General Information of Drug Combination (ID: DCV1CNF)

Drug Combination Name
MCI-186 Marizomib
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs MCI-186   DM8ZHP1 Marizomib   DME9QGW
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DIPG25
Zero Interaction Potency (ZIP) Score: 4.78
Bliss Independence Score: 5.2
Loewe Additivity Score: 3.71
LHighest Single Agent (HSA) Score: 4.41

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MCI-186
Disease Entry ICD 11 Status REF
Amyotrophic lateral sclerosis 8B60.0 Approved [2]
MCI-186 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Apoptosis regulator Bcl-2 (BCL-2) TTJGNVC BCL2_HUMAN Regulator (upregulator) [6]
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MCI-186 Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [7]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [7]
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MCI-186 Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [8]
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MCI-186 Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Beta-nerve growth factor (NGF) OTOLABJT NGF_HUMAN Increases Expression [9]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Decreases Activity [10]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [11]
Nitric oxide synthase 3 (NOS3) OTLDT7NR NOS3_HUMAN Decreases Degradation [12]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [11]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Increases Phosphorylation [9]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [11]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [11]
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⏷ Show the Full List of 8 DOT(s)
Indication(s) of Marizomib
Disease Entry ICD 11 Status REF
Glioblastoma of brain 2A00.00 Phase 3 [3]
Malignant glioma 2A00.0 Phase 1 [4]
Multiple myeloma 2A83 Phase 1 [4]
Solid tumour/cancer 2A00-2F9Z Phase 1 [5]
Marizomib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Proteasome (PS) TTU7ZMG NOUNIPROTAC Inhibitor [13]
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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 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
3 ClinicalTrials.gov (NCT03345095) A Phase III Trial of With Marizomib in Patients With Newly Diagnosed Glioblastoma (MIRAGE). U.S. National Institutes of Health.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Clinical pipeline report, company report or official report of Triphase Accelerator .
6 Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
7 Human organic anion transporters 1 (hOAT1/SLC22A6) and 3 (hOAT3/SLC22A8) transport edaravone (MCI-186; 3-methyl-1-phenyl-2-pyrazolin-5-one) and its sulfate conjugate. Drug Metab Dispos. 2007 Aug;35(8):1429-34.
8 A novel administration route for edaravone: I. Effects of metabolic inhibitors on skin permeability of edaravone. Int J Pharm. 2009 May 8;372(1-2):33-8.
9 Edaravone improves the expression of nerve growth factor in human astrocytes subjected to hypoxia/reoxygenation. Neurosci Res. 2010 Mar;66(3):284-9. doi: 10.1016/j.neures.2009.11.011. Epub 2009 Nov 30.
10 Edaravone inhibits rheumatoid synovial cell proliferation and migration. Free Radic Res. 2006 Feb;40(2):121-5. doi: 10.1080/10715760500401116.
11 A novel pyrazolone-based derivative induces apoptosis in human esophageal cells via reactive oxygen species (ROS) generation and caspase-dependent mitochondria-mediated pathway. Chem Biol Interact. 2015 Apr 25;231:1-9. doi: 10.1016/j.cbi.2015.02.004. Epub 2015 Feb 13.
12 Edaravone, a novel radical scavenger, inhibits oxidative modification of low-density lipoprotein (LDL) and reverses oxidized LDL-mediated reduction in the expression of endothelial nitric oxide synthase. Atherosclerosis. 2005 Mar;179(1):97-102. doi: 10.1016/j.atherosclerosis.2004.10.037. Epub 2004 Dec 19.
13 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.