Details of the Drug Combination

General Information of Drug Combination (ID: DCL0II0)

Drug Combination Name
Everolimus BMS-754807
Indication
Disease Entry Status REF
Embryonal rhabdomyosarcoma Investigative [1]
Component Drugs Everolimus   DM8X2EH BMS-754807   DMPK32V
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: Rh36
Zero Interaction Potency (ZIP) Score: 9.496
Bliss Independence Score: 9.687
Loewe Additivity Score: 8.604
LHighest Single Agent (HSA) Score: 9.288

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Everolimus
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [2]
Advanced/metastatic breast cancer 2C60 Approved [3]
Brainstem neoplasm N.A. Approved [2]
Breast carcinoma N.A. Approved [2]
Graft-versus-host disease 4B24 Approved [2]
Intracranial meningioma N.A. Approved [2]
Leukemia N.A. Approved [2]
Lung cancer 2C25.0 Approved [2]
Mucosal melanoma N.A. Approved [2]
Multiple sclerosis 8A40 Approved [2]
Plasma cell myeloma 2A83.1 Approved [2]
Prostate cancer 2C82.0 Approved [2]
Renal cell carcinoma 2C90 Approved [4]
Salivary gland squamous cell carcinoma N.A. Approved [2]
Tuberous sclerosis LD2D.2 Approved [2]
Kidney cancer 2C90.0 Phase 3 [4]
Castration-resistant prostate carcinoma N.A. Investigative [2]
Colon cancer 2B90.Z Investigative [2]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [5]
Neuroblastoma 2D11.2 Investigative [2]
Pancreatic acinar cell carcinoma N.A. Investigative [2]
Polycystic kidney disease GB8Y Investigative [2]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [5]
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 [6]
HUMAN mammalian target of rapamycin (mTOR) TT7HQAF MTOR_HUMAN Inhibitor [5]
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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 [7]
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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 [8]
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BMS-754807 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RAC-alpha serine/threonine-protein kinase (AKT1) TTWTSCV AKT1_HUMAN Inhibitor [9]
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BMS-754807 Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [10]
Insulin-like growth factor 1 receptor (IGF1R) OTXJIF13 IGF1R_HUMAN Decreases Phosphorylation [10]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [10]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Increases Response To Substance [10]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Response To Substance [10]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Response To Substance [10]
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⏷ Show the Full List of 6 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Embryonal rhabdomyosarcoma DC3IED4 CTR Investigative [1]
Embryonal rhabdomyosarcoma DCTADUS RD Investigative [1]
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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 Everolimus FDA Label
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 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).
5 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
6 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.
7 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.
8 The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.
9 Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in cli... J Med Chem. 2009 Dec 10;52(23):7360-3.
10 CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers. Cancer Res. 2014 Jul 15;74(14):3947-58. doi: 10.1158/0008-5472.CAN-13-2923. Epub 2014 Jul 1.