSM
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: 1.99
Bliss Independence Score: 1.99
Loewe Additivity Score: 2.57
LHighest Single Agent (HSA) Score: 2.57

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Triapine
Disease Entry ICD 11 Status REF
Nerve injury ND56.4 Phase 2 [2]
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 [2]
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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 [6]
Thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) OTLB2WEU PRDX3_HUMAN Increases Oxidation [5]
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Indication(s) of Zaleplon
Disease Entry ICD 11 Status REF
Insomnia 7A00-7A0Z Approved [3]
Sleep disorder, initiating and maintaining sleep N.A. Investigative [4]
Zaleplon Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
GABA(A) receptor alpha-1 (GABRA1) TT1MPAY GBRA1_HUMAN Modulator [7]
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Zaleplon Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [9]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [9]
Aldehyde oxidase (AOX1) DEAWHS8 AOXA_HUMAN Metabolism [10]
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References

1 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.
2 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.
3 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: 4345).
4 Zaleplon FDA Label
5 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.
6 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.
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
8 Metabolism of zaleplon by human liver: evidence for involvement of aldehyde oxidase. Xenobiotica. 2002 Oct;32(10):835-47.
9 Drug Interactions Flockhart Table
10 Characterization of aldehyde oxidase enzyme activity in cryopreserved human hepatocytes. Drug Metab Dispos. 2012 Feb;40(2):267-75.