Details of the Drug Combination

General Information of Drug Combination (ID: DCM1EIT)

Drug Combination Name
SCH 727965 CYTISINE
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs SCH 727965   DMCJLD1 CYTISINE   DMUF0BJ
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SU-DIPG-XIII
Zero Interaction Potency (ZIP) Score: 20.97
Bliss Independence Score: 21.696
Loewe Additivity Score: 7.948
LHighest Single Agent (HSA) Score: 8.013

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 [4]
Cyclin-dependent kinase 1 (CDK1) TTH6V3D CDK1_HUMAN Inhibitor [4]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [4]
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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 [5]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [5]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Decreases Expression [6]
Fanconi anemia group D2 protein (FANCD2) OTVEB5LF FACD2_HUMAN Decreases Expression [6]
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Indication(s) of CYTISINE
Disease Entry ICD 11 Status REF
Tobacco dependence 6C4A.2 Phase 3 [3]
CYTISINE Interacts with 6 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Neuronal acetylcholine receptor alpha-7 (CHRNA7) TTLA931 ACHA7_HUMAN Inhibitor [7]
Neuronal acetylcholine receptor alpha-2 (CHRNA2) TTF4E0J ACHA2_HUMAN Inhibitor [8]
Neuronal acetylcholine receptor alpha-4 (CHRNA4) TT4H1MQ ACHA4_HUMAN Inhibitor [9]
Neuronal acetylcholine receptor beta-4 (CHRNB4) TTTVAFQ ACHB4_HUMAN Inhibitor [10]
Nicotinic acetylcholine receptor (nAChR) TTJSZTB NOUNIPROTAC Antagonist [3]
Neuronal acetylcholine receptor beta-2 (CHRNB2) TT5KPZR ACHB2_HUMAN Inhibitor [9]
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⏷ Show the Full List of 6 DTT(s)

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 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
5 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.
6 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.
7 3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation. Bioorg Med Chem Lett. 2005 Nov 15;15(22):4889-97.
8 Synthesis and pharmacological evaluation of novel 9- and 10-substituted cytisine derivatives. Nicotinic ligands of enhanced subtype selectivity. J Med Chem. 2006 May 4;49(9):2673-6.
9 Epibatidine isomers and analogues: structure-activity relationships. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5493-7.
10 Deconstructing cytisine: The syntheses of (+/-)-cyfusine and (+/-)-cyclopropylcyfusine, fused ring analogs of cytisine. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2316-9.