Details of the Drug Combination

General Information of Drug Combination (ID: DCY6LK5)

Drug Combination Name
ZM-447439 Thiolactomycin
Indication
Disease Entry Status REF
Hepatoblastoma Investigative [1]
Component Drugs ZM-447439   DMFP8WE Thiolactomycin   DMBAWDG
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: 5.568
Bliss Independence Score: 6.439
Loewe Additivity Score: 0.961
LHighest Single Agent (HSA) Score: 1.573

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of ZM-447439
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
ZM-447439 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [5]
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ZM-447439 Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Neurogenic locus notch homolog protein 1 (NOTCH1) OTI1WADQ NOTC1_HUMAN Increases Expression [6]
Aurora kinase B (AURKB) OTIY4VHU AURKB_HUMAN Affects Localization [7]
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Indication(s) of Thiolactomycin
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Investigative [3]
Urinary tract infection GC08 Investigative [4]
Thiolactomycin Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial Beta-ketoacyl-ACP synthase I (Bact fabB) TT0O4QL FABB_ECOL6 Binder [3]
Plasmodium Enoyl-ACP reductase (Malaria fabI) TTNX2CS Q965D5_PLAFA Inhibitor [8]
Bacterial Beta-ketoacyl-ACP synthase III (Bact fabH) TTRVTMX FABH_ECOLI Binder [9]
Bacterial Oxoacyl-[acyl-carrier-protein] synthase II (Bact fabF) TTRFV0W FABF_ECOLI Binder [3]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
DD2 DCYY8PA DD2 Investigative [10]
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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: 8353).
3 Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
4 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
5 Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring. J Med Chem. 2006 Aug 10;49(16):4805-8.
6 PLK1 targets NOTCH1 during DNA damage and mitotic progression. J Biol Chem. 2019 Nov 22;294(47):17941-17950. doi: 10.1074/jbc.RA119.009881. Epub 2019 Oct 9.
7 DNA double-strand breaks and Aurora B mislocalization induced by exposure of early mitotic cells to H(2)O(2) appear to increase chromatin bridges and resultant cytokinesis failure. Free Radic Biol Med. 2017 Jul;108:129-145. doi: 10.1016/j.freeradbiomed.2017.03.025. Epub 2017 Mar 24.
8 Novel molecular targets for antimalarial drug development. Chem Biol Drug Des. 2008 Apr;71(4):287-97.
9 The apicoplast as an antimalarial drug target. Drug Resist Updat. 2001 Jun;4(3):145-51.
10 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.