Details of the Drug Combination

General Information of Drug Combination (ID: DCAWL16)

Drug Combination Name
PF-3758309 Marizomib
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs PF-3758309   DM36PKZ 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: 6.9
Bliss Independence Score: 7.03
Loewe Additivity Score: 8.87
LHighest Single Agent (HSA) Score: 11.4

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PF-3758309
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
PF-3758309 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PAK-4 protein kinase (PAK4) TT7Y3BZ PAK4_HUMAN Inhibitor [2]
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PF-3758309 Interacts with 48 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase PAK 4 (PAK4) OTY8JEE4 PAK4_HUMAN Increases Response To Substance [6]
Suppressor of cytokine signaling 3 (SOCS3) OTY183WJ SOCS3_HUMAN Decreases Expression [6]
T-box transcription factor TBX3 (TBX3) OTM64N7K TBX3_HUMAN Increases Expression [6]
Receptor-interacting serine/threonine-protein kinase 2 (RIPK2) OT0KMIYQ RIPK2_HUMAN Decreases Expression [6]
Tumor necrosis factor ligand superfamily member 14 (TNFSF14) OT5QRF09 TNF14_HUMAN Increases Expression [6]
Nucleolar protein 3 (NOL3) OT1K0L0D NOL3_HUMAN Increases Expression [6]
STAM-binding protein (STAMBP) OTOT2OXM STABP_HUMAN Decreases Expression [6]
Interferon alpha-2 (IFNA2) OT4GII73 IFNA2_HUMAN Increases Expression [6]
Interferon beta (IFNB1) OTYQGUB5 IFNB_HUMAN Increases Expression [6]
Alpha-crystallin B chain (CRYAB) OTY4JGYU CRYAB_HUMAN Increases Expression [6]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [6]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [6]
CCAAT/enhancer-binding protein beta (CEBPB) OTM9MQIA CEBPB_HUMAN Decreases Expression [6]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Decreases Expression [6]
Azurocidin (AZU1) OTHXU264 CAP7_HUMAN Decreases Expression [6]
Brain-derived neurotrophic factor (BDNF) OTLGH7EW BDNF_HUMAN Increases Expression [6]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [6]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [6]
Caspase-1 (CASP1) OTZ3YQFU CASP1_HUMAN Decreases Expression [6]
CD70 antigen (CD70) OTHB2AL1 CD70_HUMAN Increases Expression [6]
Tumor necrosis factor ligand superfamily member 8 (TNFSF8) OTDYGDJ3 TNFL8_HUMAN Decreases Expression [6]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [6]
B-cell lymphoma 6 protein (BCL6) OTQAWWO1 BCL6_HUMAN Increases Expression [6]
Caspase-6 (CASP6) OTXLD3EC CASP6_HUMAN Decreases Expression [6]
Protein kinase C zeta type (PRKCZ) OTN2FE42 KPCZ_HUMAN Increases Expression [6]
Elongation factor 1-alpha 2 (EEF1A2) OT9Z23K5 EF1A2_HUMAN Increases Expression [6]
Lymphotoxin-beta (LTB) OTUFS8CF TNFC_HUMAN Increases Expression [6]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Decreases Expression [6]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [6]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Expression [6]
C-Jun-amino-terminal kinase-interacting protein 2 (MAPK8IP2) OTDUHLN0 JIP2_HUMAN Increases Expression [6]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [6]
Tumor necrosis factor receptor type 1-associated DEATH domain protein (TRADD) OTBOSJHO TRADD_HUMAN Increases Expression [6]
Bcl-2-related protein A1 (BCL2A1) OTWRYSNA B2LA1_HUMAN Decreases Expression [6]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Increases Expression [6]
Gamma-interferon-inducible protein 16 (IFI16) OT4SPU0U IF16_HUMAN Decreases Expression [6]
Quinone oxidoreductase PIG3 (TP53I3) OTSCM68G QORX_HUMAN Increases Expression [6]
Ectodysplasin-A (EDA) OTAKS5WS EDA_HUMAN Increases Expression [6]
Bcl-2-like protein 2 (BCL2L2) OTMKVO0J B2CL2_HUMAN Increases Expression [6]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [6]
Homeobox protein Nkx-3.1 (NKX3-1) OT0DO6ZU NKX31_HUMAN Increases Expression [6]
Caspase recruitment domain-containing protein 6 (CARD6) OTEI1PJ1 CARD6_HUMAN Decreases Expression [6]
Protein AATF (AATF) OT1QOKLD AATF_HUMAN Decreases Expression [6]
Bcl-2-associated transcription factor 1 (BCLAF1) OT7T8H6A BCLF1_HUMAN Decreases Expression [6]
Serine/threonine-protein kinase pim-2 (PIM2) OTHQGU3I PIM2_HUMAN Decreases Expression [6]
Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D) OTOSRDJT TR10D_HUMAN Decreases Expression [6]
Tumor necrosis factor ligand superfamily member 18 (TNFSF18) OT3ANRX1 TNF18_HUMAN Decreases Expression [6]
TNF receptor-associated factor 6 (TRAF6) OTA5GO5K TRAF6_HUMAN Increases Expression [6]
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⏷ Show the Full List of 48 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 [7]
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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 Small-molecule p21-activated kinase inhibitor PF-3758309 is a potent inhibitor of oncogenic signaling and tumor growth. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9446-51.
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 Inhibition of neuroblastoma proliferation by PF-3758309, a small-molecule inhibitor that targets p21-activated kinase 4. Oncol Rep. 2017 Nov;38(5):2705-2716. doi: 10.3892/or.2017.5989. Epub 2017 Sep 22.
7 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.