General Information of Drug Combination (ID: DCGB3QB)

Drug Combination Name
Triapine Pralatrexate
Indication
Disease Entry Status REF
Carcinoma Investigative [1]
Component Drugs Triapine   DM7XZY5 Pralatrexate   DMAO80I
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: MCF7
Zero Interaction Potency (ZIP) Score: 0.23
Bliss Independence Score: 1.49
Loewe Additivity Score: 0.66
LHighest Single Agent (HSA) Score: 0.12

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 Pralatrexate
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [3]
Peripheral T-cell lymphoma 2A90.C Approved [3]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [4]
Pralatrexate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Polypeptide deformylase (PDF) TT9SL3Q DEFM_HUMAN Inhibitor [7]
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Pralatrexate Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Folate transporter 1 (SLC19A1) DTOSN46 S19A1_HUMAN Substrate [8]
Proton-coupled folate transporter (SLC46A1) DTDJEMI PCFT_HUMAN Substrate [8]
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Pralatrexate Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Folylpolyglutamate synthase (FPGS) DECWT2V FOLC_HUMAN Metabolism [9]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DC9LHB9 DU-145 Investigative [10]
Adenocarcinoma DCDQ46O HCT-15 Investigative [10]
Childhood T acute lymphoblastic leukemia DC2IEP5 CCRF-CEM Investigative [10]
Glioblastoma DCQWRIK SNB-75 Investigative [10]
Glioma DCIPBR6 SF-539 Investigative [10]
Melanoma DCS0QFV SK-MEL-2 Investigative [10]
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⏷ Show the Full List of 6 DrugCom(s)

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 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: 6840).
4 Pralatrexate 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 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
8 Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210.
9 Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma. Expert Opin Pharmacother. 2013 Mar;14(4):515-23.
10 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.