Details of the Drug Combination

General Information of Drug Combination (ID: DCUBM47)

Drug Combination Name
Napabucasin Regorafenib
Indication
Disease Entry Status REF
Advanced Gastrointestinal Cancer Phase 1 [1]
Component Drugs Napabucasin   DMDZ6Q3 Regorafenib   DMHSY1I
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

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 59 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]
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) OT9RDS3H IKKB_HUMAN Decreases Expression [7]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [8]
Krueppel-like factor 4 (KLF4) OT4O9RQW KLF4_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]
Aldehyde dehydrogenase 1A1 (ALDH1A1) OTCUWZKB AL1A1_HUMAN Decreases Expression [7]
Hypoxanthine-guanine phosphoribosyltransferase (HPRT1) OTOEEEXG HPRT_HUMAN Decreases Expression [7]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [7]
Pro-epidermal growth factor (EGF) OTANRJ0L EGF_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]
Integrin beta-1 (ITGB1) OT6G1IAR ITB1_HUMAN Decreases Expression [7]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [7]
Integrin alpha-4 (ITGA4) OTSCAL0V ITA4_HUMAN Decreases Expression [7]
Electron transfer flavoprotein subunit alpha, mitochondrial (ETFA) OTXX61VZ ETFA_HUMAN Decreases Expression [7]
Mucin-1 (MUC1) OTHQI7IY MUC1_HUMAN Decreases Expression [7]
CD44 antigen (CD44) OT9TTJ41 CD44_HUMAN Decreases Expression [7]
Platelet endothelial cell adhesion molecule (PECAM1) OTXOM4D9 PECA1_HUMAN Decreases Expression [7]
Epithelial cell adhesion molecule (EPCAM) OTHBZK5X EPCAM_HUMAN Decreases Expression [7]
Integrin alpha-2 (ITGA2) OTPFL017 ITA2_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]
Fibroblast growth factor receptor 2 (FGFR2) OTLOPACK FGFR2_HUMAN Decreases Expression [7]
Integrin alpha-6 (ITGA6) OT3FA39C ITA6_HUMAN Decreases Expression [7]
Signal transducer CD24 (CD24) OT7CODJ4 CD24_HUMAN Decreases Expression [7]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Decreases Expression [7]
Hematopoietic progenitor cell antigen CD34 (CD34) OT1MOFLZ CD34_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]
Polycomb complex protein BMI-1 (BMI1) OTROVLJ0 BMI1_HUMAN Decreases Expression [7]
TGF-beta receptor type-1 (TGFBR1) OT40S1SJ TGFR1_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]
Transcription factor SOX-2 (SOX2) OTFAWCAU SOX2_HUMAN Decreases Expression [7]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Decreases Expression [7]
Ataxin-1 (ATXN1) OTQF0HNR ATX1_HUMAN Decreases Expression [7]
Actin, cytoplasmic 1 (ACTB) OT1MCP2F ACTB_HUMAN Decreases Expression [7]
Beta-2-microglobulin (B2M) OTDWN6NX B2MG_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]
Urokinase plasminogen activator surface receptor (PLAUR) OTIRKKEQ UPAR_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]
Tyrosine-protein kinase Mer (MERTK) OTWBRAJ6 MERTK_HUMAN Decreases Expression [7]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Decreases Expression [7]
Histone deacetylase 1 (HDAC1) OTQDNOXZ HDAC1_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]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1) OTAYZMOY SIR1_HUMAN Decreases Expression [7]
Protein smoothened (SMO) OTXXE208 SMO_HUMAN Decreases Expression [7]
Forkhead box protein P1 (FOXP1) OTSG6XGF FOXP1_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 59 DOT(s)
Indication(s) of Regorafenib
Disease Entry ICD 11 Status REF
Gastrointestinal stromal tumour 2B5B Approved [5]
Metastasis from malignant tumor of colon N.A. Approved [5]
Metastatic colorectal cancer 2B91 Approved [6]
Regorafenib Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase Kit (KIT) TTX41N9 KIT_HUMAN Modulator [10]
Proto-oncogene c-Ret (RET) TT4DXQT RET_HUMAN Modulator [10]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Modulator [10]
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Regorafenib Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [11]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [12]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [13]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [11]
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Regorafenib Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [14]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [14]
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Regorafenib Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [9]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [9]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [15]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [9]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Activity [9]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [9]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [9]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Activity [9]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Expression [9]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [9]
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⏷ Show the Full List of 11 DOT(s)

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 Regorafenib 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: 5891).
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 Regorefenib induces extrinsic/intrinsic apoptosis and inhibits MAPK/NF-B-modulated tumor progression in bladder cancer in vitro and in vivo. Environ Toxicol. 2019 Jun;34(6):679-688. doi: 10.1002/tox.22734. Epub 2019 Feb 25.
10 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
11 Regorafenib is transported by the organic anion transporter 1B1 and the multidrug resistance protein 2. Biol Pharm Bull. 2015;38(4):582-6.
12 Brain and Testis Accumulation of Regorafenib is Restricted by Breast Cancer Resistance Protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1). Pharm Res. 2015 Jul;32(7):2205-16.
13 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
14 FDA Label of Regorafenib. The 2020 official website of the U.S. Food and Drug Administration.
15 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.