Details of the Drug Combination

General Information of Drug Combination (ID: DCSV088)

Drug Combination Name
Napabucasin Capecitabine
Indication
Disease Entry Status REF
Colorectal Cancer Phase 1 [1]
Component Drugs Napabucasin   DMDZ6Q3 Capecitabine   DMTS85L
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 Capecitabine
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [5]
Colon adenocarcinoma N.A. Approved [5]
Colorectal cancer 2B91.Z Approved [6]
Metastasis from malignant tumor of colon N.A. Approved [5]
Rectal adenocarcinoma 2B92 Approved [5]
Breast cancer 2C60-2C65 Phase 3 [6]
Colon cancer 2B90.Z Investigative [5]
Gastric cancer 2B72 Investigative [5]
Capecitabine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Candida Thymidylate synthase (Candi TMP1) TTU6BFZ TYSY_CANAL Inhibitor [11]
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Capecitabine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytidine aminohydrolase (CDA) DEKEDRC CDD_HUMAN Metabolism [12]
Thymidine phosphorylase (TYMP) DE4HCYL TYPH_HUMAN Metabolism [13]
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Capecitabine Interacts with 65 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Dihydropyrimidine dehydrogenase (DPYD) OTWRF2NR DPYD_HUMAN Increases Expression [14]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [15]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Expression [15]
C-C motif chemokine 21 (CCL21) OT7DOXEM CCL21_HUMAN Decreases Expression [9]
CCN family member 1 (CCN1) OTKJBEMD CCN1_HUMAN Decreases Expression [9]
Aquaporin-8 (AQP8) OT99JKME AQP8_HUMAN Increases Expression [9]
Complement C3 (C3) OTCH5GS0 CO3_HUMAN Decreases Expression [9]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1) OTC6GISG DQA1_HUMAN Decreases Expression [9]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Secretion [16]
B-lymphocyte antigen CD20 (MS4A1) OTZTVUBX CD20_HUMAN Decreases Expression [9]
Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1) OTGP6GA4 NR4A1_HUMAN Decreases Expression [9]
40-kDa huntingtin-associated protein (F8A1) OTXTQ59R HAP40_HUMAN Decreases Expression [9]
Chloride anion exchanger (SLC26A3) OTBNK2U2 S26A3_HUMAN Increases Expression [9]
Nuclear receptor subfamily 4 group A member 2 (NR4A2) OT3F9IR2 NR4A2_HUMAN Decreases Expression [9]
Potassium-transporting ATPase alpha chain 2 (ATP12A) OTSQSKEK AT12A_HUMAN Increases Expression [9]
Serine/threonine-protein kinase SIK1 (SIK1) OT6FCHME SIK1_HUMAN Decreases Expression [9]
Hemoglobin subunit beta (HBB) OT514IKQ HBB_HUMAN Decreases Expression [9]
Hemoglobin subunit alpha (HBA1) OTW2BQF4 HBA_HUMAN Decreases Expression [9]
Paired box protein Pax-5 (PAX5) OTYBJJWX PAX5_HUMAN Decreases Expression [9]
Endoplasmic reticulum aminopeptidase 2 (ERAP2) OTEMENYF ERAP2_HUMAN Decreases Expression [9]
Fc receptor-like A (FCRLA) OT6MK4M1 FCRLA_HUMAN Decreases Expression [9]
Leucine-rich repeat-containing protein 15 (LRRC15) OTX7JL8H LRC15_HUMAN Decreases Expression [9]
C-C motif chemokine 19 (CCL19) OTQ2UJMH CCL19_HUMAN Decreases Expression [9]
E3 ubiquitin-protein ligase TRIM31 (TRIM31) OT7VW6RP TRI31_HUMAN Increases Expression [9]
Interleukin-1 receptor type 2 (IL1R2) OT0G7E35 IL1R2_HUMAN Increases Response To Substance [10]
Interleukin-17 receptor B (IL17RB) OT0KDNSF I17RB_HUMAN Increases Response To Substance [10]
Glycogen phosphorylase, brain form (PYGB) OT2ZTJT0 PYGB_HUMAN Increases Response To Substance [10]
Calcium and integrin-binding protein 1 (CIB1) OT4BVCRU CIB1_HUMAN Increases Response To Substance [10]
1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2) OT5I4Y9K PLCB_HUMAN Increases Response To Substance [10]
cAMP-dependent protein kinase catalytic subunit beta (PRKACB) OT6RMDCE KAPCB_HUMAN Decreases Response To Substance [10]
Claudin-3 (CLDN3) OT71MN9S CLD3_HUMAN Increases Response To Substance [10]
Replication protein A 70 kDa DNA-binding subunit (RPA1) OT76POLP RFA1_HUMAN Decreases Response To Substance [10]
Protein flightless-1 homolog (FLII) OT7G9JG6 FLII_HUMAN Decreases Response To Substance [10]
Stress-induced-phosphoprotein 1 (STIP1) OT7TXLOX STIP1_HUMAN Decreases Response To Substance [10]
Ras-related protein R-Ras2 (RRAS2) OT83NCEB RRAS2_HUMAN Decreases Response To Substance [10]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Response To Substance [10]
Cocaine esterase (CES2) OTC647SQ EST2_HUMAN Increases Response To Substance [17]
Ras-related protein Rab-40B (RAB40B) OTCA9ZF5 RB40B_HUMAN Increases Response To Substance [10]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Increases Response To Substance [10]
Iron-sulfur clusters transporter ABCB7, mitochondrial (ABCB7) OTDNTHNR ABCB7_HUMAN Decreases Response To Substance [10]
Tyrosine-protein phosphatase non-receptor type 13 (PTPN13) OTESFZSO PTN13_HUMAN Decreases Response To Substance [10]
ADP-ribosylation factor-like protein 4D (ARL4D) OTG5I3KU ARL4D_HUMAN Decreases Response To Substance [10]
Double-strand break repair protein MRE11 (MRE11) OTGU8TZM MRE11_HUMAN Decreases Response To Substance [10]
Inorganic pyrophosphatase (PPA1) OTHZK1QB IPYR_HUMAN Increases Response To Substance [10]
Polycystin-2 (PKD2) OTIXBU8H PKD2_HUMAN Decreases Response To Substance [10]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Response To Substance [10]
Transcriptional activator Myb (MYB) OTJH64IV MYB_HUMAN Increases Response To Substance [10]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (PLCE1) OTJISZOX PLCE1_HUMAN Increases Response To Substance [10]
Plakophilin-2 (PKP2) OTJOVF68 PKP2_HUMAN Increases Response To Substance [10]
Transcriptional enhancer factor TEF-1 (TEAD1) OTK6971C TEAD1_HUMAN Decreases Response To Substance [10]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Response To Substance [10]
Myelin regulatory factor (MYRF) OTKF6AEB MYRF_HUMAN Increases Response To Substance [10]
Galectin-4 (LGALS4) OTKQCG0H LEG4_HUMAN Increases Response To Substance [10]
Four and a half LIM domains protein 1 (FHL1) OTN535SU FHL1_HUMAN Decreases Response To Substance [10]
Hepatoma-derived growth factor-related protein 3 (HDGFL3) OTNN7WYH HDGR3_HUMAN Decreases Response To Substance [10]
E3 ubiquitin-protein ligase TRIM15 (TRIM15) OTNYAKP6 TRI15_HUMAN Increases Response To Substance [10]
Dermatan-sulfate epimerase (DSE) OTQ108VJ DSE_HUMAN Decreases Response To Substance [10]
Anterior gradient protein 2 homolog (AGR2) OTRRZT7W AGR2_HUMAN Increases Response To Substance [10]
Receptor tyrosine-protein kinase erbB-3 (ERBB3) OTRSST0A ERBB3_HUMAN Increases Response To Substance [10]
Aldo-keto reductase family 1 member B1 (AKR1B1) OTRX72TH ALDR_HUMAN Decreases Response To Substance [10]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Increases Response To Substance [10]
3-ketoacyl-CoA thiolase, peroxisomal (ACAA1) OTVKRET0 THIK_HUMAN Increases Response To Substance [10]
Tissue alpha-L-fucosidase (FUCA1) OTW71IK4 FUCO_HUMAN Increases Response To Substance [10]
GTPase HRas (HRAS) OTWQN0DP RASH_HUMAN Decreases Response To Substance [10]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Increases Response To Substance [10]
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⏷ Show the Full List of 65 DOT(s)

