Details of the Drug Combination

General Information of Drug Combination (ID: DCUWCSH)

Drug Combination Name
AZD8055 PHA-739358
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs AZD8055   DM7L8SG PHA-739358   DMGYBZI
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: 3.235
Bliss Independence Score: 1.393
Loewe Additivity Score: 1.091
LHighest Single Agent (HSA) Score: 3.889

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of AZD8055
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 1/2 [2]
AZD8055 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [4]
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AZD8055 Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [5]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [5]
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Indication(s) of PHA-739358
Disease Entry ICD 11 Status REF
Prostate cancer 2C82.0 Phase 2 [3]
PHA-739358 Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aurora kinase B (AURKB) TT5LS6T AURKB_HUMAN Inhibitor [6]
Aurora B messenger RNA (AURKB mRNA) TT9RTBL AURKB_HUMAN Inhibitor [7]
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [6]
Aurora kinase C (AURKC) TTLYXIT AURKC_HUMAN Inhibitor [7]
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PHA-739358 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Response To Substance [8]
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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: 7714).
3 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: 7937).
4 Clinical pipeline report, company report or official report of AstraZeneca (2009).
5 Frenolicin B Targets Peroxiredoxin 1 and Glutaredoxin 3 to Trigger ROS/4E-BP1-Mediated Antitumor Effects. Cell Chem Biol. 2019 Mar 21;26(3):366-377.e12. doi: 10.1016/j.chembiol.2018.11.013. Epub 2019 Jan 17.
6 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
7 Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 2005 Apr 21;48(8):3080-4.
8 Abcg2 overexpression represents a novel mechanism for acquired resistance to the multi-kinase inhibitor Danusertib in BCR-ABL-positive cells in vitro. PLoS One. 2011 Apr 26;6(4):e19164. doi: 10.1371/journal.pone.0019164.