Details of the Drug Combination

General Information of Drug Combination (ID: DCMZ702)

Drug Combination Name
Tolcapone Oxaliplatin
Indication
Disease Entry Status REF
Neuroblastoma Phase 1 [1]
Component Drugs Tolcapone   DM8MNVO Oxaliplatin   DMQNWRD
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 Tolcapone
Disease Entry ICD 11 Status REF
Parkinson disease 8A00.0 Approved [2]
Tolcapone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Catechol-O-methyl-transferase (COMT) TTKWFB8 COMT_HUMAN Inhibitor [6]
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Tolcapone Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [7]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Decreases Expression [8]
Lipid transferase CIDEA (CIDEA) OTDUTSOV CIDEA_HUMAN Increases Expression [9]
Long-chain-fatty-acid--CoA ligase 1 (ACSL1) OTB06ESI ACSL1_HUMAN Decreases Expression [9]
Microsomal triglyceride transfer protein large subunit (MTTP) OTNUVSDT MTP_HUMAN Increases Expression [9]
Long-chain-fatty-acid--CoA ligase 5 (ACSL5) OT3L9XO3 ACSL5_HUMAN Decreases Expression [9]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Decreases Expression [10]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Decreases Expression [10]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [10]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [10]
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⏷ Show the Full List of 10 DOT(s)
Indication(s) of Oxaliplatin
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [3]
Appendiceal neoplasm N.A. Approved [3]
Cholangiocarcinoma 2C12.10 Approved [3]
Colon adenocarcinoma N.A. Approved [3]
Colorectal cancer 2B91.Z Approved [4]
Colorectal carcinoma N.A. Approved [3]
Endocrine gland neoplasm N.A. Approved [3]
Gallbladder carcinoma N.A. Approved [3]
Metastasis from malignant tumor of colon N.A. Approved [3]
Nasopharyngeal carcinoma 2B6B Approved [3]
Peritoneal neoplasm N.A. Approved [3]
Rectal adenocarcinoma 2B92 Approved [3]
Rectal neoplasm N.A. Approved [3]
Rectum mucinous adenocarcinoma N.A. Approved [3]
Colon cancer 2B90.Z Investigative [3]
Gastric cancer 2B72 Investigative [3]
Oxaliplatin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [11]
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Oxaliplatin Interacts with 5 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [12]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [13]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [14]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [15]
High affinity copper uptake protein 1 (SLC31A1) DTP8L4F COPT1_HUMAN Substrate [16]
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Oxaliplatin Interacts with 12 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [17]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [17]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [17]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [17]
Glutathione S-transferase pi (GSTP1) DEK6079 GSTP1_HUMAN Metabolism [18]
Glutathione S-transferase theta-1 (GSTT1) DE3PKUG GSTT1_HUMAN Metabolism [18]
Metallothionein-1A (MT1A) DE5ME8A MT1A_HUMAN Metabolism [18]
Metallothionein-2A (MT2A) DEFKGT7 MT2_HUMAN Metabolism [18]
Myeloperoxidase (MPO) DEA3U9Y PERM_HUMAN Metabolism [18]
Quinone reductase 1 (NQO1) DENP5RY NQO1_HUMAN Metabolism [18]
Superoxide dismutase 1 (SOD1) DEUTDON SODC_HUMAN Metabolism [18]
Glutathione S-transferase mu-1 (GSTM1) DEYZEJA GSTM1_HUMAN Metabolism [18]
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⏷ Show the Full List of 12 DME(s)
Oxaliplatin Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Protachykinin-1 (TAC1) OTM842YW TKN1_HUMAN Increases ADR [19]
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References

1 ClinicalTrials.gov (NCT02630043) Trial of Tolcapone With Oxaliplatin for Neuroblastoma
2 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: 6646).
3 Oxaliplatin 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: 7433).
5 Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism. Neurology. 2005 Dec 13;65(11):1820-2. doi: 10.1212/01.wnl.0000187066.81162.70.
6 Catechol-O-methyltransferase inhibitors in the management of Parkinson's disease. Semin Neurol. 2001;21(1):15-22.
7 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
8 The catechol-O-methyltransferase inhibitors tolcapone and entacapone uncouple and inhibit the mitochondrial respiratory chain in HepaRG cells. Toxicol In Vitro. 2017 Aug;42:337-347.
9 Effect of the Catechol-O-Methyltransferase Inhibitors Tolcapone and Entacapone on Fatty Acid Metabolism in HepaRG Cells. Toxicol Sci. 2018 Aug 1;164(2):477-488.
10 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
11 Structures of oxaliplatin-oligonucleotide adducts from DNA.J Mass Spectrom.2012 Oct;47(10):1282-93.
12 Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles. PLoS One. 2015 Jul 1;10(7):e0130727.
13 Effect of ABCG2 on cytotoxicity of platinum drugs: interference of EGFP. Toxicol In Vitro. 2008 Dec;22(8):1846-52.
14 Relevance of copper transporter 1 and organic cation transporters 1-3 for oxaliplatin uptake and drug resistance in colorectal cancer cells. Metallomics. 2018 Mar 1;10(3):414-425.
15 Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57.
16 Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs. Crit Rev Oncol Hematol. 2005 Jan;53(1):13-23.
17 The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
18 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
19 Polymorphic markers associated with severe oxaliplatin-induced, chronic peripheral neuropathy in colon cancer patients. Cancer. 2012 Jun 1;118(11):2828-36. doi: 10.1002/cncr.26614. Epub 2011 Oct 21.