Details of the Drug Combination

General Information of Drug Combination (ID: DC83WGN)

Drug Combination Name
Triapine Raloxifene
Indication
Disease Entry Status REF
Invasive ductal carcinoma Investigative [1]
Component Drugs Triapine   DM7XZY5 Raloxifene   DMDKF3M
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: T-47D
Zero Interaction Potency (ZIP) Score: 0.89
Bliss Independence Score: 4.08
Loewe Additivity Score: 0.01
LHighest Single Agent (HSA) Score: 1.31

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 [5]
Thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) OTLB2WEU PRDX3_HUMAN Increases Oxidation [4]
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Indication(s) of Raloxifene
Disease Entry ICD 11 Status REF
Osteoporosis FB83.0 Approved [3]
Raloxifene Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Estrogen receptor (ESR) TTZAYWL ESR1_HUMAN Modulator [6]
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Raloxifene Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
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Raloxifene Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [9]
UDP-glucuronosyltransferase 1A10 (UGT1A10) DEL5N6Y UD110_HUMAN Metabolism [10]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DCDE6SL OVCAR3 Investigative [11]
Cutaneous melanoma DCL50BP SK-MEL-5 Investigative [11]
High grade ovarian serous adenocarcinoma DC2QIRL OVCAR-5 Investigative [11]
Lung adenocarcinoma DCX67D4 EKVX Investigative [11]
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References

1 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.
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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 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.
5 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.
6 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. (Target id: 620).
7 Influence of hepatic and intestinal efflux transporters and their genetic variants on the pharmacokinetics and pharmacodynamics of raloxifene in osteoporosis treatment. Transl Res. 2012 Oct;160(4):298-308.
8 The role of P-glycoprotein in the bioactivation of raloxifene. Drug Metab Dispos. 2006 Dec;34(12):2073-8.
9 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
10 Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo. Cancer Prev Res (Phila). 2013 Jul;6(7):719-30.
11 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.