Details of the Drug Combination

General Information of Drug Combination (ID: DCMMTIG)

Drug Combination Name
PD-0173955 GSK2126458
Indication
Disease Entry Status REF
Hepatoblastoma Investigative [1]
Component Drugs PD-0173955   DMOZEW9 GSK2126458   DMM7ZXR
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HB3
Zero Interaction Potency (ZIP) Score: 7.743
Bliss Independence Score: 12.661
Loewe Additivity Score: 4.398
LHighest Single Agent (HSA) Score: 3.955

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PD-0173955
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
PD-0173955 Interacts with 6 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
LCK tyrosine protein kinase (LCK) TT860QF LCK_HUMAN Inhibitor [4]
Fusion protein Bcr-Abl (Bcr-Abl) TTS7G69 BCR_HUMAN-ABL1_HUMAN Inhibitor [5]
Fibroblast growth factor receptor 1 (FGFR1) TTRLW2X FGFR1_HUMAN Inhibitor [4]
Platelet-derived growth factor receptor alpha (PDGFRA) TT8FYO9 PGFRA_HUMAN Inhibitor [4]
Platelet-derived growth factor receptor beta (PDGFRB) TTI7421 PGFRB_HUMAN Inhibitor [4]
Proto-oncogene c-Src (SRC) TT6PKBN SRC_HUMAN Inhibitor [4]
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⏷ Show the Full List of 6 DTT(s)
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 [6]
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GSK2126458 Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Decreases Phosphorylation [7]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [7]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [8]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [8]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [7]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [8]
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⏷ Show the Full List of 7 DOT(s)

References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
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: 5699).
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 Biochemical and cellular effects of c-Src kinase-selective pyrido[2, 3-d]pyrimidine tyrosine kinase inhibitors. Biochem Pharmacol. 2000 Oct 1;60(7):885-98.
5 Structural insights into the ATP binding pocket of the anaplastic lymphoma kinase by site-directed mutagenesis, inhibitor binding analysis, and hom... J Med Chem. 2006 Sep 21;49(19):5759-68.
6 Company report (GSK)
7 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.
8 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.