Details of the Drug Combination

General Information of Drug Combination (ID: DC1BFKW)

Drug Combination Name

Napabucasin Marizomib

Indication

Disease Entry	Status	REF
Diffuse intrinsic pontine glioma	Investigative	[1]

Component Drugs

Napabucasin DMDZ6Q3

Marizomib DME9QGW

N.A.

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: DIPG25

Zero Interaction Potency (ZIP) Score: 7.8

Bliss Independence Score: 7.35

Loewe Additivity Score: 4.34

LHighest Single Agent (HSA) Score: 7.74

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	[8]
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)	OT9RDS3H	IKKB_HUMAN	Decreases Expression	[8]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[9]
Krueppel-like factor 4 (KLF4)	OT4O9RQW	KLF4_HUMAN	Decreases Expression	[9]
Tyrosine-protein kinase JAK2 (JAK2)	OTBIDOOR	JAK2_HUMAN	Decreases Expression	[8]
Serine/threonine-protein kinase LATS1 (LATS1)	OTOOCG4R	LATS1_HUMAN	Decreases Expression	[8]
Aldehyde dehydrogenase 1A1 (ALDH1A1)	OTCUWZKB	AL1A1_HUMAN	Decreases Expression	[8]
Hypoxanthine-guanine phosphoribosyltransferase (HPRT1)	OTOEEEXG	HPRT_HUMAN	Decreases Expression	[8]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[8]
Pro-epidermal growth factor (EGF)	OTANRJ0L	EGF_HUMAN	Decreases Expression	[8]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[8]
Large ribosomal subunit protein uL10 (RPLP0)	OT3XKD6Y	RLA0_HUMAN	Decreases Expression	[8]
Integrin beta-1 (ITGB1)	OT6G1IAR	ITB1_HUMAN	Decreases Expression	[8]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[8]
Integrin alpha-4 (ITGA4)	OTSCAL0V	ITA4_HUMAN	Decreases Expression	[8]
Electron transfer flavoprotein subunit alpha, mitochondrial (ETFA)	OTXX61VZ	ETFA_HUMAN	Decreases Expression	[8]
Mucin-1 (MUC1)	OTHQI7IY	MUC1_HUMAN	Decreases Expression	[8]
CD44 antigen (CD44)	OT9TTJ41	CD44_HUMAN	Decreases Expression	[8]
Platelet endothelial cell adhesion molecule (PECAM1)	OTXOM4D9	PECA1_HUMAN	Decreases Expression	[8]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_HUMAN	Decreases Expression	[8]
Integrin alpha-2 (ITGA2)	OTPFL017	ITA2_HUMAN	Decreases Expression	[8]
Endoglin (ENG)	OTL2LSMI	EGLN_HUMAN	Decreases Expression	[8]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[8]
Kit ligand (KITLG)	OTB9AVQ4	SCF_HUMAN	Decreases Expression	[8]
Fibroblast growth factor receptor 2 (FGFR2)	OTLOPACK	FGFR2_HUMAN	Decreases Expression	[8]
Integrin alpha-6 (ITGA6)	OT3FA39C	ITA6_HUMAN	Decreases Expression	[8]
Signal transducer CD24 (CD24)	OT7CODJ4	CD24_HUMAN	Decreases Expression	[8]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Decreases Expression	[8]
Hematopoietic progenitor cell antigen CD34 (CD34)	OT1MOFLZ	CD34_HUMAN	Decreases Expression	[8]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Decreases Expression	[8]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[8]
Polycomb complex protein BMI-1 (BMI1)	OTROVLJ0	BMI1_HUMAN	Decreases Expression	[8]
TGF-beta receptor type-1 (TGFBR1)	OT40S1SJ	TGFR1_HUMAN	Decreases Expression	[8]
DNA-binding protein inhibitor ID-1 (ID1)	OTKGNZN5	ID1_HUMAN	Decreases Expression	[8]
