Details of the Drug Combination

General Information of Drug Combination (ID: DCY49EX)

Drug Combination Name
Ceritinib Ceritinib
Indication
Disease Entry Status REF
Embryonal rhabdomyosarcoma Investigative [1]
Component Drugs Ceritinib   DMB920Z 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: 17.332
Bliss Independence Score: 18.327
Loewe Additivity Score: 3.682
LHighest Single Agent (HSA) Score: 4.714

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Ceritinib
Disease Entry ICD 11 Status REF
Non-small-cell lung cancer 2C25.Y Approved [2]
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 [2]
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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 [3]
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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 [4]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [4]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [5]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [4]
Tyrosine-protein kinase JAK3 (JAK3) OTQ8QW2L JAK3_HUMAN Decreases Expression [4]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [4]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [4]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Affects Localization [4]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [4]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [4]
TNF receptor-associated factor 2 (TRAF2) OT1MEZZN TRAF2_HUMAN Decreases Expression [4]
Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) OTLUM9L7 PK3C3_HUMAN Decreases Expression [4]
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⏷ Show the Full List of 12 DOT(s)
Indication(s) of Ceritinib
Disease Entry ICD 11 Status REF
Non-small-cell lung cancer 2C25.Y Approved [2]
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 [2]
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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 [3]
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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 [4]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [4]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [5]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [4]
Tyrosine-protein kinase JAK3 (JAK3) OTQ8QW2L JAK3_HUMAN Decreases Expression [4]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [4]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [4]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Affects Localization [4]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [4]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [4]
TNF receptor-associated factor 2 (TRAF2) OT1MEZZN TRAF2_HUMAN Decreases Expression [4]
Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) OTLUM9L7 PK3C3_HUMAN Decreases Expression [4]
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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 DC6W1GN Rh36 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 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).
3 P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer. EBioMedicine. 2015 Dec 12;3:54-66.
4 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.
5 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.