Details of the Drug Combination

General Information of Drug Combination (ID: DC5UH2Y)

Drug Combination Name
SCH 727965 PMID28870136-Compound-43
Indication
Disease Entry Status REF
Glioma Investigative [1]
Component Drugs SCH 727965   DMCJLD1 PMID28870136-Compound-43   DMWGV8N
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SF-295
Zero Interaction Potency (ZIP) Score: 0.49
Bliss Independence Score: 2.65
Loewe Additivity Score: 1.72
LHighest Single Agent (HSA) Score: 1.43

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of SCH 727965
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Discontinued in Phase 3 [2]
SCH 727965 Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 9 (CDK9) TT1LVF2 CDK9_HUMAN Inhibitor [3]
Cyclin-dependent kinase 1 (CDK1) TTH6V3D CDK1_HUMAN Inhibitor [3]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [3]
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SCH 727965 Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [4]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [4]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Decreases Expression [5]
Fanconi anemia group D2 protein (FANCD2) OTVEB5LF FACD2_HUMAN Decreases Expression [5]
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PMID28870136-Compound-43 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Ecto-5'-nucleotidase (CD73) TTK0O6Y 5NTD_HUMAN Inhibitor [6]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Clear cell renal cell carcinoma DCRJJ10 TK-10 Investigative [1]
Breast adenocarcinoma DCHOQ4Q MDA-MB-468 Investigative [7]
Adenocarcinoma DC1JR95 HCT-15 Investigative [8]
High grade ovarian serous adenocarcinoma DC4MNJ9 OVCAR-4 Investigative [8]
Ovarian serous cystadenocarcinoma DCRDV2Q SK-OV-3 Investigative [8]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
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: 7379).
3 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
4 Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010 Aug;9(8):2344-53. doi: 10.1158/1535-7163.MCT-10-0324. Epub 2010 Jul 27.
5 CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer. Cell Rep. 2016 Nov 22;17(9):2367-2381. doi: 10.1016/j.celrep.2016.10.077.
6 Ectonucleotidase inhibitors: a patent review (2011-2016).Expert Opin Ther Pat. 2017 Dec;27(12):1291-1304.
7 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
8 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976