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

2D MOL

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 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tyrosine-protein kinase JAK3 (JAK3)	OTQ8QW2L	JAK3_HUMAN	Decreases Expression	[6]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[6]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Affects Localization	[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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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	CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
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.