Details of the Drug Combination

General Information of Drug Combination (ID: DCTFFT1)

Drug Combination Name
TRIENTINE Carboplatin
Indication
Disease Entry Status REF
Advanced Cancers Phase 1 [1]
Component Drugs TRIENTINE   DMD2WPG Carboplatin   DMG281S
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of TRIENTINE
Disease Entry ICD 11 Status REF
Inborn error of metabolism 5C50-5C59 Approved [2]
Wilson disease 5C64.00 Investigative [3]
TRIENTINE Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Carbonic anhydrase XIV (CA-XIV) TTEYTKG CAH14_HUMAN Inhibitor [6]
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TRIENTINE Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Decreases Activity [7]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Phosphorylation [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [7]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [7]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [8]
High affinity copper uptake protein 1 (SLC31A1) OTXLRTUB COPT1_HUMAN Increases Expression [9]
Amyloid-beta precursor protein (APP) OTKFD7R4 A4_HUMAN Decreases Expression [10]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [11]
Beta-secretase 1 (BACE1) OTCA7B6A BACE1_HUMAN Decreases Expression [10]
Advanced glycosylation end product-specific receptor (AGER) OTPY0IH7 RAGE_HUMAN Decreases Expression [10]
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⏷ Show the Full List of 10 DOT(s)
Indication(s) of Carboplatin
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [4]
Carcinoma 2A00-2F9Z Approved [4]
Cholangiocarcinoma 2C12.10 Approved [4]
Cutaneous melanoma 2C30 Approved [4]
Epithelial ovarian cancer 2B5D Approved [4]
Fallopian tube neoplasm N.A. Approved [4]
Gastroesophageal junction adenocarcinoma 2B71 Approved [4]
Lung adenocarcinoma N.A. Approved [4]
Lung cancer 2C25.0 Approved [4]
Non-small-cell lung cancer 2C25.Y Approved [4]
Ovarian cancer 2C73 Approved [5]
Ovarian disorder N.A. Approved [4]
Ovarian neoplasm N.A. Approved [4]
Ovarian serous cystadenocarcinoma N.A. Approved [4]
Small-cell lung cancer 2C25.Y Approved [4]
Lung large cell carcinoma N.A. Investigative [4]
Neuroblastoma 2D11.2 Investigative [4]
Carboplatin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [12]
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Carboplatin Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
High affinity copper uptake protein 1 (SLC31A1) DTP8L4F COPT1_HUMAN Substrate [13]
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Carboplatin Interacts with 7 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Glutathione S-transferase pi (GSTP1) DEK6079 GSTP1_HUMAN Metabolism [14]
Glutathione S-transferase theta-1 (GSTT1) DE3PKUG GSTT1_HUMAN Metabolism [14]
Metallothionein-1A (MT1A) DE5ME8A MT1A_HUMAN Metabolism [14]
Metallothionein-2A (MT2A) DEFKGT7 MT2_HUMAN Metabolism [14]
Myeloperoxidase (MPO) DEA3U9Y PERM_HUMAN Metabolism [14]
Quinone reductase 1 (NQO1) DENP5RY NQO1_HUMAN Metabolism [14]
Glutathione S-transferase mu-1 (GSTM1) DEYZEJA GSTM1_HUMAN Metabolism [14]
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⏷ Show the Full List of 7 DME(s)

References

1 ClinicalTrials.gov (NCT01178112) Trientine and Carboplatin in Advanced Malignancies
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Trientine FDA Label
4 Carboplatin FDA Label
5 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: 7624).
6 Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22.
7 Increased susceptibility of copper-deficient neuroblastoma cells to oxidative stress-mediated apoptosis. Free Radic Biol Med. 2001 May 15;30(10):1177-87.
8 Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells. Cell Mol Life Sci. 2003 Aug;60(8):1733-43.
9 Mechanistic basis for overcoming platinum resistance using copper chelating agents. Mol Cancer Ther. 2012 Nov;11(11):2483-94. doi: 10.1158/1535-7163.MCT-12-0580. Epub 2012 Aug 21.
10 Trientine reduces BACE1 activity and mitigates amyloidosis via the AGE/RAGE/NF-B pathway in a transgenic mouse model of Alzheimer's disease. Antioxid Redox Signal. 2013 Dec 10;19(17):2024-39. doi: 10.1089/ars.2012.5158. Epub 2013 May 3.
11 The copper chelator trientine has an antiangiogenic effect against hepatocellular carcinoma, possibly through inhibition of interleukin-8 production. Int J Cancer. 2002 Dec 10;102(5):445-52. doi: 10.1002/ijc.10740.
12 Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer.Clin Cancer Res.2010 Oct 1;16(19):4899-905.
13 Overcoming platinum drug resistance with copper-lowering agents. Anticancer Res. 2013 Oct;33(10):4157-61.
14 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)