Details of the Drug Combination

General Information of Drug Combination (ID: DC09KZR)

Drug Combination Name
(-)-englerin A Daporinad
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs (-)-englerin A   DMPQBWY Daporinad   DMCU74R
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: 13.989
Bliss Independence Score: 13.15
Loewe Additivity Score: 2.819
LHighest Single Agent (HSA) Score: 7.494

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 Daporinad
Disease Entry ICD 11 Status REF
leukaemia 2A60-2B33 Phase 2 [3]
Daporinad Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Nicotinamide phosphoribosyltransferase (NAMPT) TTD1WIG NAMPT_HUMAN Inhibitor [5]
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Daporinad Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Axin-1 (AXIN1) OTRGZGZ5 AXIN1_HUMAN Increases Expression [6]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [6]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [6]
Nicotinate phosphoribosyltransferase (NAPRT) OTVVN0SL PNCB_HUMAN Decreases Activity [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: 7745).
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 Anticancer agent CHS-828 inhibits cellular synthesis of NAD. Biochem Biophys Res Commun. 2008 Mar 21;367(4):799-804.
6 Targeting the NAD(+) salvage pathway suppresses APC mutation-driven colorectal cancer growth and Wnt/-catenin signaling via increasing Axin level. Cell Commun Signal. 2020 Jan 31;18(1):16. doi: 10.1186/s12964-020-0513-5.
7 FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res. 2003 Nov 1;63(21):7436-42.