Details of the Drug Combination

General Information of Drug Combination (ID: DCP46OV)

Drug Combination Name
Trimetrexate Marizomib
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Trimetrexate   DMDEA85 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: 4.12
Bliss Independence Score: 4.39
Loewe Additivity Score: 2.82
LHighest Single Agent (HSA) Score: 6.34

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Trimetrexate
Disease Entry ICD 11 Status REF
Toxoplasmosis 1F57 Approved [2]
Trimetrexate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Polypeptide deformylase (PDF) TT9SL3Q DEFM_HUMAN Inhibitor [6]
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Trimetrexate Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [7]
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Trimetrexate Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Dihydrofolate reductase (DHFR) OT3DVIGM DYR_HUMAN Decreases Response To Substance [8]
GTPase KRas (KRAS) OT78QCN8 RASK_HUMAN Increases Response To Substance [9]
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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 [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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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 Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase. Antimicrob Agents Chemother. 2000 Nov;44(11):3092-6.
7 Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
8 Increased resistance to nitrogen mustards and antifolates following in vitro selection of murine fibroblasts and primary hematopoietic cells transduced with a bicistronic retroviral vector expressing the rat glutathione S-transferase A3 and a mutant dihydrofolate reductase. Cancer Gene Ther. 2003 Aug;10(8):637-46. doi: 10.1038/sj.cgt.7700619.
9 KRAS mutation status is associated with enhanced dependency on folate metabolism pathways in non-small cell lung cancer cells. Mol Cancer Ther. 2014 Jun;13(6):1611-24. doi: 10.1158/1535-7163.MCT-13-0649. Epub 2014 Mar 31.
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.