Details of the Drug Combination

General Information of Drug Combination (ID: DCES5N8)

Drug Combination Name
(-)-englerin A PHA-739358
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs (-)-englerin A   DMPQBWY PHA-739358   DMGYBZI
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: TC-71
Zero Interaction Potency (ZIP) Score: 23.326
Bliss Independence Score: 22.686
Loewe Additivity Score: 8.945
LHighest Single Agent (HSA) Score: 11.102

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of (-)-englerin A
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
(-)-englerin A Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Short transient receptor potential channel 5 (TRPC5) TT32NQ1 TRPC5_HUMAN Agonist [4]
Short transient receptor potential channel 4 (TRPC4) TTX0H5W TRPC4_HUMAN Agonist [4]
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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 [5]
Aurora B messenger RNA (AURKB mRNA) TT9RTBL AURKB_HUMAN Inhibitor [6]
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [5]
Aurora kinase C (AURKC) TTLYXIT AURKC_HUMAN Inhibitor [6]
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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 [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 Enantioselective synthesis of (-)-englerins A and B. Angew Chem Int Ed Engl. 2010 May 3;49(20):3517-9.
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 (-)-Englerin is a potent and selective activator of TRPC4 and TRPC5 calcium channels. Angew Chem Int Ed Engl. 2015 Mar 16;54(12):3787-91.
5 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
6 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.
7 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.