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Decreases Expression	[8]
Transcription factor SOX-2 (SOX2)	OTFAWCAU	SOX2_HUMAN	Decreases Expression	[8]
Glycogen synthase kinase-3 beta (GSK3B)	OTL3L14B	GSK3B_HUMAN	Decreases Expression	[8]
Ataxin-1 (ATXN1)	OTQF0HNR	ATX1_HUMAN	Decreases Expression	[8]
Actin, cytoplasmic 1 (ACTB)	OT1MCP2F	ACTB_HUMAN	Decreases Expression	[8]
Beta-2-microglobulin (B2M)	OTDWN6NX	B2MG_HUMAN	Decreases Expression	[8]
Protein jagged-1 (JAG1)	OT3LGT6K	JAG1_HUMAN	Decreases Expression	[8]
POU domain, class 5, transcription factor 1 (POU5F1)	OTDHHN7O	PO5F1_HUMAN	Decreases Expression	[8]
Urokinase plasminogen activator surface receptor (PLAUR)	OTIRKKEQ	UPAR_HUMAN	Decreases Expression	[8]
Neurogenic locus notch homolog protein 2 (NOTCH2)	OTQ3Y9PA	NOTC2_HUMAN	Decreases Expression	[8]
Epithelial discoidin domain-containing receptor 1 (DDR1)	OTYW1SH8	DDR1_HUMAN	Decreases Expression	[8]
Tyrosine-protein kinase Mer (MERTK)	OTWBRAJ6	MERTK_HUMAN	Decreases Expression	[8]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Decreases Expression	[8]
Histone deacetylase 1 (HDAC1)	OTQDNOXZ	HDAC1_HUMAN	Decreases Expression	[8]
CD166 antigen (ALCAM)	OTCO4LP7	CD166_HUMAN	Decreases Expression	[8]
Flotillin-2 (FLOT2)	OTZ0QR5L	FLOT2_HUMAN	Decreases Expression	[8]
Tafazzin (TAFAZZIN)	OTDR57KI	TAZ_HUMAN	Decreases Expression	[8]
Krueppel-like factor 17 (KLF17)	OT5NWVP7	KLF17_HUMAN	Decreases Expression	[8]
Mastermind-like protein 1 (MAML1)	OTQA4DDN	MAML1_HUMAN	Decreases Expression	[8]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	OTAYZMOY	SIR1_HUMAN	Decreases Expression	[8]
Protein smoothened (SMO)	OTXXE208	SMO_HUMAN	Decreases Expression	[8]
Forkhead box protein P1 (FOXP1)	OTSG6XGF	FOXP1_HUMAN	Decreases Expression	[8]
Homeobox protein NANOG (NANOG)	OTUEY1FM	NANOG_HUMAN	Decreases Expression	[8]
Protein lin-28 homolog A (LIN28A)	OTJJBRCQ	LN28A_HUMAN	Decreases Expression	[8]
Dachshund homolog 1 (DACH1)	OTMKNAGG	DACH1_HUMAN	Decreases Expression	[8]
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⏷ Show the Full List of 59 DOT(s)

Indication(s) of Marizomib

Disease Entry	ICD 11	Status	REF
Glioblastoma of brain	2A00.00	Phase 3	[5]
Malignant glioma	2A00.0	Phase 1	[6]
Multiple myeloma	2A83	Phase 1	[6]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]

Marizomib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Proteasome (PS)	TTU7ZMG	NOUNIPROTAC	Inhibitor	[10]
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References

1	Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
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	ClinicalTrials.gov (NCT03345095) A Phase III Trial of With Marizomib in Patients With Newly Diagnosed Glioblastoma (MIRAGE). U.S. National Institutes of Health.
6	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
7	Clinical pipeline report, company report or official report of Triphase Accelerator .
8	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.
9	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.
10	Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets. 2011 Mar;11(3):254-84.