Details of the Drug Combination

General Information of Drug Combination (ID: DC1BFKW)

• Drug Combination Name: Napabucasin + Marizomib
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  Napabucasin (DMDZ6Q3): N.A.
  Marizomib (DME9QGW): Small molecular drug
• 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

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]

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	[8]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_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]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_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]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[8]
Electron transfer flavoprotein subunit alpha, mitochondrial (ETFA)	OTXX61VZ	ETFA_HUMAN	Decreases Expression	[8]
CD44 antigen (CD44)	OT9TTJ41	CD44_HUMAN	Decreases Expression	[8]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_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]
Signal transducer CD24 (CD24)	OT7CODJ4	CD24_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]
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]
Ataxin-1 (ATXN1)	OTQF0HNR	ATX1_HUMAN	Decreases Expression	[8]
Actin, cytoplasmic 1 (ACTB)	OT1MCP2F	ACTB_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]
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]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_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]
Protein smoothened (SMO)	OTXXE208	SMO_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]

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]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [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.