Details of the Drug Combination

General Information of Drug Combination (ID: DCR0X34)

Drug Combination Name
LEE011 Everolimus
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs LEE011   DMMX75K Everolimus   DM8X2EH
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: 1.976
Bliss Independence Score: 4.704
Loewe Additivity Score: 3.696
LHighest Single Agent (HSA) Score: 3.709

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of LEE011
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 3 [2]
Solid tumour/cancer 2A00-2F9Z Phase 3 [3]
LEE011 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 4 (CDK4) TT0PG8F CDK4_HUMAN Modulator [8]
Cyclin-dependent kinase 6 (CDK6) TTO0FDJ CDK6_HUMAN Modulator [8]
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LEE011 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [9]
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Indication(s) of Everolimus
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [4]
Advanced/metastatic breast cancer 2C60 Approved [5]
Brainstem neoplasm N.A. Approved [4]
Breast carcinoma N.A. Approved [4]
Graft-versus-host disease 4B24 Approved [4]
Intracranial meningioma N.A. Approved [4]
Leukemia N.A. Approved [4]
Lung cancer 2C25.0 Approved [4]
Mucosal melanoma N.A. Approved [4]
Multiple sclerosis 8A40 Approved [4]
Plasma cell myeloma 2A83.1 Approved [4]
Prostate cancer 2C82.0 Approved [4]
Renal cell carcinoma 2C90 Approved [6]
Salivary gland squamous cell carcinoma N.A. Approved [4]
Tuberous sclerosis LD2D.2 Approved [4]
Kidney cancer 2C90.0 Phase 3 [6]
Castration-resistant prostate carcinoma N.A. Investigative [4]
Colon cancer 2B90.Z Investigative [4]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [7]
Neuroblastoma 2D11.2 Investigative [4]
Pancreatic acinar cell carcinoma N.A. Investigative [4]
Polycystic kidney disease GB8Y Investigative [4]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [7]
Everolimus Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [10]
HUMAN mammalian target of rapamycin (mTOR) TT7HQAF MTOR_HUMAN Inhibitor [7]
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Everolimus Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]
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Everolimus Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [12]
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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 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 7383).
4 Everolimus FDA Label
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6 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: 5889).
7 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
8 Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
9 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
10 Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
11 Closer to the Site of Action: Everolimus Concentrations in Peripheral Blood Mononuclear Cells Correlate Well With Whole Blood Concentrations. Ther Drug Monit. 2015 Oct;37(5):675-80.
12 The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.