Details of the Drug Combination

General Information of Drug Combination (ID: DCX2CN8)

Drug Combination Name
Napabucasin Oxaliplatin
Indication
Disease Entry Status REF
Advanced Gastrointestinal Cancer Phase 1 [1]
Component Drugs Napabucasin   DMDZ6Q3 Oxaliplatin   DMQNWRD
N.A. 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 Napabucasin
Disease Entry ICD 11 Status REF
Colorectal cancer 2B91.Z Phase 3 [2]
Pancreatic cancer 2C10 Phase 3 [2]
Solid tumour/cancer 2A00-2F9Z Phase 3 [3]
Advanced malignancy 2A00-2F9Z Phase 1/2 [2]
Gastrointestinal cancer 2C11 Phase 1/2 [2]
Hepatocellular carcinoma 2C12.02 Phase 1/2 [2]
Recurrent glioblastoma 2A00.00 Phase 1/2 [4]
Recurring respiratory infection CA07-CA45 Phase 1/2 [2]
Haematological malignancy 2B33.Y Phase 1 [2]
Napabucasin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Signal transducer and activator of transcription 3 (STAT3) TTH8FZW STAT3_HUMAN Inhibitor [2]
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Napabucasin Interacts with 35 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Decreases Expression [7]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [8]
Tyrosine-protein kinase JAK2 (JAK2) OTBIDOOR JAK2_HUMAN Decreases Expression [7]
Serine/threonine-protein kinase LATS1 (LATS1) OTOOCG4R LATS1_HUMAN Decreases Expression [7]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [7]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Decreases Expression [7]
Large ribosomal subunit protein uL10 (RPLP0) OT3XKD6Y RLA0_HUMAN Decreases Expression [7]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [7]
Electron transfer flavoprotein subunit alpha, mitochondrial (ETFA) OTXX61VZ ETFA_HUMAN Decreases Expression [7]
CD44 antigen (CD44) OT9TTJ41 CD44_HUMAN Decreases Expression [7]
Epithelial cell adhesion molecule (EPCAM) OTHBZK5X EPCAM_HUMAN Decreases Expression [7]
Endoglin (ENG) OTL2LSMI EGLN_HUMAN Decreases Expression [7]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Decreases Expression [7]
Kit ligand (KITLG) OTB9AVQ4 SCF_HUMAN Decreases Expression [7]
Signal transducer CD24 (CD24) OT7CODJ4 CD24_HUMAN Decreases Expression [7]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Expression [7]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [7]
DNA-binding protein inhibitor ID-1 (ID1) OTKGNZN5 ID1_HUMAN Decreases Expression [7]
Neurogenic locus notch homolog protein 1 (NOTCH1) OTI1WADQ NOTC1_HUMAN Decreases Expression [7]
Ataxin-1 (ATXN1) OTQF0HNR ATX1_HUMAN Decreases Expression [7]
Actin, cytoplasmic 1 (ACTB) OT1MCP2F ACTB_HUMAN Decreases Expression [7]
Protein jagged-1 (JAG1) OT3LGT6K JAG1_HUMAN Decreases Expression [7]
POU domain, class 5, transcription factor 1 (POU5F1) OTDHHN7O PO5F1_HUMAN Decreases Expression [7]
Neurogenic locus notch homolog protein 2 (NOTCH2) OTQ3Y9PA NOTC2_HUMAN Decreases Expression [7]
Epithelial discoidin domain-containing receptor 1 (DDR1) OTYW1SH8 DDR1_HUMAN Decreases Expression [7]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Decreases Expression [7]
CD166 antigen (ALCAM) OTCO4LP7 CD166_HUMAN Decreases Expression [7]
Flotillin-2 (FLOT2) OTZ0QR5L FLOT2_HUMAN Decreases Expression [7]
Tafazzin (TAFAZZIN) OTDR57KI TAZ_HUMAN Decreases Expression [7]
Krueppel-like factor 17 (KLF17) OT5NWVP7 KLF17_HUMAN Decreases Expression [7]
Mastermind-like protein 1 (MAML1) OTQA4DDN MAML1_HUMAN Decreases Expression [7]
Protein smoothened (SMO) OTXXE208 SMO_HUMAN Decreases Expression [7]
Homeobox protein NANOG (NANOG) OTUEY1FM NANOG_HUMAN Decreases Expression [7]
Protein lin-28 homolog A (LIN28A) OTJJBRCQ LN28A_HUMAN Decreases Expression [7]
Dachshund homolog 1 (DACH1) OTMKNAGG DACH1_HUMAN Decreases Expression [7]
