Details of the Drug Combination

General Information of Drug Combination (ID: DCR4X1T)

Drug Combination Name
Evacetrapib SCH 727965
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Evacetrapib   DMCDZ15 SCH 727965   DMCJLD1
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DIPG25
Zero Interaction Potency (ZIP) Score: 9.08
Bliss Independence Score: 7.015
Loewe Additivity Score: 4.576
LHighest Single Agent (HSA) Score: 9.009

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Evacetrapib
Disease Entry ICD 11 Status REF
Cardiovascular disease BA00-BE2Z Phase 3 [2]
Evacetrapib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cholesteryl ester transfer protein (CETP) TTFQAYR CETP_HUMAN Inhibitor [4]
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Evacetrapib Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [5]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [5]
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Indication(s) of SCH 727965
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Discontinued in Phase 3 [3]
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 [6]
Cyclin-dependent kinase 1 (CDK1) TTH6V3D CDK1_HUMAN Inhibitor [6]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [6]
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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 [7]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [7]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Decreases Expression [8]
Breast cancer type 2 susceptibility protein (BRCA2) OTF1XSV1 BRCA2_HUMAN Decreases Expression [8]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Decreases Expression [8]
Fanconi anemia group D2 protein (FANCD2) OTVEB5LF FACD2_HUMAN Decreases Expression [8]
Cyclin-dependent kinase 12 (CDK12) OTZUDGNU CDK12_HUMAN Decreases Activity [8]
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⏷ Show the Full List of 7 DOT(s)

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: 8401).
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: 7379).
4 The dyslipidaemia market. Nat Rev Drug Discov. 2014 Nov;13(11):807-8.
5 Identification of cytochrome P450 enzymes involved in the metabolism of 4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), a designer drug, in human liver microsomes. Xenobiotica. 2003 Oct;33(10):989-98.
6 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
7 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.
8 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.