Details of the Drug Combination

General Information of Drug Combination (ID: DC8J6PD)

Drug Combination Name
GSK461364 AT13387
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs GSK461364   DM0P729 AT13387   DM2B9E0
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: TC-71
Zero Interaction Potency (ZIP) Score: 16.012
Bliss Independence Score: 19.422
Loewe Additivity Score: 1.562
LHighest Single Agent (HSA) Score: 5.327

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of GSK461364
Disease Entry ICD 11 Status REF
Non-hodgkin lymphoma 2B33.5 Phase 1 [2]
Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
GSK461364 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Polo-like kinase 1 (PLK1) TTIYVQP PLK1_HUMAN Inhibitor [4]
------------------------------------------------------------------------------------
GSK461364 Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [5]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [5]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [5]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [5]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Phosphorylation [5]
------------------------------------------------------------------------------------
Indication(s) of AT13387
Disease Entry ICD 11 Status REF
Melanoma 2C30 Phase 1 [3]
AT13387 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Heat shock protein 90 alpha (HSP90A) TT78R5H HS90A_HUMAN Inhibitor [6]
------------------------------------------------------------------------------------
AT13387 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
mRNA-capping enzyme (RNGTT) OT59E0KX MCE1_HUMAN Decreases Expression [7]
------------------------------------------------------------------------------------

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: 5684).
3 Clinical pipeline report, company report or official report of Astex Pharmaceuticals.
4 Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist. 2009 Jun;14(6):559-70.
5 A specific inhibitor of polo-like kinase 1, GSK461364A, suppresses proliferation of Raji Burkitt's lymphoma cells through mediating cell cycle arrest, DNA damage, and apoptosis. Chem Biol Interact. 2020 Dec 1;332:109288. doi: 10.1016/j.cbi.2020.109288. Epub 2020 Oct 17.
6 Astex Presents Updates on AT13387, its HSP90 Inhibitor, and AT9283, its Multi-Targeted Kinase Inhibitor at the EORTC-NCI-AACR Cancer Conference. Astex. 2008.
7 RNA-binding proteins and heat-shock protein 90 are constituents of the cytoplasmic capping enzyme interactome. J Biol Chem. 2018 Oct 26;293(43):16596-16607. doi: 10.1074/jbc.RA118.004973. Epub 2018 Aug 30.