Details of the Drug Combination

General Information of Drug Combination (ID: DCWYKA5)

Drug Combination Name
PI-103 Marizomib
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs PI-103   DMEK4TJ 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: 3.5
Bliss Independence Score: 3.05
Loewe Additivity Score: 2.91
LHighest Single Agent (HSA) Score: 9.02

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PI-103
Disease Entry ICD 11 Status REF
Haematological malignancy 2B33.Y Investigative [2]
PI-103 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Inhibitor [6]
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PI-103 Interacts with 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Expression [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Expression [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [9]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [9]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [10]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Expression [7]
Dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2) OTUE7Z91 MP2K2_HUMAN Increases Phosphorylation [9]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) OT4Y9NQI MP2K1_HUMAN Increases Phosphorylation [9]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Increases Expression [8]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Increases Expression [8]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Phosphorylation [11]
Carbonic anhydrase 9 (CA9) OTNA51XT CAH9_HUMAN Decreases Phosphorylation [11]
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⏷ Show the Full List of 12 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 [12]
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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 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: 5701).
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 The PI3K/Akt pathway as a target in the treatment of hematologic malignancies. Anticancer Agents Med Chem. 2009 Jun;9(5):550-9.
7 PI3K inhibition enhances doxorubicin-induced apoptosis in sarcoma cells. PLoS One. 2012;7(12):e52898. doi: 10.1371/journal.pone.0052898. Epub 2012 Dec 31.
8 The dual PI3K/mTOR inhibitor PI-103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells. Int J Cancer. 2010 Apr 1;126(7):1549-61. doi: 10.1002/ijc.24926.
9 PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. Anticancer Res. 2010 Dec;30(12):4951-8.
10 Inhibition of class I phosphoinositide 3-kinase activity impairs proliferation and triggers apoptosis in acute promyelocytic leukemia without affecting atra-induced differentiation. Cancer Res. 2009 Feb 1;69(3):1027-36. doi: 10.1158/0008-5472.CAN-08-2608. Epub 2009 Jan 27.
11 GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1 (HIF-1) pathways. J Clin Endocrinol Metab. 2011 Dec;96(12):E1934-43. doi: 10.1210/jc.2011-1426. Epub 2011 Oct 12.
12 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.