Details of the Drug Combination

General Information of Drug Combination (ID: DC9QHDA)

Drug Combination Name
TAK-733 GSK2126458
Indication
Disease Entry Status REF
Glioblastoma Investigative [1]
Component Drugs TAK-733   DMC4RNA GSK2126458   DMM7ZXR
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: JHH-136
Zero Interaction Potency (ZIP) Score: 41.938
Bliss Independence Score: 41.646
Loewe Additivity Score: 17.366
LHighest Single Agent (HSA) Score: 23.407

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of TAK-733
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
TAK-733 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MAPK/ERK kinase kinase (MAP3K) TTROQ37 NOUNIPROTAC Modulator [4]
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Indication(s) of GSK2126458
Disease Entry ICD 11 Status REF
Lymphoma 2A80-2A86 Phase 1 [3]
GSK2126458 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Modulator [5]
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GSK2126458 Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Decreases Phosphorylation [6]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [7]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [7]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [6]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 ClinicalTrials.gov (NCT00948467) Study of TAK-733 in Adult Patients With Advanced Nonhematologic Malignancies. U.S. National Institutes of Health.
3 Dual PI3K/mTOR inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma. Mol Cancer Ther. 2015 Feb;14(2):429-39.
4 MEK and the inhibitors: from bench to bedside. J Hematol Oncol. 2013; 6: 27.
5 Company report (GSK)
6 Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells. Cancer Biol Ther. 2011 Jun 1;11(11):938-46. doi: 10.4161/cbt.11.11.15527. Epub 2011 Jun 1.
7 Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.