General Information of Drug Combination (ID: DC21ZO9)

Drug Combination Name
Triapine Pomalidomide
Indication
Disease Entry Status REF
Large cell lung carcinoma Investigative [1]
Component Drugs Triapine   DM7XZY5 Pomalidomide   DMTGBAX
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: NCI-H460
Zero Interaction Potency (ZIP) Score: 1.33
Bliss Independence Score: 1.93
Loewe Additivity Score: 1.05
LHighest Single Agent (HSA) Score: 0.5

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 Pomalidomide
Disease Entry ICD 11 Status REF
Plasma cell myeloma 2A83.1 Approved [3]
Systemic sclerosis 4A42 Approved [4]
Pomalidomide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Angiogenesis/myeloma cell growth (AMCG) TTDIBYJ NOUNIPROTAC Modulator [7]
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Pomalidomide 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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Pomalidomide Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [10]
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Pomalidomide Interacts with 27 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Oxidation [11]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Decreases Secretion [12]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Secretion [12]
Granulocyte colony-stimulating factor (CSF3) OT9GC6TP CSF3_HUMAN Increases Secretion [12]
Fibroblast growth factor receptor 1 (FGFR1) OT4GLCXW FGFR1_HUMAN Decreases Expression [13]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Secretion [12]
Erythroid transcription factor (GATA1) OTX1R7O1 GATA1_HUMAN Decreases Expression [12]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Decreases Expression [12]
Transcription factor PU.1 (SPI1) OTVCA1D0 SPI1_HUMAN Increases Expression [12]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [12]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Affects Expression [13]
Endothelial transcription factor GATA-2 (GATA2) OTBP2QQ2 GATA2_HUMAN Decreases Expression [12]
Rhombotin-2 (LMO2) OTCC370G RBTN2_HUMAN Decreases Expression [12]
Interleukin-13 (IL13) OTI4YS3Y IL13_HUMAN Decreases Secretion [12]
DNA-binding protein inhibitor ID-1 (ID1) OTKGNZN5 ID1_HUMAN Increases Expression [12]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Increases Expression [12]
CCAAT/enhancer-binding protein delta (CEBPD) OTNBIPMY CEBPD_HUMAN Increases Expression [12]
DNA-binding protein inhibitor ID-2 (ID2) OT0U1D53 ID2_HUMAN Increases Expression [12]
Krueppel-like factor 1 (KLF1) OT1FK08U KLF1_HUMAN Decreases Expression [12]
CCAAT/enhancer-binding protein epsilon (CEBPE) OTKZA25M CEBPE_HUMAN Increases Expression [12]
Transcription factor NF-E2 45 kDa subunit (NFE2) OTLM94BI NFE2_HUMAN Decreases Expression [12]
Zinc finger protein Gfi-1b (GFI1B) OTRDW8YO GFI1B_HUMAN Decreases Expression [12]
Zinc finger protein Gfi-1 (GFI1) OT9HB9H8 GFI1_HUMAN Increases Expression [12]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Affects Binding [14]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Oxidation [11]
Cytochrome P450 2J2 (CYP2J2) OTJBTEH8 CP2J2_HUMAN Increases Oxidation [11]
Protein cereblon (CRBN) OTXH9MDC CRBN_HUMAN Increases Response To Substance [15]
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⏷ Show the Full List of 27 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Invasive ductal carcinoma DCX6ZT8 T-47D Investigative [16]
Astrocytoma DCG056I U251 Investigative [1]
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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 Pomalidomide FDA Label
4 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: 7348).
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 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
8 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB08910)
9 Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78.
10 Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72.
11 Human cytochrome P450 oxidation of 5-hydroxythalidomide and pomalidomide, an amino analogue of thalidomide. Chem Res Toxicol. 2014 Jan 21;27(1):147-56. doi: 10.1021/tx4004215. Epub 2013 Dec 24.
12 Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis. Blood. 2005 May 15;105(10):3833-40. doi: 10.1182/blood-2004-03-0828. Epub 2004 Aug 3.
13 Thalidomide and Its Analogs Differentially Target Fibroblast Growth Factor Receptors: Thalidomide Suppresses FGFR Gene Expression while Pomalidomide Dampens FGFR2 Activity. Chem Res Toxicol. 2019 Apr 15;32(4):589-602. doi: 10.1021/acs.chemrestox.8b00286. Epub 2019 Mar 15.
14 Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. Elife. 2018 Aug 1;7:e38430. doi: 10.7554/eLife.38430.
15 A Dual Color Immunohistochemistry Assay for Measurement of Cereblon in Multiple Myeloma Patient Samples. Appl Immunohistochem Mol Morphol. 2016 Nov/Dec;24(10):695-702. doi: 10.1097/PAI.0000000000000246.
16 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.