Details of the Drug Combination

General Information of Drug Combination (ID: DCF59TD)

Drug Combination Name
SCH 727965 Dexmedetomidine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs SCH 727965   DMCJLD1 Dexmedetomidine   DM93L4X
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 32.95
Bliss Independence Score: 32.95
Loewe Additivity Score: 45.34
LHighest Single Agent (HSA) Score: 45.35

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 [5]
Cyclin-dependent kinase 1 (CDK1) TTH6V3D CDK1_HUMAN Inhibitor [5]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [5]
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SCH 727965 Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [6]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [6]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Decreases Expression [7]
Breast cancer type 2 susceptibility protein (BRCA2) OTF1XSV1 BRCA2_HUMAN Decreases Expression [7]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Decreases Expression [7]
Fanconi anemia group D2 protein (FANCD2) OTVEB5LF FACD2_HUMAN Decreases Expression [7]
Cyclin-dependent kinase 12 (CDK12) OTZUDGNU CDK12_HUMAN Decreases Activity [7]
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⏷ Show the Full List of 7 DOT(s)
Indication(s) of Dexmedetomidine
Disease Entry ICD 11 Status REF
Irritability MB24 Approved [3]
Obstructive sleep apnea 7A41 Approved [4]
Traumatic brain injury NA07.Z Approved [4]
Respiratory failure CB41 Investigative [4]
Dexmedetomidine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor Alpha-2 (ADRA2) TTQ8AFT NOUNIPROTAC Agonist [8]
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Dexmedetomidine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [9]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [10]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [11]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
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 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: 521).
4 Dexmedetomidine FDA Label
5 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
6 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.
7 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.
8 Dexmedetomidine in intensive care unit: a study of hemodynamic changes. Middle East J Anesthesiol. 2002 Oct;16(6):587-95.
9 Predominant role of peripheral catecholamines in the stress-induced modulation of CYP1A2 inducibility by benzo(alpha)pyrene. Basic Clin Pharmacol Toxicol. 2008 Jan;102(1):35-44.
10 Impact of CYP2A6 gene polymorphism on the pharmacokinetics of dexmedetomidine for premedication. Expert Rev Clin Pharmacol. 2018 Sep;11(9):917-922.
11 Metabolic stability and determination of cytochrome P450 isoenzymes' contribution to the metabolism of medetomidine in dog liver microsomes. Biomed Chromatogr. 2010 Aug;24(8):868-77.