Details of the Drug Combination

General Information of Drug Combination (ID: DC8BGNB)

Drug Combination Name
MK-4827 Marizomib
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs MK-4827   DMLYGH4 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: 1.04
Bliss Independence Score: 1.06
Loewe Additivity Score: 2.89
LHighest Single Agent (HSA) Score: 4.08

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MK-4827
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 3 [2]
Breast cancer 2C60-2C65 Phase 2 [3]
Ewing sarcoma 2B52 Phase 1 [3]
MK-4827 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Poly [ADP-ribose] polymerase (PARP) TTEBCY8 NOUNIPROTAC Modulator [7]
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MK-4827 Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [8]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Metabolism [9]
Beta-glucuronidase (GUSB) DEP54UE BGLR_HUMAN Metabolism [9]
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MK-4827 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [10]
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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 [11]
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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 ClinicalTrials.gov (NCT03602859) A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST). U.S. National Institutes of Health.
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
8 Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009 Nov 26;52(22):7170-85.
9 Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
10 Autophagy up-regulated by MEK/ERK promotes the repair of DNA damage caused by aflatoxin B1. Toxicol Mech Methods. 2022 Feb;32(2):87-96. doi: 10.1080/15376516.2021.1968985. Epub 2021 Aug 26.
11 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.