Details of the Drug Combination

General Information of Drug Combination (ID: DCCBSZN)

• Drug Combination Name: Fostamatinib + Marizomib
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  Fostamatinib (DM6AUHV): Small molecular drug
  Marizomib (DME9QGW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SU-DIPG-XIII
  Zero Interaction Potency (ZIP) Score: 2.209
  Bliss Independence Score: 7.305
  Loewe Additivity Score: 4.6
  LHighest Single Agent (HSA) Score: 0.389

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Fostamatinib

Disease Entry	ICD 11	Status	REF
Immune thrombocytopenic purpura	3B64.13	Approved	[2]
Rheumatoid arthritis	FA20	Phase 3	[3]

Fostamatinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tyrosine-protein kinase SYK (SYK)	TTOU65C	KSYK_HUMAN	Modulator	[7]

Fostamatinib Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
ATP-binding cassette sub-family B member 5 (ABCB5)	DTKVEXO	ABCB5_HUMAN	Substrate	[8]

Fostamatinib Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]

Indication(s) of Marizomib

Disease Entry	ICD 11	Status	REF
Glioblastoma of brain	2A00.00	Phase 3	[4]
Malignant glioma	2A00.0	Phase 1	[5]
Multiple myeloma	2A83	Phase 1	[5]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]

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] 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] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [3] 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: 7796).
• [4] ClinicalTrials.gov (NCT03345095) A Phase III Trial of With Marizomib in Patients With Newly Diagnosed Glioblastoma (MIRAGE). U.S. National Institutes of Health.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Clinical pipeline report, company report or official report of Triphase Accelerator .
• [7] 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. (Target id: 2230).
• [8] DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB12010)
• [9] Effects of CYP3A4 inhibitors ketoconazole and verapamil and the CYP3A4 inducer rifampicin on the pharmacokinetic parameters of fostamatinib: results from In vitro and phase I clinical studies. Drugs R D. 2016 Mar;16(1):81-92.
• [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.