Details of the Drug Combination

General Information of Drug Combination (ID: DCL2N4F)

Drug Combination Name
SCH772984 Ceritinib
Indication
Disease Entry Status REF
Embryonal rhabdomyosarcoma Investigative [1]
Component Drugs SCH772984   DMWVH62 Ceritinib   DMB920Z
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: RD
Zero Interaction Potency (ZIP) Score: 15.758
Bliss Independence Score: 16.379
Loewe Additivity Score: 5.879
LHighest Single Agent (HSA) Score: 7.02

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of SCH772984
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
SCH772984 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Extracellular signal-regulated kinase 2 (ERK2) TT4TQBX MK01_HUMAN Inhibitor [2]
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SCH772984 Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [4]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [4]
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Indication(s) of Ceritinib
Disease Entry ICD 11 Status REF
Non-small-cell lung cancer 2C25.Y Approved [3]
Ceritinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
ALK tyrosine kinase receptor (ALK) TTPMQSO ALK_HUMAN Modulator [3]
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Ceritinib Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [5]
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Ceritinib Interacts with 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ALK tyrosine kinase receptor (ALK) OTV3P4V8 ALK_HUMAN Decreases Phosphorylation [6]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [6]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [7]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [6]
Tyrosine-protein kinase JAK3 (JAK3) OTQ8QW2L JAK3_HUMAN Decreases Expression [6]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [6]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [6]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Affects Localization [6]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [6]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [6]
TNF receptor-associated factor 2 (TRAF2) OT1MEZZN TRAF2_HUMAN Decreases Expression [6]
Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) OTLUM9L7 PK3C3_HUMAN Decreases Expression [6]
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⏷ Show the Full List of 12 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Embryonal rhabdomyosarcoma DC4AXJX Rh36 Investigative [1]
Embryonal rhabdomyosarcoma DC8CEXO CTR Investigative [1]
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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 Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013 Jul;3(7):742-50.
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: 7397).
4 3,4,5-Tri-O-caffeoylquinic acid methyl ester isolated from Lonicera japonica Thunb. Flower buds facilitates hepatitis B virus replication in HepG2.2.15 cells. Food Chem Toxicol. 2020 Apr;138:111250. doi: 10.1016/j.fct.2020.111250. Epub 2020 Mar 7.
5 P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer. EBioMedicine. 2015 Dec 12;3:54-66.
6 1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)-3-(2-(dimethylamino)ethyl)imidazolidin-2-one (ZX-42) inhibits cell proliferation and induces apoptosis via inhibiting ALK and its downstream pathways in Karpas299 cells. Toxicol Appl Pharmacol. 2022 Sep 1;450:116156. doi: 10.1016/j.taap.2022.116156. Epub 2022 Jul 6.
7 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.