References

1 ClinicalTrials.gov (NCT01776307) A Study of BBI608 in Adult Patients With Advanced Colorectal 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 Capecitabine 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: 6799).
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 Gene expression responses reflecting 5-FU-induced toxicity: Comparison between patient colon tissue and 3D human colon organoids. Toxicol Lett. 2022 Dec 1;371:17-24. doi: 10.1016/j.toxlet.2022.09.013. Epub 2022 Sep 29.
10 Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.
11 UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res. 2005 Feb 1;11(3):1226-36.
12 Augmentation of the antitumor activity of capecitabine by a tumor selective dihydropyrimidine dehydrogenase inhibitor, RO0094889. Int J Cancer. 2003 Sep 20;106(5):799-805.
13 Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther. 2002 Oct;1(12):1139-45.
14 DPD is a molecular determinant of capecitabine efficacy in colorectal cancer. Int J Oncol. 2007 Aug;31(2):413-8.
15 Effects of capecitabine and vinorelbine on cell proliferation, metabolism and COX2 and p16 expression in breast cancer cell lines and solid tumour tissues. Biomed Pharmacother. 2007 Oct;61(9):596-600.
16 P38 MAPK, NF-B, and JAK-STAT3 Signaling Pathways Involved in Capecitabine-Induced Hand-Foot Syndrome via Interleukin 6 or Interleukin 8 Abnormal Expression. Chem Res Toxicol. 2022 Mar 21;35(3):422-430. doi: 10.1021/acs.chemrestox.1c00317. Epub 2022 Feb 11.
17 A carboxylesterase 2 gene polymorphism as predictor of capecitabine on response and time to progression. Curr Drug Metab. 2008 May;9(4):336-43. doi: 10.2174/138920008784220646.