Details of the Drug Combination

General Information of Drug Combination (ID: DC436QT)

Drug Combination Name

Everolimus Cotellic

Indication

Disease Entry	Status	REF
Embryonal rhabdomyosarcoma	Investigative	[1]

Component Drugs

Everolimus DM8X2EH

Cotellic DMF9M57

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: CTR

Zero Interaction Potency (ZIP) Score: 2.556

Bliss Independence Score: 2.454

Loewe Additivity Score: 10.982

LHighest Single Agent (HSA) Score: 11.503

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	[9]
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	[10]
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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	[11]
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Indication(s) of Cotellic

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Phase 3	[6]
Breast cancer	2C60-2C65	Phase 2	[7]
Head and neck cancer	2D42	Phase 1	[7]
Renal cell carcinoma	2C90	Phase 1	[7]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
Urothelial carcinoma	2C92.0	Phase 1	[7]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Embryonal rhabdomyosarcoma	DCLBUJD	Rh36	Investigative	[1]
Embryonal rhabdomyosarcoma	DC14076	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	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
7	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8	ClinicalTrials.gov (NCT01106599) A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0623 in Patients With Locally Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health.
9	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.
10	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.
11	The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.