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⏷ Show the Full List of 35 DOT(s)
Indication(s) of Oxaliplatin
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [5]
Appendiceal neoplasm N.A. Approved [5]
Cholangiocarcinoma 2C12.10 Approved [5]
Colon adenocarcinoma N.A. Approved [5]
Colorectal cancer 2B91.Z Approved [6]
Colorectal carcinoma N.A. Approved [5]
Endocrine gland neoplasm N.A. Approved [5]
Gallbladder carcinoma N.A. Approved [5]
Metastasis from malignant tumor of colon N.A. Approved [5]
Nasopharyngeal carcinoma 2B6B Approved [5]
Peritoneal neoplasm N.A. Approved [5]
Rectal adenocarcinoma 2B92 Approved [5]
Rectal neoplasm N.A. Approved [5]
Rectum mucinous adenocarcinoma N.A. Approved [5]
Colon cancer 2B90.Z Investigative [5]
Gastric cancer 2B72 Investigative [5]
Oxaliplatin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [9]
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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 [10]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [11]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [12]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [13]
High affinity copper uptake protein 1 (SLC31A1) DTP8L4F COPT1_HUMAN Substrate [14]
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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 [15]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [15]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [15]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [15]
Glutathione S-transferase pi (GSTP1) DEK6079 GSTP1_HUMAN Metabolism [16]
Glutathione S-transferase theta-1 (GSTT1) DE3PKUG GSTT1_HUMAN Metabolism [16]
Metallothionein-1A (MT1A) DE5ME8A MT1A_HUMAN Metabolism [16]
Metallothionein-2A (MT2A) DEFKGT7 MT2_HUMAN Metabolism [16]
Myeloperoxidase (MPO) DEA3U9Y PERM_HUMAN Metabolism [16]
Quinone reductase 1 (NQO1) DENP5RY NQO1_HUMAN Metabolism [16]
Superoxide dismutase 1 (SOD1) DEUTDON SODC_HUMAN Metabolism [16]
Glutathione S-transferase mu-1 (GSTM1) DEYZEJA GSTM1_HUMAN Metabolism [16]
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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 [17]
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References

1 ClinicalTrials.gov (NCT02024607) A Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Advanced Gastrointestinal Cancer
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 First-in-Class Cancer Stemness Inhibitor Shows Promising Results in Advanced Colorectal Cancer. 2016 ASCO GI Conference. January 26, 2016.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Oxaliplatin FDA Label
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. (Ligand id: 7433).
7 Suppression of cancer relapse and metastasis by inhibiting cancer stemness. Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1839-44. doi: 10.1073/pnas.1424171112. Epub 2015 Jan 20.
8 Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin. Cancer Med. 2016 Jun;5(6):1251-8. doi: 10.1002/cam4.675. Epub 2016 Feb 21.
9 Structures of oxaliplatin-oligonucleotide adducts from DNA.J Mass Spectrom.2012 Oct;47(10):1282-93.
10 Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles. PLoS One. 2015 Jul 1;10(7):e0130727.
11 Effect of ABCG2 on cytotoxicity of platinum drugs: interference of EGFP. Toxicol In Vitro. 2008 Dec;22(8):1846-52.
12 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.
13 Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57.
14 Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs. Crit Rev Oncol Hematol. 2005 Jan;53(1):13-23.
15 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.
16 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
17 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.