Details of the Drug Combination

General Information of Drug Combination (ID: DCXKU4D)

Drug Combination Name
Triapine Guanfacine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Triapine   DM7XZY5 Guanfacine   DMPN5IH
Small molecular drug N.A.
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 1.05
Bliss Independence Score: 1.05
Loewe Additivity Score: 1.69
LHighest Single Agent (HSA) Score: 1.69

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 Guanfacine
Disease Entry ICD 11 Status REF
Attention deficit hyperactivity disorder 6A05.Z Approved [3]
Alzheimer disease 8A20 Phase 3 [4]
Guanfacine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor alpha-2A (ADRA2A) TTWG9A4 ADA2A_HUMAN Agonist [7]
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Guanfacine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
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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 Guanfacine FDA Label
4 ClinicalTrials.gov (NCT03116126) Randomised Clinical Trial of Noradrenergic Add-on Therapy With Extended-Release Guanfacine in Alzheimer's Disease. U.S.National Institutes of Health.
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 Scientific rationale for the use of alpha2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders. Mol Psychiatry. 2023 Apr 7:1-13.
8 An in vitro evaluation of guanfacine as a substrate for P-glycoprotein. Neuropsychiatr Dis Treat. 2011;7:501-5.